u of wm tom yin grant documents part 2

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*************.**************** NOTICE OF GRANT AWARD* * * * * * * * * * * * * * * * ~ * * * * * * * * * * * RESEARCH I s sue Date: 03/01/2001Department of Heal th and Human Serv icesNat ional I n s t i t u t e s Of HealthNATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS********************************************************************************

Grant Number: 2 R01 DC02840-06Pr i n c i p a l Inves t iga tor : YIN, TOM C PHDPro j ec t T i t l e : BEHAVIORAL & PHYSIOLOGICAL STUDIES OF SOUND LOCALIZATION

ADMIN OFFICERUNIVERSITY OF WISCONSINRES & SPON PRAG, PETERSON BLDG75 0 UNIVERSITY AVE, 4TH FLMADISON, WI 53706-1490

Budget Period: 03/01/2001 - 02/28/2002Pro j ec t Period: 03/01/1996 - 02/28/2006

Dear Business Off ic ia l :The Nat ional I n s t i t u t e s of Heal th hereby awards a gran t in th e amount of$216,996(see "Award Calculat ion" in Sect ion I) to UNIVERSITY OFWISCONSIN MADISON in suppor t of th e above r eferenced pr o jec t . Thisaward i s pursuan t to the au thor i ty of 42 USC 24 1 42 CFR 52 and i ssub jec t to te rms and condi t ions re ferenced below.Acceptance of th i s award including th e Terms and Condi t ions i sacknowledged by the gran tee when funds a re drawn down or otherwiseobta ined from the g ran t payment system.Award r ec ip i en t s a r e responsible fo r repor t ing inven t ions der ived orreduced to p r a c t i c e in the performance of work under t h i s gran t . Rightsto inven t ions ves t with the gran tee o rgan iza t ion provided cer ta inrequirements a re met and there i s acknowledgement of NIH suppor t . Inadd i t ion , r ec ip ien t s must ensure t h a t p a t en t and l i cense a c t i v i t i e s a recons i s t en t with t h e i r r espons ib i l i ty to make unique r esearch resourcesdeveloped under t h i s award ava i l ab le to th e sc i e n t i f i c community, inaccordance with NIH pol icy . For add i t iona l in format ion , please v i s i tht tp : / /www. ied ison .gov .I f you have any quest ions about t h i s award, please contac t theind iv idual (s ) r eferenced in th e in format ion below.

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Sincere ly yours ,

Meigs RanneyGrants Management Off i ce rNATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

See add i t i ona l in format ion below

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SECTION I - AWARD DATA - 2 R01 DC02840-06AWARD CALCULATION (U.S. Dol lars ) :Di rec t CostsF&A CostsAPPROVED BUDGETTOTAL

$159,250$57,746$216,996$216,996

Recommended fu tu re year t o t a l cos t suppor t , sub jec t to the a v a i l a b i l i t yof funds and s a t i s f a c t o r y progress o f the pro jec t , i s as fol lows.07 $198,60808 $198,60809 $198,60810 $198,608

FISCAL INFORMATION:CFDA Number 93.173

DocumentIC / CAN Number: R1DC02840B/ FY2001 / FY2002 / FY2003 / FY2004 /DC/8424501/198,608 216,996/ 198,608/ 198,608/ 198,608/

NIH ADMINISTRATIVE DATA:PCC: HR02 / OC: 41.4B /Processed: MRANNEY 010227 0926Award e-mai led to: [email protected]

SECTION I I - PAYMENT/HOTLINE INFORMATION - 2 R01 DC02840-06

FY2005

For Payment and HHS Off ice of Inspec to r General Hotl ine Informat ion,see th e NIH Horne Page a tht tp : / /g ran t s .n ih .gov /gran t s /po l i cy /awardcondi t ions .h tmSECTION I I I - TERMS AND CONDITIONS - 2 R01 DC02840-06This award i s based on the appl ica t ion submit ted to , and as approved by,th e NIH on the above - t i t l ed p r o j ec t and i s sub jec t to th e terms andcondi t ions incorpora ted e i t h e r d i r e c t l y or by re ference i n th efol lowing:a . The g ran t program l eg i s l a t ion and program regu la t ion c i t ed in th i s

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Notice of Grant Award.b. The r es t r i c t ions on the expendi tu re of federa l funds inappropr ia t ions a c t s , to the ex ten t those r e s t r i c t i o n s a re p e r t i n e n t tothe award.c. 45 CFR Par t 74 o r 45 CFR Par t 92 as ap p l i cab l e .d. The NIH Grants Pol icy Sta tement , inc lud ing addenda in e f f e c t as ofthe beginning date o f the budget p er io d .e . This award not i ce , INCLUDING THE TERMS AND CONDITIONS CITED BELOW.(see NIH Home Page a t

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h t t p : // g r an t s .n i h .g o v / g ran t s / p o li cy / aw ard co n d i t i o n s .h t m fo r ce r t a inre ferences c i t e d above.}

This gran t i s awarded under the t erms and condi t ions o f the FederalDemonstrat ion Par tnersh ip Phase I I I .

This g ran t i s sub jec t to Streamlined Noncompeting Award Procedures

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(SNAP) .

Treatment of Program Income:Addit ional CostsThis i s a Modular Grant Award withou t d i r e c t c o s t ca tegor ica l breakdownsin accordance with guide l ines publ ished in the 12/15/98 NIH Guide fo rGrants and Contrac ts , we b address:ht tp : / / g r an t s . n ih .gov /g r an t s /gu ide /no t i ce - f i l e s /no t98- 178 .h tml .Recipients are requ i red to a l loca te and account for cos ts r e la ted toth i s award by category with in t h e i r i n s t i t u t i o n a l account ing system i naccordance with app l icab le cos t pr inc ip les . The s i g n i f i c a n t rebudget ingprov i s ion does not apply to Modular Grant Awards. Therefore, futurenoncompeting SNAP appl ica t ions should i nd ica t e "N/A" fo r ques t ion number(2 ) regarding s i g n i f i c a n t rebudget ing.

Program Contact : Dr. Lynn Luethke 301/402-3458Grants Management: 301/402-0909

LYNN LUETHKE, Program Off ic ia l (301) 402-3458 LYNN [email protected] Chicch i r i ch i , Grants S p e c i a l i s t 30 1 [email protected] .gov

SPREADSHEETGRANT NUMBER: 2 ROl DC02840-06P . I . : YIN, TOM CINSTITUTION: UNIVERSITY OF WISCONSIN MADISON

YEAR 06 YEAR 07 YEAR 08 YEAR 09 YEAR 10========= ========= ========= ========= =========

TOTAL DC 159,250 136,500 136,500 136,500 136,500TOTAL F&A 57,746 62,108 62,108 62,108 62,108TOTAL COST 216,996 198,608 198,608 198,608 198,608

YEAR 06 YEAR 07 YEAR 08 YEAR 09 YEAR 10========= ========= ===::::::::::::::::::: ========= ::::=:::======

F&A Cost Rate 1 45.50% 45.50% 45.50% 45.50% 45.5{)%

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F&A Cost Base 1F&A Costs 1

126,91557,746

136,50062,108

136,50062,108

136,50062,108

136,50062,108

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11/29/2010 0'3:39f32 ...e3r"'200:3 '09: 01 PAGE 01/04I ' I U . ~ : L . L \"Fr,o!U,l..

Unlversity of W j s c o n s i n ~ M a . d i s o n Graduate School, Research and Sponsored ProgramsFax Cover SheetTo:Company:Telephone:Fax:From:Date:Total Pages:SUbject:Comments:

Hoal Doan, Grants Management SpecialistN1H/NIDCO/OERIGMB301/402-0909301f4021758

~ . J 3 J 2 0 0 3 * 135 R01 DC028400B/PI: Tom C. T. YinPlease see the attached in response to your reCluest of 1/30/03.[ .j

,* " t \ ~ CorJo.d ~ o r t ' Y ' ( ' . ~ ~ ~ ~ 0 ~ -} ] ! . - - - . ~ .. ~ - - -A:- ' .. . ' -- ]11/29/2-010 9:52AM (GMT-{)5:00)

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11/29/2010 09:391il2?'0J,'2Ofl3 0,): 01 3014021758 NIDCD tUW ~ S E A R C H AND SPONSDRF;n PRGRMS _---'7C!.r__

Hoa! DoanGra.uts Management SpecialistNIBlNIDCPIPBRlGMB6120 ~ u t i v e Blvd,Su,(te 400C, MSC 7180Rockville, MIl 20852Dear'Mr;, Dean,

DNCVE1l5J1YOfWJSCONSlN-MADlSONMEDICAL SCHOOL

January :31, 2003

Please find attaohed the CUt't$1).t IACUC approval for Dr. Tom. c:r. Yin's grmt

PAGE 02/04l'iU. ~ J . . t : l " ~ . c .

5 ROI PC(l2840..oo entitled, "Behavioral and Physiologioal Studies of Sound Looalization", I fyou ha ...e UJ.y q u e s ~ o n s , please do not hesi'W.e to contactme.

\ . _ ~ J

6 ~ 1 - ~ ~ O Q / a O O ' d ~ Z t - 1 AD010ISAH


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,

11/29/2010 09:39B2/03/20e3 09=01

3014021758 NIDCD; 1UNIVERSITY O fWISCONSINMADISON-

TO WHOM IT MAY CO;NCSRN:

,-._.

The following applioation submitted to NJH was receivedby tWs Animal Care Committee (Ace) and IIpJ;lroved on 1"'02/2002.(3 year approval)Most recent committee r",-revlew: 1210212002.NallJe of Principal Investigator: Yin, Tom C.T.Add.tess; 290 MSC

12110/2002

Title of Application: Behavioral and Physiological Studies of Sound Locallzatj(lUOranti: DC02B40Name of Animal ear" Committee: MSCName of Chllirperson: Dr. JlU'lles Sou!11atd

PAGE 03/04

The. Unlversit)' of Wisconsin-Madison has an animal welfare assurance on file with the Office fot'l."roteotlQll from Rl)sca.rch :Risks. The Msurano/l number A3368-01.

Signlfieant mod!.ficiltions requlNld prior to comm.tttce approval of Il. protQ


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....

11/29/2010 09:39 3014.021758 NIDeD

-. N YE RSIT Y 0 FWISCONSINMADISON

01125/2000TO WHOM IT MAY CONCERN:The following upplicatilln submitted to NIH was receivedby this Animlll Care Committee (ACC) lind nppmved on 01/04/2000.Current Annual Re-approval date: 01/04/2000.No.roe of Principal InvestIgator: Yin, Tom c:r.Ad(\ress: 290 MSC

Tille of Application: Behavioral and Physiological S t u d i e . ~ of Sound LocnlizationGrant #; 1 ROI DC0284()Nume of Animal Care Committee: MSCName ofChaltpcrsoo: Pro James SllUlIWd

PAGE 04/041-IJ.585 Rllil2

The University of Wisconsin-Madison hils lIllllnimul welfare assul'llIIce on file with rhe Oftice forProtection from Research Risks. The 3!sUIllnce number is A:3368-01.

Significant modifications required prior to committee approval of a protocol w 'eh was alreadysubmitted to the funding agency ill'll us follows: NONE

Chairperson's Signature:__ . . ; d ; . _ ~ ~ . ~ ~ _ ...__-__FORM / I M O O 2 1 2 ~ 1 2 9 ~

Research Animal Resour


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'BID1AA 8 0 2 5 3 5 NAME: YIN,TOMf' IAPPL NO:2 R01 DC0284006 COUNCIL: 1000DUAL: RCVD:030100IRG: ZRG1IFCN6(1S)U ' d i l l 1"\..,..,.....amIiF .


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BB _ _. _ . _ ~ _____ .__ ..___.~ - " ' . l l n v e s l ~ . I ~ r / P r o ~ ~ ~ ~ r e c t o r l ! - a s t ! r s t , ~ . yin!. T o ~ ~ : . : ' __. _: :==.=DESCRIPTION. State the application's broad, long-term objectives and specific alms, making reference to the health relatedness of the project. Describecondsely the research design and methods for achievinglhese goals. Avoid summaries of past accomplishments and the use of the first person.This description ismeanllo serve .s asucctnct and accur.le description ollhe proposed work when separated from !he applicalion. If he application is fUnded.lhis description. as Is.will become public infoonalion. Therefore. do nollndude proprielary/conlidenllallnfonnallon. DO NOT EXCEED THE SPACE PROVIDED.

The long-tenn objective of this project IS a thorough understandmg of the behavioral and neural mechan1sms of Isound localization. Previous studies of sound localization have chiefly centered on two areas: human and animal ,psychophysical work has established the important cues for localization while animal physiological work h a ~ shown the neural mechanisms by which the auditory system encodes these cues. This application is an effort to Ilink these two approaches by combining animal psychophysics with physiology. This application proposes toextend our present behavioral preparation for testing sound localization in cats by freeing the head of the cat sothat it can orient to the sound with unrestrained head and/or eye movements. In addition we will continue ourphysiological studies of sound localization by recording from cells during this behavior.There are two general specific aims: one directed to behavior and the other to physiology. Specific aim I willdevelop the head-free preparation by monitoring eye, head and ear movement using the search coil technique andstandard operant conditioning. We will compare the accuracy of localization in the head-fixed and head-freeconditions, study the effect of spectral cues on localization by narrowband pass filtering noise stimuli, andexamine the role of pinna movements by studying the movements of the pinna as well as the effect on localizationability of paralyzing the pinna muscles. Specific aim II is aimed at physiological recordings in these animals iwhile they are actively localizing sounds. We will continue our examination of the motor error hypothesis by I, recording in the superior colliculus and studying the effect of eye position on auditory responses. Then we Ipropose to move to the auditory cortex where we expect to find cells whose response properties are correlatedwith the behavioral localization of the stimulus. By progressively narrowband pass filtering the noise stimulus,! we expect the cat to gradually mislocalize the sound. At some point the cat will be near threshold, looking half thetime at the proper location and the other half to some phantom location. At this point we can deliver the identicalstimulus with two different behaviors and correlate the neural activity to one behavior or another.. Spatial hearing and sound localization are important basic functions of the auditory system: defects in binaural: function in human patients can lead to considerable difficulty in detecting signals embedded in noise, such asi understanding conversations in a crowded room, which is perhaps the most common complaint of the hearing; impaired and can lead to severe social withdrawal.

-PERFORMANceSft-g(S)(organlzalion, c:ify iii,r-------University of WisconsinMadison, WI

..... - ... ----....- - - - ~ - --..-.-...---...- ..- . - . - ...- ~ - ~ - .. . . __ .. . .. -- .. ~ - . - -KEY PERSONNEL. See Instrudions on Page 11. Use oonMustionPIlfI6S 8S n86d6d to provide Ihe required Infonnalion in !he fonnat shown below.Name Organization Ro)e on Projed

.- ,

Tom C.T. Yin___ _ _ _ _Unive.r$lty ofWiscO!lin-Madis.on____ __ :'..L_____ _...

PHS 398{Rev. 4198) Page2 BBNumber pages consecutively at the bottom throughout the application. Do wause suffixes such as 3a, 3b.

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cc erinCiPallnVeSllgatotJProgramDirector (L8St, first,m. _.Yill . Iom=C=.T=,.=----:':...:,'...ccc_.---_-_._.Type the name of the principal investigator/program director at the top of each printed page and each continuation page. (For type specifICations, see instructionson page S.)

RESEARCH GRANTTABLE OF CONTENTS

Face Page , . . . . II II.'.' ". II II . I. ' to . , , II " , II ,. II .Description. Performance Sites, and Personnel . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . .. . . . . . . Table ofContents .. ", . " .. " .. , . . . . "',',',', . , .. ,","""", . " . . . . " . . . . , ', .. ,',"", . ,",', . , ' .. ,",',',", .Detailed Budget forlnilial Budget Period ' , , , , , .. , , , , , , , , , , , .. , , , , , . . . . , , , . . . . , , . . . . . . . . , , , , , , , , , , .. , , , , , .. , , .. , , , , , .. , , , , ,Budget for Entire Proposed Period of Support' , . . . . , , . . . . . . , .. , , , , , .. , .. , , .. , , .. , .. , . . . . , , , , , , , , , , .. , , , , .. , , , , , , , , . . . . . . ..Budgets Pertaining to ConSl>rtiunVContractual Arrangements ' , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,Biographical Sketch,PrincipallnvestIgator/Program Director (Nolfo .xcoed twopages) , , , , , , " , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,other Biographical Sketches (Not to.xcoed twopages foraach) , , .. , , .. , , , , .. , .. , .. , , , , .. , , .. , ,.. , , , , , , , , , , , , , , , , .. , , , .... ,other Support ", . , " , . . . . , .. ', .. , .. ,""', . "', . , .. , ' . . . . . " .. , '" .. ', .. " . . . . ", . ,',"', . , , ' , .. , ' .. "' , . " .. , ..Resources ............. , . I I I, . ,. ,

Research PlanIntroduction to Revised Application (No! fo excoed3pages) , , .. , , , ...... , .... , .. , , , ...... , .. , , , , , .. , .... , , , , .. , , , , .. , , , , .. , ,t n ~ o d u c t i o n to Supplemental Application (Not to axcoed 1page) , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

a, SpacificAlms . . . . . . . . . . . . . . . . . . . . . .}""" ,. " .. , ' , .. , ' , .. , ' , . . . . . . .. , ' , .. , ' . . . . . . . . , .. ,",', . ", . ", . " "b. Background and Significance ' , , , .. , " "',",', . , .. "' , . ", . . . . . . . , ' , .. , . . . . ,"""", . , .. ,"' . ,, .. ,"", . ,c. Preliminary Studiesl?rogress Report , . . l ~ t ~ ' ! ! ~ ~ ~ f : . '!'!t. t,o. ~ ~ < : ' 1 f ! ' ! . ~ ~ ~ ~ ~ .................. , ..................... .d, Research Design and Methods ,"",' , , , , , , " , ", , " , , , " , ,, " ' , , , , ' " , , , , , , " , , , , , , " , " , , , '" , , , , " , " , , , " "e. Hum an Subjeds . . . . . . . . . . . . . . . . , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1. Vertebrate Animals . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . g. Literature Cited .. , . . . . . . . . . . . . . . , . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . . ..h. ConsortlutniContractuaiArrsng8ftlElnts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i. Consultants . . . . . . . . . . . , . .. . . . . ......... . .. . . . . . .. . . . . . .. . .. . . . . . . . . . . . . . . . . . . . . .. . . . . . . .

Checklist""' , .. , . . . . , . . . . , . . . . . . . . ,""""""", . , .... ,, .. , .. , .. ,' . . . . , .. , , ' .. ,"', . ," , . ,"""""', . , ' , . . . .*Type density and type size of the entire appllcaUon must confonn to limns provkfed 10 instructions on page 6.

Page Numbers

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Appendix (Five coIlaled sats. No page numbering naCOSS81)1 forAppendix.)Number of publication. and manuscripts acoopted or submitted for publication (not fo axcoed 10)Othar nems (lisl):

6 CheckffAppandixlsincluded

PHS 398 (Rev. 4198) (Form Page 3) Page.......3-. CCNumber pages consecutively at the Mllom lhroughout the application. Do nat use suffIXes such as 3a. 3b.

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eincipallnvestlgatorlPrOgram Direct.rILa.t, first, mi. Yin'c,T=o=m=,=C=,=T=,=_=. =.=_oc_c. c_=_ .. _

BUDGET JUSTIFICATION PAGE:MODULAR RESEARCH GRANT APPLICATION

Total Direct Costs for Entire Proposed Period of Support: $775,000

PersonnelTom C.T. Yin, Ph.D., Principal Investigator CO% effort) is responsible for the scientific directionof the projects and wil,l participate in all phases of it, including: designing the experiments, collecting andanalyzing the data, and writing up the results, To give students and post-docs the experience in designing andrunning experiments, they are usually assigned primary responsibility for one project This means theyschedule experiments, are responsible for making sure that all of the necessary hardware, software and otheraspects of the experiment are ready, direct the activitites of other personnel involved in the project, make themajor decisions during the execution of the experiments, decide how to analyze the data, do the bulk of the dataanalvsis. and write the first draft of the manuscrint All of this is done in consultation with the P.Lr 4 ' :J. Ph.D., Research Associate (>% effort) joined. the lab as a post-doctoral fellow" ,(,'He is responsible for the surgical preparallon and training of the behavioral animals and all aspects ofdata collection, analysis and write-up of the behavioral experiments. In addition he participates actively in theelectrophysiological recordings from the superior colliculus, inferior colliculus and cortex.r} s \ , Assistant Scientist


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.ncipallnve,tlgaloilPtOQtamOlteclot (Last, first, m i. YinLTom C.T,

To complete our second coil system, we are requesting a phase angle search coil system from CNCEngineering, We already have the 5' coil frame fabricated with p h a ~ e angle coils so we only need theelectronics (power driver and three phase detectors (for eye, head and ear coils) at $19,978, The phase anglesearch coil system allows measurements out to large eccentric angles without substantial non-Iinearities,The purchase of the above items will increase the requested budget for the firSt year by one module ($25,000).*The Medical School Research Committee will provide one-third (1/3) of the funds for thepurchase of the equipment referenced above if the federal granting agency provides theremaining two-thirds (2/3). The price quoted in the federal grant application for this itemreflects this matching award by requesting two-thirds of the estimated cost

.------- - - - - - - - - _ . _ - - - - - - -PHS 398 (Rev_ 4198) Page - . -LNumbet page consectrtively allhe boIIom ollila application. Do 0Ql use suffixes sucI1 as 30, 3b.----------- .... ---- .._----2011-04-22 000097


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Tom Yin, ProfessorDepartment of Physiology121 SMI -Madison, WI 53706Dear Dr. Yin:

UNIVERSITY OFWISCONSIN-MADISON

MEDICAL SCHOOL

February 23, 2000

I am delighted to confirm the support of the Medical School towards your NationalInstitutes of Health proposal entitled, "Behavioral and Physiological Studies of SoundLocaHzation", by providing 113 of the cost of a sound proofroo1n if the sponsor providesthe remaining 2/3. The estimated cost is $42,160 so the sponsor's portion would be$28,107 and the Medical School portion would be $14,053. The price used in the budgetpreparation reflects this matching award. The proposed equipment will certainly be aninvaluable acquisition to the stated research activities.I wish you every success.

Respectfully,

PMD:srr (1211100)

6Medicol ScllrulUidminjs.lmtlon

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FFBIOGRAPHICAL SKETCH

Provide the follolHing information for the key personnel In the order listed on form Page 2.Photocopy this page or follow this format for each person.NAME POSITION TITLETom C.T. Yin Professor of Physiology

E D U C A T I O N I T R A I N 1 N G _ { B ~ g j n with baccalaureate or other /nft/al professionaleducation, such 8S nUTs/no, and Include sfdoctors/lra(nln .INSTITUTION AND LOCATION DEGREE YEAR(s) FIELD OF STUDY(i f aDDlie.ble)

Princeton University B.S.E. 1966 Electrical EngineeringUniversity ofMichigan Ph.D. 1973 Elect. & Compo Engin.Slate University ofNew York a t Buffalo Post-doc 1974 Biophysics & physiologyJohns Hopkins University Post-doc 1974-77 Physiology

RESEARCH AND PROFESSIONAL EXPERIENCE: Concluding wilh present poslilon. list, In chronological order, previous employment, experlence,and honors. Include present membership on any Federal Government public advisory commlUee. List, in chronological order. the titles, all authors, andcomplete references to all publications during the past three years and to represenlaUve earlier publlcatlons pertinent to this application. If the list ofpubllcallons In the last three years exceeds two pages, sel_ctthe most pertinent publlcallons. DO NOT EXCeED TWO PAGES.I 997-present1977-199719911984-19881992-1996

Professor of Physiology (by merger), Univ. of Wisconsin, Madison.Assistant professor to Professor, Dept. ofNeurophysiology, Univ. ofWisconsin, Madison.Visiting faculty, Vision, Touch and Hearing Research Centre, Univ. ofQueensland, Australia.Member ofN.I,H. Biopsychology Study SectionMember ofN.I.H. Hearing Research Study SectionResearch ongoing or completed during the last three years:NIH - NIDCD "Behavioral and physiological studies of sound localization" (T.C.T. Yin, P.I.)Type: ROI (DC02849, years 1-5) Period: March 1,1996 to February 28,2001.The overall goal of this project is to integrate behavioral and neurophysiological methods to study sound localization incats. The present application is the competitive renewal of this grant.

NIH - NIDCD Program Project "Research program on the neural basis of hearing," (J.F. Brugge, P.L). Project III on"Brainstem mechanisms of spatial hearing," (T.C.T. Yin, P.L)Type: POI (DCOOI16, years 23-28) Period: March I, 1999 to February 29, 2004.The objective of this project is to study the neural mechanisms of binaural hearing in the auditory brainstem, particularlyas they related to spatial hearing. We have studied the physiology and anatomy of cells in the central nucleus of theinferior eollieulus, superior olivary complex, and their afferents. The specific aims of the grant include the following:studies of the precedence effect in awake behaving cats, studies of the dorsal nucleus of the lateral lemniscus and itseffect on the inferior collicDlus, studies of the coding of localization cues using the virtual space technique in the lateralsuperior olive.NIH - NlDCD "Characterization ofmedial superior olivary circuits" (P.H, Smith, P.L)Type: ROI (DC01999, years 1-5) Period: July I, 1993 to June 30,1998The objective of this grant was to study the anatomical and physiological features of the afferents to the medial superiorolive as well as its projections to the inferior colliculus. Intracellular recordings both in vivo and in vitro were made fromMSa cells and their afferents followed by intracellular single cell labeling to allow us to characterize the anatomicalfeatures oflhe cell, using both light and electron microscopy.

Selected Relevant PublicationsLYNCH, J.C., MOUNTCASTLE, V.B., TALBOT, W.H., AND YIN, T.C.T. Parietal lobe mechanisms for directed visualattention. J. Ne/lrophysio/, 40: 362-389, 1977.

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Sciellce 197: 1381-1383, 1977.KUWADA, S., YIN, T.C.T., AND WICKESBERG, R.E. Rcsponse of cat inferior colliculus neurons to binaural beat stimuli:possible mechanisms for sound localization. Sciellce 206: 586-588, 1979.KUWADA, S. AND YIN, T.C.T. Binaural interaction in low-frequency neurons in inferior colliculus of the cat. I. E1Yeets

of long interaural delays, intensity, and repetition rate on interaural delay function. J. Neuropllysiol. 50: 981-999,1983.YIN, T.C.T. AND K[;WADA, S. Binaural interaction in low-frequency neurons in inferior colliculus ofthc cat. n. Effectsof changing rate and direction of interaural phase. J. Neuropllysiol. 50: 1000-1019, 1983.

Yin, T.C.T. and Kuwada, S. Binaural interaction in low-frequency neurons in inferior colliculus of the cat. 111. Effects ofchanging frequency. J. Neuropllysiol. 50: 1020-1042, 1983.KUWADA, S., YIN, T.C.T., SYKA, J., BUUNEN, T.J.F., AND WICK8SBERG, R.E. Binaural interaction in low-frequencyneurons in inferior colliculus of the cat. IV. Comparison of monaural and binaural response areas. J. Nellropllys;ol.

51: 1306-1325, 1984.HIRSCH, lA., CHAN, J.C.K., AND YIN, T.C.T. Responses of neurons in the cat's superior colliculus to acoustic stimuli. I.Monaural and binaural response properties. J. Neuropllysiol. 53: 726-745, 1985.YIN, T.C.T HIRSCH. J.A., AND CHAN, J.C.K. Responses of neurons in the cat's superior colliculus to acoustic stimuli. 11.A model of inter aural intensity sensitivity. J. Nellropllys;of. 53: 746-758,1985. .YIN, T.C.T CHAN, J.C.K., AND IRVINE, D.R.F. Effects of interaural time delays of noise stimuli on low-frequency cells

in the eat's inferior colliculus. I. Responses to wide-band noise. J. Nellropflysiof. 55: 280-300, 1986.CHAN, J.C.K., YIN, T.C.T., AND MUSICANT, A.D. Effects of interaural time delays of noise stimuli on low-frequencycells in the eat's inferior colliculus. II. Responses to band-pass noise. J. Neuropflysiol. 58: 543-561, 1987.YIN, T.C.T CHAN, J.C.K. AND CARNEY. L.H. Effects of inter aural time delays of noise stimuli on low-frequency cclls inthe cat's inferior colliculus. III. Evidence for cross-correlation. J. Neuropllysiol. 58: 562-583, 1987.CARNEY. L.H. AND YIN, T.C.T. Temporal coding of resonances by low-frequency auditory nerve fibers: single fiberresponses and a population model. J. Neuropllysiol. 60: 1653-1677, 1988.CARNEY, L.H. AND YIN, T.C.T. Responses of low-frequency cells in the inferior colliculus to interaural time differences

of clicks: excitatory and inhibitory components. J. Nellropllysiol. 62: 141-161, 1989.YIN, T.C.T. AND CHAN, J.C.K. Interaural time sensitivity in medial superior olive of cat. J. Nellropllysiof. 64: 465-488,

1990.OLIVER, D.L KUWADA, S., YIN, T.C.T., HABERLY, L.B., AND HENKEL, C.K. Dendritic and axonal morphology ofsingle neurons in the inferior colliculus of the cat. J. Comp. Neurol. 303: 75-100, 1991.SMITH, P.H., JORIS, p.x., CARNEY, L.H. AND YIN, T.C.T. Projections of physiologically-characterized globular bushy

cell axons from the cochlear nucleus of the cat. J. Comp. Neurol. 304: 387-407, 1991.JORIS, J.X., SMITH, P.H. AND YIN, T.C.T. Mechanisms of azimuthal sound localization in the central nervous system ofthe cat. J. Dutch Aeo" . . Soc. J04: 23-35. 1991.lORIS. P.X. AND YIN, T.e.T. Responses to amplitude-modulated tones in the auditory nerve of the cat. J. Aeoust. S/lc.Amer. 91: 215-232.1992.

YIN. T.C.T. AND GREENWOOD, M. Visual response properties of neurons in the middle and lateral suprasylvian corticesofthc behaving cat. Exp. Brain Res. 88: 1-14, 1992.

YIN, T.C.T. AND GREENWOOD, M. Visuomotor interactions in the middle and lateral suprasYlvian cortices of thebehaving cat. Exp. Brain Res. 88: 15-32, 1992.SMITH, P.H., JORIS, p.x., AND YIN, T.C.T. Projections of physiologically characterized spherical bushy cell axons frol11

the cochlear nucleus of the cat: evidence for delay lines to the medial superior olive. J. Comp. Neurol. 331: 245-260.1993.

JORIS, P.x.. CARNEY, L.H., SMITH, P.H. AND YIN, T.C.T. Enhancement of neural synchronization in the anteroventralcochlear nucleus. I. Responses to tones at the characteristic frequency. J. Nellropllysiol. 71: \022-1036, 1994.JORIS, p.x., SMITH, P.H AND YIN, T.C.T. Enhancement of neural synchronization in the anteroventral cochlear nucleus.

II. Responses to tones in the tuning curve tail. J. Nellropflyslol. 71: 1037-1051, 1994.YIN, T.C.T. Physiological correlates of the precedence effect and summing localization in the inferior colliculus of thecat. J. Nuurosci. 14: 5170-5186,1994.JORIS, P.X. AND YIN, T.C.T. Envelope coding in the lateral superior olive. I. Sensitivity to interaural time differcnces.

J. Nemopllysiol. 73: 1043-1062, 1995.PHS 398 (Rev. 4/98) (Form Page 6) Page _8_Number pages-consecutively at the bottom thrQughout the application. Do 001 use suffixes such as 3a, $b, FF

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FF DirectorrOPULlN, AND motoneuron pools that innervate the muscles of thc

pinna of the cat. J, Comp. Neurol. 363: 600-614, 1995.KUWADA, S., BATRA, R., YIN, T.C.T., OLIVER, D.L., HABBRLY, L.B., AND STANFORD, T.R. Intracellular recordings in

response to monaural and binaural stimulation of neurons in the inferior colliculus of the cat. J. Neurosci. 17: 7565-7581, 1997.lORIS, P.X. AND YIN, TOM C.T. Envelope coding in the lateral superior olive. Ill. Comparison with afferent pathways.J. Neurophysiol. 79: 253-269, 1998POPUL/N, L.C. AND YIN, T.C.T. Behavioral studies of sound localization in the behaving cat. J. Neurosci. 18: 2147-2160,1998.POPULlN, L.c. AND YIN, T.C.T. Pinna movements of the cat during sound localization. J. Neurosci. 18: 4233-4243.1998.SMITH, P.H., lORIS, P.X. AND YIN, T.C.T. Anatomy and physiology of principal cells of the cat medial nucleus of the

trapezoid body (MNTB). J. Neurophysiol. 79: 3127-3142, 1998.LiTOVSKY, R.Y., RAKERD, B., YIN, T.C.T. AND HARTMANN, W.M. Psychophysical and physiological evidence for a

precedence effect in the median sagittal plane. J. Neurophysiol. 77: 2223-2226, 1997.LiTOVSKY, R.Y. AND YIN, T.C.T. Physiological studies of the precedence effect in the inferior colliculus of the cat: I.

Correlates of psychophysics. J. Neurophysiol. 80: 1285-1301, 1998.LiTOVSKY, R.Y. AND YIN, T.C.T. Physiological studies ofthe precedence effect in the inferior colliculus of the cat: II

. Neural mechanisms. J. Neurophysiol. 80: 1302-1316, 1998.JORIS, PoX., SMITH, P.H. AND YIN, T.C.T. Coincidence detection in the auditory system: 50 years after Jeffress. Neuroll21: 1235-1238, 1998.DELGlJTrs. B., JORIS, PoX., LITOVSKY, RY. AND YIN, T.C.T. Responses to virtual-space stimuli in the cat inferior

colliculus. J. Types of sensitivity and binaural interactions J. Nellrophysiol. 81: 2833-2851,1999.POPULlN, L.C. AND YIN, T.C.T. Kinematics of eye movements of cats to broadband acoustic targets. J. Nellrophysiol.82: 955-962, 1999.

Book ChaptersYIN, T.C.T. AND KUWADA, S. Neuronal mechanisms of binaural interaction. In DYllamic Aspects of NeocorticalFUIICtioll. G.M. Edelman, W.E. Gall, and W.M. Cowan, Eds. New York: John Wiley and The NeurosciencesInstitute, pp. 263-313, 1984.KUWADA, S. AND YIN, T.C.T. Physiological mechanisms of directional hearing. In Directiollal Hearillg. W.A. Yost

and G. Gourevitch, Eds. Berlin: Springer Verlag, pp. 146-176, 1987.YIN, T.C.T. AND MEDJBEUR, S. Cortical association areas and visual attention. In Comparative Primate Biology, Vol. 4:Neurosciell,es. H.D. Steklis and J. Erwin, Eds. New York: Alan R. Liss, Inc., pp. 393-420,1987.YIN, T.C.T. AND CHAN, J.C.K. Neural mechanisms underlying interaural time sensitivity to tones and noise. In A u d i t o ' ~ 1

Fwwlion: Tile Neurobiological Bases o fHearing. G.M. Edelman, W.E. Gall, and W.M. Cowan, Eds. New York:John Wiley and The Neurosciences Institute, pp. 385-430, 1988.YIN, T.C.T. Audition. In Neurosciellce ill Medlcille P. Michael Conn, Ed. Philadelphia: J.B. Lippincott Co., pp. 485-499, 1994.YIN. T.C.T. AND SMITH, P.H. Electrophysiology of the central auditory system. Halldhook ofAcoustics. M.J. Crocker,

Ed. New York: John Wiley and Sons, Inc., pp. 1389-1400, 1997.YIN, T.C:r., lORIS, P.X., SMITH, P.R. AND CHAN, J.C.K. Neuronal processing for coding interaural time disparities. InBillaural alld Spatial Hearillg. R. Gilkey and T. Anderson, Eds. New York: Erlbaum Press, pp. 427-445, 1997.

YIN, T.C.T. AND POPlJLlN, L.C. Sound localization and pinna movements in the behaving cat. In Acoultical SigllalProcessillg ill the Central Auditory System. J. Syka, Ed. New York: Plenum Press, pp.399-405, 1997.YIN, T.C.T. AND POPULlN, L.C. Behavioral and physiological studies of sound localization. In Celltral Auditory

Processlllg alld Neural Modeling. J.Brugge and P. Poon, Eds., New York: Plenum Press, pp. 117-127, 1998.POPULlN, L.C. AND YIN, T.C.T. Sensitivity of auditory cells in the superior colliculus to eye position in the behaving cat.In Psychophysical alld Physiological Advallces ill Hearillg. A.R. Palmer, A. Rees, A.Q. Summerfield, and R.Meddis, Eds. London: Whurr Publishers, pp. 441-448,1998.

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ecipallnVeStigalOr/ProgramDirector (LBst, first, m l d d l . _ J ( J ! h . I Q ! ! ! . ~ ' I ' ___ .__ .__" __RESOURCES

FACILITIES: Spectfy the faellities to be used for the conduct of the proposed research. Indicate the performance sites and describe capacities,pertinenl capabilHles, relative proximity, and extenl of avallebllity 10 Ihe proJect. Under 'Olher," Idenllfy support . . vlees such as machine shop,electronics shop, and specify the extenllo which they will be available 10 the project. USB conilnuation page. n ecessary.Laboratory: Three laboratories{ ': }re available for this project. Please see detaileddescription below,

Clinical: N/A

Animal: [ The animals are housed in the animal care fac i l i t0--------- . - . ._ . t T r ; ; l s : - ; r u : ; ; ; ; n - ; ; ; y ; " : e ; ; ; x ; ; ; p " e " r " ' l e " n ; ' ; ; c : O e ; n ; s r . T " " u n - e < ; r ' " " " " e - ~ -supervIsion 0 a ve ennanan. e aCI Ity IS new y remodeled and accredited by the AmericanAssociation for the Accreditation of Laboratory Animal Care,computer. . 'Please refer to detailed description below.

Office: 75 sq, ft for P.I. and a 115 sq, ft, office the graduate assistant shares with another student,

Other: See attached,

-.... - ---------.-----:--:---:-- - - - - --::--c---: - - - _ . _ - - - - ...- - - - .. ..MAJOR EQUIPMENT: LIst the mostlmportanl equipment "ems already avaiable forthls project, nollng the _t ion and pertinant capabilHJes of each.See attached.

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___________________-::c--",-_=_=_=_=_===_=::,:rin::,:cI::pa:::1 m:::,:;_;;;.=o-=_ _ ",C=:;;,T ~ , =======C------- e vloral sound-Iocaltzatlon a oratory contains a single-wainsulated booth (7 x t e insIdes of which have been lined with 4" Sonex foam. A 3 foot magnetic searchcoil system (CNC Engineering) with three sets of phase detectors provide the ability to monitor the orientationsof three independent search coils (e.g. one each for eye. head and pinna movement). The present system iscontrolled by a microVAX II computer and the usual array of electrophysiological recording equipment (BAKpreamp. window discriminator. and audio monitor). two Tektronix storage oscilloscopes for monitoring X- Yeye position and neural activity. and an H-P tape recorder. Two locally-designed and build Digital StimulusSystems provide the acoustic waveforms. The DSS is a complete stimulus delivery system that includes timingcontrol. a present stimulus counter. an envelope multiplier. the ability to adjust signal amplitude automaticallyto maintain constant sound pressure level (for FM work). a digital-to-analog converter. and an attenuator with arange of 127 dB. Each DSS can synthesize sine waves with amplitUde or frequency modulation. Specialwaveforms (e,g. noise. speech. etc) stored in a dynamic RAM memory (2 MB. general waveform buffer) canbe generated by repeatedly cycling through that portion of RAM. A 16 channel. relay speaker selector connectseither DSS to any speaker as well as for control of the intensity of 16 LEDs for the visual stimuli. Thechamber is not very sound proof since many units can be driven by sounds made in the lab even when the dooris closed, We propose to replace this very old single-walled chamber with a new double-walled room with anew 5 foot search coil and new phase angle detectors and drivers so that large angle measurements ofeye/headlear position can be made.I *' laboratory is used by the P,Ls lab group for electrophysiological recordings using dichoticstllnulatlon. It tncludes an LA.C, double-walled sound-insulated chamber used for dichoticeleclrophysiological recording experiments, The lab is armed with a broad array of specialized peripheraldevices for delivering digital auditory signals. including a two-channel DSS, [n addition the lab has all of theelectrophysiological amplifiers. oscilloscopes. B & K microphones. earphones. microscopes. electrodepullers. etc, to carry out the proposed work, This includes Dagan 2400 extracellular and Dagan 8100intracellular amplifiers. Tektronix 2430 and 2220 digital storage oscilloscopes. and a locally built peak detectorfor timing spikes to the peak of the action potential. This facility can handle all of the acoustic calibrations.generation of stimuli. and data collection. storage. and analysis. to complete a wide range of single-neuronstudies,I X )aboratory was used by the P,Ls group for electrophysiological experiments using free fieldstimullitlOn. It contains a smaller (7' x 8') LAC, sound-insulated booth. the inside walls of which have beenlined with 4" Sonex foam to form an anechoic chamber, A semicircle of 13 matched speakers (Radio Shackmidrange tweeters) spaced at I 5-degree increments are mounted along the horizontal meridian at 95 cm radius,The speakers are selected by a 16 channel. relay speaker selector that uses input from a 8-bit parallel I/O, Twoindependent Crown amplifiers will drive the two speakers. This system is presently connected to a pair ofDSSs and a VAX station shared with another lab, A full complement of e1ectrophysiological recordingequipment (BAK pre-amps. AC amplifiers. window discriminator. oscilloscopes. and audio monitors) andTrent-Wells stepping motor microdrive are available for free-field physiological work. We are proposing touse this smaller sound-proof room for training of animals by moving the present search coil system into thisroom,Support Facilities at the Medical Science Center Instrumentation: The Medical Electronics Laboratory (MEL) isa well-equipped facility occupying some 900 sp, ft. of space adjacent to the Auditory Neurophysiology Labs,This facility. which serves the entire Medical School. has a full complement of testing and measurementequipment. Schematic design and layout of customized electronic equipment is greatly facilitated by CADsoftware (Or-CAD. Tango. EasyCAD) running on a PC/386, The shop is equipped with machine tools forfabrication. including benders, drill press. milling machine and lathe. The staff includes three full timeengineers or electronic specialists, Equipment fabrication is often done by student workers (engineeringundergrads), which keeps costs to a minimum, Mr, Daniel Yee (MEL Director) has been serving theDepartment for over 20 years and knows well the lab instruments and instrumentation needs of the PI.

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._-----_._----- ._____~ ~ ~ r i ~ n ~ ~ p ~ a l ~ l n ~ v ~ e s ~ t ~ ~ a ~ I O ~ d P ~ r ~ ~ r . ~ m ~ o ~ ~ e d ~ O ~ r ( ~ L . ~ S ~ ( ~ m ~ S ( ~ m ~ I A I t ~ ~ . ~ Y ~ i = n ~ , T ~ o ~ m ~ c ~ . T ~ . = = = = = = = = = = = = = = = Computing: The MSC laboratories, which are within the Department of Physiology, are linked via an ethemetbackbone to the campuswide fiber optic network described below. The network protocols include TCPIIP,NetBEUI, DECnet and AppleTalk. These computers are connected to network hubs via IOBaseT ethemetcables and the hubs are connected to a Cisco high speed switch via 100 Mbps fiberoptic cables. The MedicalSchool provides funds for connecting all computers and workstations to the main hub, as well as the rest of thecampus. The VAXstations all use the VMS operating system and X-windows, and are tied together via a LocalArea Cluster (LAVe), which means that devices such as disks, tapes and printers (and therefore databases andprograms) are shared transparently between alI workstations. Mr. Ravi Kochhar is responsible for monitoring,upgrading and maintaining the network.Campus-wide computing network: The University of Wisconsin-Madison places a major emphasis on the useof computer networks for both education and research. The Division of Infomlation Technology providescoordination as well as funds for the shared portions of this campus-wide resource. The campus-widenetwork (WiscNet), consists of a dual fiber optic backbone that connects all major buildings on the campus,including the MSC and WCMR. Both FDDI (100 Mbps) and oc3 ATM (155 Mbps) protocols are supportedon this back-bone. The campus network is also connected to the worldwide INTERNET through connectionsto NapNet. The University of Wisconsin is also a participant in the vBNS (very high-speed BackboneNetwork Service) project funded by NSF and MCI to connect major universities and labs via a 45 Mbpsnctwork.Neurohistology: Neurohistological service is provided by the histology laboratory of the Department ofPhysiology. This lab is fully equipped to carry out a wide variety of procedures, from standard Nisslpreparations to more demandin immunocytochemistry. It has a highly-experienced full-time neurohistologicaltechnician who prepare tissue for light- and electron-microscopic study. She is up-to- .date with a mo em neuroanatomical techniques, and has made important contributions to various researchprojects in our Department for many years. Related to the Neurohistology Lab is a Eutectics neuroanatomicalReconstruction System, located near the auditory rescarch labs.Auditory group at the University of Wisconsin: Research in the auditory system at many levels has had a longand distinguished history in the Department of Neurophysiology, which merged with the Department ofPhysiology in 1998. It began over 30 years ago under the direction of Drs. Jcrzy E. Rose and Clinton E.Woolsey and has continued and expanded considerably over the last 10-20 years. The primary mode ofinteraction within this group is a year-round seminar series which the P.I. established 15 years ago andcontinues in the form of a "Hearing and Donuts" meeting every Friday morning. Its major aim is to providecritique of work in progress and feedback to investigators early in the development of an idca or project. Allinvestigators, including those within the department and elsewhere on campus, with interest in the auditorysystem attend regularly. Talks are scheduled in tum and attendance is about 2 and a half dozen donuts worthso that a talk is given about every 9 months. A considerable number of talks are also given by visitingspeakers; over the last 5 years 35 s c i e n t i s t ~ from 28 institutions in 8 countries have pres . TheGlIow.i It . . ost-d" 'n his series: Dr

ere are ew ot erp aces In the wor w ere suc a arge an Iverse commUnIyo. ars assemble on a weekly basisto discuss issues of common interest, which include ion channel biophysics, hair cell transduction, coding inthe central auditory system, modeling of the auditory periphery and CNS, and human psychophysics. Thus,Hearing and Donuts provides several crucial services; a forum for everyone involved in auditory research tobecome familiar with work done in each lab, an avenue for students to present seminars on a regular basisbefore a friendly but critical audience, and an opportunity for outside speakers to address an unusually largeand active auditory community. This rich environment of interest in the auditory system provides an invaluableresource for this grant.In addition, the P.I. has close ties with other neuroscientists at UW-Madison who provide a rich andstimulating environment. In particul the resear interests of Drl ;g ,lwho presently teaches agraduate course with the P.I., and Dr Ith whom tlie P.I. taught medical students for 20 years,on the visual system and the superior co ICU us ovetail nicely with our interests.* _ ' I \ ~ u ~ \ o \ p o \ " 6 \.D+4i ~ 1 > \ D ~ ~ r l o

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rincipallnvesligalor: Yin. Tom C. T.A. SPECIFIC AIMSThe overall objective of this application is to combine behavioral and physiological studies of soundlocalization in the cat. We propose to extend our on-going behavioral studies of sound localization by moving to apreparation where the cat is free to move its head. This head-free preparation has significant advantages over our

present setup: it is a much more natural behavioral response that will allow us to explore a wider area of acousticspace. Our physiological studies will continue to study the motor error hypothesis in the superior colliculus aswell as to encompass studies of the auditory cortex in awake, behaving cats.Spccific Aim I will primarily be aimed at expanding our psychophysical studies of sound localization in thecat to the use of a head-free preparation. Specific aim la is directed toward developing the head-free preparationusing a variation of the standard operant conditioning paradigm that was developed successfully during theprevious grant period. Specific aim Ib will compare the accuracy of sound localization in the head-free and headfixed cat under similar conditions. We expect that localization will be more accurate in the more natural head-freecondition. Specific aim Ic will examine the effect of spectral cues provided by the filtering properties of thepinnae by testing the ability of the cat to localize narrowband noise bursts and artificial notched-noise stimuli. Weexpect that the cat will mislocalize the narrowband and notched-noise stimuli in a manner predictable from its headrelated transfer functions (HRTFs), which we will measure for each cat. Specific aim Id will examine the role of

pinna movements in sound localization in the cat using two approaches: one, using our traditional head-fixedpreparation in which pinna movements can be easily monitored we will study the effect of denervation of he pinnaon sound localization and two, we will measure pinna movements in the head-free cat using the delayed saccadetask where the head and eye movements can be delayed with respect to the onset of the sound.Specific Aim II will use the behavioral preparation for physiological studies of sound localization. SpecifIcaim lI a will continue our ongoing studies of the motor error hypothesis in the superior colliculus. Our preliminaryresults suggest that the presence of the modulation of auditory responses by eye position is dependent upon theextent of behavioral training of the animal, in particular on the ability of the cat to execute delayed auditorysaccades. Specific aim lI b will test the hypothesis that the activity of neurons in the central auditory system to anacoustic stimulus can be correlated with the cat's localization behavior. We propose to move to the primaryauditory cortex (AI) where we expect to find cells whose discharge properties are correlated with the eat'sperceived localization of the stimulus. One way we will influence the localizability of the stimulus is by varying

the bandwidth of he noise, a manipulation that is known to degrade localization that will be studied in specific ailllIc. By progressively narrow b8!1dpass filtering the noise stimulus, we expect the cat to gradually mislocalize thesound. If the cell is involved in the perception of the location of that sound, then we expect some aspect of itsresponse to correlate with the behavior. In addition, at some bandwidth the cat will be near 'threshold', lookinghalf the time at the proper location and the other half to some phantom location. At this point we have the uniquesituation whereby an identical stimulus results in two different behaviors, and we are then in a position to correlatethe neural activity to one behavior or another.B. BACKGROUND AND SIGNIFICANCE

IntroductionThe ability to localize the source of a sound is an important function of the auditory system. It is of obviousvalue for both prey and predator to quickly and accurately identify the location of a sound source. Consequently, themechanisms underlying sound localization have been of great interest to psychophysicists, anatomists andphysiologists studying the auditory system. Our lab has been studying the physiological and anatomical mechanismsby which sound localization cues are encoded in the central auditory system for the last 22 years. It is probably safe tosay that we understand more about the central processing of sound localization cues than that of any other auditoryattribute (e.g. pitch or loudness)(see Irvine '86, '92; Yin et aJ. '95).

The overall goal of this research program is to combine behavioral and physiological methods to study soundlocalization in cats. The ultimate goal is to record the activity of neurons in the auditory system that arc importantfor sound localization while the cat is actively engaged in a localization task. We believe that carefulpsychophysical study is a key ingredient to success in such a combined project. In the previous grant period wePage 17

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rincipal Investigator: Yin, Tom C. T.have demonstrated that we can train cats with their heads fixed to look at sound sources, study the psychophysicsof their behavior quantitatively, and record from cells in the brainstem while they are engaged in this task. In thepresent renewal we propose to extend the behavioral preparation to a more natural one in which the cat iscompletely free to move its head,ears and eyes, and we hypothesize that there will be correlations between theresponse properties of cells in the auditory cortex and cat's perceived localization of the stimulus,

We believe that this area of study consti tutes a significant vacuum in the auditory literature. Indeed it isremarkable how much attention is being paid to studies in awake, behaving animals in the visual andsomatosensory systems as compared to the auditory system. For example, in their review of the physiology ofperception, Parker and Newsome ('98) note that "remarkably, we have been unable to identifY studies of theauditory pathways in which neural signals have been measured at the same time as the subject is performing atnear-threshold levels in a detection or discrimination task. Although the activity of auditory nerve fibers hasreceived considerable experimental and theoretical attention, insight into the neural substrates of auditoryperception will ultimately require investigation of the central auditory pathways in the context of specificpsychophysical tasks."Psychophysics ofsound localization

The so-called classical "duplex theory" of sound localization, first clearly enunciated by Rayleigh (,07), hasprovided a convenient framework for much of the psychophysical and physiological investigations in this area. Thetheory proposes that localization of high frequency tones uses interaurallevel differences (!LDs) while localization oflow frequency tones depends upon detecting interaural time differences (ITDs). In mammals there appears to be ananatomical correlate of the duplex theory where !LOs and ITOs are processed in parallel in the superior olivarycomplex (SOC): cells in the medial superior olive are biased to low frequencies and tend to be sensitive to ITOs whilethose in the lateral superior olive are predominantly high frequency and ILO sensitive (Irvine '86, '92; Yin et aI., '95).Recently, attention has been directed toward another important localization cue, which we will refer to as"spectral" (Wightman and Kistler '94). By this we mean the changes in the spectrum of a sound source that areinduced by the presence of the torso, head and external ear. While the importance of the pinna and associated spectralcues has been debated for over a century (Pierce, '0 I), their role in sound localization was generally ignored untilBatteau ('66), who attributed it primarily to reflections from various parts of the pinna. We now think of these cuesnot in terms of reflections but rather the changes in spectra that result from the sum of these reflections (Shaw, '74).

The importance of pinna filtering is well-documented for localization of sounds with no interaural disparities, such asthose presented monaurally or in the vertical median plane (Hebrank and Wright '74a, '74b; Butler '75; Gardner andGardner '73: Middlebrooks '92).Specific Aim I: Behavioral studies ofSOUlld locjlllzationAlthough much is known about the physiological and anatomical mechanisms of sound localization in cats, lessis known about its behavioral capabilities. Many studies have explored the effect of lesions of various brain regionson localization ability. Usually, the tasks have either required the cat to approach two or more speakers (Casseday andNeff '73; jenkins and Masterton '82; Jenkins and Merzenich '84; Heffner and Heffner '88) or have employedconditioned avoidance to measure minimum audible angle (MAA, Martin and Webster '87; Heffner and Heffner '88).Unfortunately, neither task measures absolute localization ability, but, at best, measures the detectability of a changein source position or, at worst, of a change in some acoustical cue that covaries with location.

In many ways the results of these behavioral studies in nonnal cats mirror those from human psychophysicalstudies. Localization is more accurate under binaural than monaural conditions (Jenkins and Masterton '82), withwide band noise bursts than with tones, especially in the vertical dimension (Casseday and Neff '73; Martin andWebster '87; Huang and May, '96a). Sound localization acuity, as measured by the horizontal MAA, is highest forstimuli near the median sagittal plane and decreases at increasing azimuthal angles (Heffner and Heffner, '88; Huangand May, '96b). With pure tones, localization varies with frequency with a marked deterioration in the mid-frequencyrange (4 kHz) where ITDs and !LOs are not effective cues {Casseday and Neff, '73).

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rincipal Investigator: Yin. Tom c.r.The effects of lesions at various points in the auditory system on sound localization performance demonstrate the

importance of binaural input and the SOC for localization. Lesions ofthe trapezoid body, which provides input to themajor nuclei of the SOC, have severe effects on localization ability whereas section of higher acoustic commissureshave little effecl (Moore et a!. '74; Jenkins and Masterton '82). Lesions above the level of the SOC, e.g. laterallemniscus or auditory cortex, result in localization deficits in the contralateral sound field (Jenkins and Masterton '82),an effect which has been termed the acoustic chiasm (Masterton and Imig '84). Monaural localization is markedlyworse than normal binaural localization even after an extensive period of retraining (Moore et a!. '74; Neff andCasseday '77; Jenkins and Masterton '82).

Our experimental procedure, in which cats will be trained to look at the locus of sound sources, allows a measureof the absolute localization error, which is most similar to the head-pointing task used by May and Huang ('96),Thompson and Masterton (,78) and Beitel and Kaas ('93) in cats and Makous and Middlebrooks ('90) in humans.There are similarities between the results we have found in head-fixed cats with those described above. May andHuang ('96) and Beitel and Kaas ('93) both found that head movements towards sound sources showed a markedundershoot, similar to what we observed with eye movements to sound sources.Coordillated {.ead alld eye movements to sound The study most comparable to ow' proposed head-free preparationis that of May and Huang ('96). However, there are marked differences in the two preparations, and we believe tbatour proposed work has important advantages over theirs. First, we monitor eye position as well as head position sothat if the cat looks at the target but does not point its nose at it, we will have a better monitor of localization. This isan important difference: OUr goal is to determine the eat's perception of sound location and we believe that gaze willprovide a much more precise estimate of that perception. Second, May and Huang ( '96) did not reinforce their cats foraccurate localization. but rather to detect the onset of an LED at the speaker. which could easily be done withperipheral visioll. Third, to monitor the cat's head position, they used an electromagnetic device with 10 Hz samplingrate while we sample the output of the search coils at 500 Hz. This has allowed us to accurately study the kinematicsof the eye movement (Populin and Yin, '99). Fourth, we are able to monitor movement and position of the pinnaewhich show large and consistent movements associated with both visual and acoustic targets (Populin and Yin, '98b).These provide the fITst quantitative data on pinna movements during active sound localization in any animal.

Our preliminary data in head-free cats (see Progress Report) show that these differences in the preparation maybe significant: 1) the final eye position appears to be as accurate for acoustic targets as for visual ones; 2) the headmovement often shows an undershoot to targets located at large (45) deviations, which means that the eye must bedeviated from central position; 3) the latencies to head and eye movements are much shorter 100 msec) than the 300msec reported in May and Huang (,96); and 4) in many cases the head movement has a shorter latency so that thevestibulo-ocular reflex produces a small eye movement in the opposite direction (holding gaze onto the position of thenow extinguished fixation LED) before the saccade toward the target.

Coordination of eye and head movements to visual targets in cats and monkeys has been studied by a numher oflabs (Guitton et al. 'S4; Blakemore and Donaghy 'SO; Bizzi et al. '7\; Morasso et al. '73). Since we routinely have thecat localizing both visual and acoustic targets, as well as bimodal targets, at the same locations, we will be able toassess the differences between saccades to targets of different modalities. Guitton et al.(,S4) also found that the headmovement had a shorter latency for most visual saccades, though Blakemore and Donaghy ('80) found otherwise.Role Ofspectral cues

The role of spectral cues in sound localization has become a popular subject for study in recent years inhumans with the development of techniques to simulate fnie field studies over headphones (Wightman and Kistler,'89a; 89b; Kulkarni and Colburn, '98). Currently, it is not known which specific features of the sound spectrareceived at the ears is used for localization. In cat, the relevant cues are known to occupy a region of the spectrabetween approximately 5-18 kHz (Musicant et aI., '90; Rice et al., '92; Xu and Middlebrooks, '00). One way tostudy the role of spectral cues has been to perturb the sound spectra in various ways and measure the resultinglocalization performance. This has been done by using spectrally impoverished (pure tones or narrow band noise)stimuli in human subjects (Roffler and Butler, '68; Humanski and Butler, '84; Middlebrooks, '92) as well as in

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rincipal Invesligalor: Yill. Tom C. T.cats (May and Huang, '96; Populin and Yin, '98a) or by physically distorting the pinnae by occluding or bypassingit with tubes (Burger, '58; Gardner and Gardner, '73; Fisher and Freedman, '68; Oldfield and Parker, '84). Bothprocedures reliahly degrades localization performance, especially in the median plane. Others have artificiallyintroduced features into the spectra, such as narrowband notches, and measured the resulting localization (Bloom,'77; Watkins, '78). In our previous work, we have shown that narrow band filtered noise is systematicallymislocalized (Populin and Yin, '98a), but we need to repeat those observations with the head-free cat where thcrange of movements is much wider. The cat does not look to random positions but seems to hear the narrowbandnoise from specific locations. We hope to use these data to discriminate amongst the several models of localization(Middlebrooks, '92; Xu et al., '99; MacPherson, '98). Furthermore, these data are important for our proposedstudies linking physiological responses in AI to spatial perception of the sound in specific aim lIb.Role ofpi/rna movementsIt is now well-established that the acoustic filtering properties of the pinna are important for localization in thevertical dimension and for monaural localization. The HRTFs in humans and cats both show deep spectral notchesand broader peaks whose location in frequency varies systematically with stimulus position. However, the cat andhuman pinnae differ in one important respect: the eat's pinnae are mobile. Movements of the pinnae change thedirectionality of the external ear (Calford and Pettigrew, '84; Middlebrooks and Knudsen, '87), the frequency of thenotches and peaks in the HRTFs (Young et al., '96), and the spatial properties of the =eptive fields of cells in thedeep layers of the superior colliculus (Middlebrooks and Knudsen '87).

The cat's pinna is innervated by a complex arrangement of 22 muscles, which can move the pinna in a number ofdirections as well as change its shape (Crouch, '69). The motoneurons that innervate the pinna are located in the facialnucleus and are arranged topographically according to the primary action of the muscle (populin and Yin '95). Thefacial nucleus receives input from the paralemniscal region of he lateral midbrain tegmentum (Henkel '81) which inturn receives input from the deep layers of the superior colliculus (Henkel and Edwards '78). Stimulation of the deepSC produces discrete pinna movements that are topographically arranged according to the locus of stimulation (Steinand Clamann '81).

There is surprisingly little information available on the extent to which animals with movable pinnae actuallyuse the mobility for accurate sound localization. H


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rincipal Investigator: Yin, Tom C. T.movements. Both Heffuer and Heffner ('88) and May and Huang ('96) found performances ofcats on a MAA and ahead orientation experiment, respectively, using both short (40 msec) and much longer duration stimuli weresimilar and concluded that movements of the pinnae had little effect. On the other hand, Jenkins and Masterton('82) found that monaural localization was improved by longer duration stimuli, which they attributed to scanningmovements of the head or ears. Our measurements show that the latencies to pinna movements can be as short as15 msec, though the mean was 35 msec(Populin and Yin, '98b). We propose to study the effects of pinna mobilityin two ways: I) by recording the movements of the pinnae during active sound localization using the delayedsaccade task where we can vary the duration of the stimulus and 2) by studying the effect ofdenervating the pinnaeon localization behavior.Specific Aim III Physiological studies ofsound localization in behaving animalsThe long term goal of this project is to do record from neurons thought to be involved in sound localizationin cats while they are actively engaged in a localization task. There are a number of important advantages of thispreparation. First, it eliminates the problems associated with anesthesia, which are especially strong in the CNSwhere barbiturates are known to potentiate inhibitory processes (Barker and Ransom '78; Kl1wada et al. '89).Second, it has been shown, mostly in the visual system, that the behavioral state of the animal can stronglymodulate the activity of single cells, even those early in sensory pathways (Wurtz and Mohler '76; Mountcastle etal. '81). Third, cells in the eNS can show both sensory and motor response components as well as an interactionbetween them, e.g., the sensory response of cells may be enhanced when the animal is about to make a saccade to alight target as compared to the response when the animal can ignore the light (Goldberg and Wurtz '72; Yin andMountcastle '77; Yin and Greenwood '92). Fourth, the behavioral and physiologicnl experiments are performed onthe same animal under identical experimental conditions. Fifth, a major limitation of physiological recordings inanesthetized animals is that it is not possible to make strong inferences about the exact role ofany cell in any givenbehavior. However, by recording in behaving animals, we can correlate the activity of individual cells or groups ofcells to the perception or behavior of the animal (Newsome et al '89). For example, if the activity of a cell isimportant for the perception of sound location, then its activity would be expected to be strongly correlated withthe cat'sperception of the sound source, regardless of the physical attributes of the acoustic stimulus. We will testthis hypothesis by having the cat work on a task in which it occasionally misperceives the location of the soundsource. The use of awake, behaving animals has been exploited very successfully in studies of the oculomotorsystem (Moschovakis and Highstein '94), visual (Andersen '87; Miyashita '93; Parker and Newsome, '98), andsomatosensory systems (Recanzone et aI., '92; Johnson and Hsiao, '92; Bushnell et aI., '93) which contrastssharply with the relative lack of progress using this preparation in studies of the auditory system with some notableexceptions (Benson et al. '81; May and Sachs '92).Modulatioll ofauditory receptiveJields by eye position III Ihe SCThe mammalian superior colliculus (SC) has been a model system for studying sensorimotor interactions.particularly for oculomotor responses. Visual input from retinal ganglion cells arrives to the superficial layers Whilethe deep layers receive visual, auditory and somatosensory input (Sparks '86). Recordings from awake animals haveshown a wide variety of oculomotor-related responses in both the monkey (Wurtz and Goldberg '72; Mays and Sparks'80) and the cat (Peck et al. '80; Munoz and Guitton '91'; Guitton and Munoz '91). There is a retinotopic map of thecontralateral visual field in the superficial and deep layers, and corresponding auditory and somatosensorytopographical maps in the intermediate and deep layers (Gordon '73; Stein et al. '76b; Palmer and King '82;Middlebrooks and Knudsen '84). Furthermore, the three maps seem to be in colTespondence with frontal spacerepresented rostrally in the SC and points progressively more contralateral represented more caudally. Stimulation ofthe deep SC produces eye, head and pinna movements (Robinson '72; Roucoux et al. '80; Stein and Clamann '81).

As first pointed out by Poppel (,73), since the coordinate system of the visual map is retinotopic and that of theauditory map is head-related, the visual and acoustic maps can only be in register when the animal is looking straightahead. The question arises, "What happens when the animal moves its eyes?" In the most complete and careful study,Jay and Sparks ('87b) showed that the auditory receptive fields of cells in the deep SC of monkeys shift with theposition of the eyes, which seemed to show that the cells are coding motor error. In the -cat Pecket al. ('95) andHartline ot al. ('95) also reported data in support of the motor error hypothesis, while Harris et al. ('80) found no shift

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rincipallnvest/gator: YIII. Tom C. T.in receptive fields of auditory cells in the cat with eye movements. However, the three studies in the cat are, in ourview, incomplete and not carefully done. In none of them are the cats trained extensively: Peck et al. ('95) onlyrequired the cats to move in the general direction of the acoustic targets and Harris et al. ('80) and Hartline et al. ('95)did virtually no training. As a result they have little control of eye position, the most relevant behavioral parameter,and none of these papers show superimposed traces of eye movements even when dot rasters are illustrated. Incontrast we have found that extensive and careful training (on the order of 4-6 months or more) is necessary to havegood control of eye position and to demonstrate the motor error effect. Furthermore, the illustrations of auditoryresponses in all three papers are unconvincing so it is difficult to interpret the effects of eye position.SOUlld localizatioll ill tile primary auditory cortexAmple evidence suggests that the primary auditory cortex (AI) plays an important role in soundlocalization. Lesions of AI result in deficits in localization of sound in the sound field contralateral to the lesion inhuman subjects (Sanchez-Longo and Forster, '5S; Klingon and Bontecou, '66) and cats (Whitfield et al., '72;Jenkins and Masterton, '82; Jenkins and Merzenich, 'S4). Physiological recordings show that neurons in Al arespatially selective (Middlebrooks and Pettigrew, 'SI; Imig et aI., '90; R!\ian et aI., '90a; '90b; Clarey et aI., '94;Brugge et aI., '94) although the receptive fields of Al cells are large and may expand with increasing sound levels.Most studies of AI have found cells with receptive fieldsof several different classes: most are tuned to a portion ofthe contralateral sound field, some fields are in the frontal region of space, and a minority are omnidirectional,prefer the ipsilateral field or have complex fields (Raj an et al. '9Sa;'9Sb; Bruggeet aI., '96). It has beenhypothesized at least since Eisenman ('74) that the temporal response pattern in addition to spike discharge ratemight encode information about sound location. More recently, this hypothesis hilS been tested by Jenison ('98),who examined the latency of responses of cells in AI, and Middlebrooks and his colleagues who demonstrated thatthe responses of cortical cells in the anterior ectosylvian sulcus and secondary auditory cortex (AIl) can encode thelocation of a sound source at any azimuthal angle with varying degrees ofaccuracy using a neural network decoder(Middlebrooks et al.. '98). Based on the evidence above, it seems reasonable to assume that the response of cells inthe auditory cortex are related to localization behavior. An advantage of auditory cortex over the superiorcollicuI us, which we are currently studying, is that almost any cell encountered in Al will be a viable candidate forstudy whereas that is not the case for cells in the deep and intermediate layers of the SC, where only a subset canbe driven by acoustic stimuli. All of the physiological studies cited above were done in anesthetized animals inwhich the response to a best frequency tone or noise burst may be a short onset response. Recordings from Al ofthe unanesthetized cat or monkey are rare (Merzenich and Brugge, '73; Vaadia et aI, '82; Schwartz and Tomlinson,'90). and even rarer are recordings made in animals that are actively attending to sound (Hocherman et al. '76;Benson and Hienz, '78; Benson et aI., 'SO).The physiology ofperceptioll The goal of this specific aim lIb is to link perception and the responses of singleneurons. Our strategy follows closely from that adopted by Newsome and his colleagues in studies of motionperception in the MT cortical area (Newsome et al., '89; Britten et aI., '92; Parker and Newsome, '98). In thosestudies monkeys were trained to indicate the direction of movement of a random dot display in which a fraction ofthe dots on each refresh were moving in one direction. By adjusting the degree of correlation of the movement(100% means all dots move in the same direction while 0% would be all dots moving randomly), one could makethe task trivially easy to impossible. Psychometric functions were found from the behavior of the monkey byplotting the percent of correct judgements against motion coherence. Cells in MT were then found and the stimuliwere optimized for the characteristics of the cell, i.e., the random dot display was set in the middle of the cell'sreceptive field and movement was set to the optimal directionality of the cell. Neurometric functions weregenerated by examining the responses of the neuron in terms of an ideal observer (Green and Swets, '66). Thepsychometric and neurometric functions were highly correlated for a population of over 200 cells in MT,suggesting that the activity of MT cells could account for the directional sensitivity of the monkey. Similarexperiments have been done in the somatosensory system (Bushnell et aI., '93; Sinclair and Burton, '91)

Additional evidence for believing that the MT response was related to behavior derives from examinationof the covariation of neural and behavioral responses on a trial-by-trial basis. By setting the motion coherence to beat threshold level on a small proportion of trials an ambiguous stimulus could be delivered forcing the monkey to

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rincipal Investigator: Yin. Tom C. T.choose the perceived direction. Even though the monkey's performance was at chance, Britten et al.(,92) foundthat the monkey's choices on individual trials tended to be correlated with the discharge rate of the neurons understudy. Using a signal-detection metric to compute the proportion of trials in which an ideal observer could predictthe behavior based upon the neuron's response, some neurons showed robust predictive powers of about 70%,though for the population the mean was a very modest 56%, where chance was 50%. Thus, some neuronscorrelated highly with the behavior on a trial-by-trial basis while others were only weakly related. Similarexperiments have been done in the somatosensory system (Vallbo and Johansson, '16; Dubner et aI., '89) but nonehave been reported in the auditory literature.

C. PRELIMINARY STUDIESIPROGRESSREPORTSpecific alms of the previous grant periodThere were five specific aims in the original grant application:I) to study the psychophysics of sound localization in the behaving cat,2) to compare orientation to virtual space with field stimuli to see if the cat localizes the virtual space stimuli

to the corresponding positions from which the HRTFs were measured,3) to determine whether cats exhibit summing localization and the precedence effect,4) to monitor movements of the pinna during active sound localization5) to study single unit responses from the superior and inferior colliculus of behaving cats.

Specific aim I: Sound localization in the behaving catThe primary goal of the previous grant period was to develop the behavioral sound localizationpreparation. This goal has been achieved (Populin and Yin, I 998a) and the preparation is now standard procedurein the lab. To summarize, using operanfconditioning techniques with food deprivation and reward, we trained catsto look at light and sound sources with their heads held stable. Eye movements were monitored with the scleralsearch coil technique by surgically implanting a coil of wire around the eyeball. Training consisted of a variety oftasks mostly involving initial fixation of a visual target followed by a saccadic eye movement to a visual and/oracoustic target. In some cases with the delayed saccade task there were two potential targets and the cat had to betrained which target to fixate. An electronic window was placed around the target, and the cat was required tomaintain eye position within the window during the specified time period. There was considerable variability in thetime required to train individual cats, rangingfrom several weeks to several months. Visual AuditoryEye movements to visual targets weremore accurate, more highly stereotyped, andmore consistent than those to long-duration

noise targets in the same spatial positions. Eyemovements in auditory trials generallyundershot their targets and displayed anunusual slow component at their outset(Populin and Yin, 1999) (Fig. I). On theother hand these data demonstrate that catswere able to look to the location of auditorytargets, albeit with less accuracy than to visualtargets. Localization accuracy of singleclicks was diminished compared with thelong-duration stimuli. Control experimentswith novel auditory targets, never associatedwith visual targets, demonstrated that the catslocalized the sound sources using acousticcues and not from memory.

To examine the role of spectral cues,

20'iii'g>11):E.1l o . .--j&I*!:10III 20500 o(msecs) Time ImSl,cslFig. 1 Eye movements (0 visual (left) and acoustic (rigllt) largels Oil/he vertical(top) and IlOr/zolllat (bottom) meridians. Traces are synchronized 10 'he ol/sel oJ/hetargel al 0 msee.

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e used narrow-bandpass noise stimuli delivered

from the same speaker positions used in the broadband localization experiments. If spectral cues areimportant. then narrow-band stimuli such as thesewith impoverished spectral infonnation would beexpected to have a greater detrimental effect onvertical localization. because stimuli presented fromtargets on the mid-sagittal plane contain minimalinteraural time or level disparities. The results fromthe localization of targets on the midsagittal planesupport the hypothesis that spectral cues areimportant (Fig. 2). Large localization errors of thevertical target at (0._14) were observed in all fivenarrow-band conditions. Localization of narrowband stimuli on the horizontal axis did not follow theexpected outcomc. however. From MAA studies. wehad anticipated that horizontal localization would benonnal at low and high frequencies. at which lIDsand ILDs would p r o \ ~ d e cues for azimuthallocalization. but disrupted for stimuli in the 2-4 kHzrange. Indeed, localization was near normal at thelowest frequency and progressively disrupted as thecenter frequency increased. but it did not recover atthe highest frequencies. Interestingly. thepercentage of no-response trials. which in thesecases were always seen as a lack of an overt eyemovement. was highest for the 4 kHz bandpass

..-...C )Q)"C-:olw

rincipallllvestigator: Yill, Tom C 7:.4 kHz

10

o, t O ~

Azimuth (deg)Fig. 2 Mean /ocalizQfioll errorsofhroadband al)d bandpass (116 octave)lIoise stimuli centered a/ 5 different frequencies. Open symbols indicatetarget locatlon,filled symbols are meanflllol eye position. Arrows indiculemean errors> 7 deg.

condition (1.0 kHz, 15%; 2.0 kHz. 26%; 4.0 kHz. 43%; 8.0 kHz, 30%; and 12.0 kHz. 25%).problem of inferring from MAA data something about localization accuracy. These data highlight the

For most of our b e h a ~ o r a l tasks the acceptance window was centered about the target. and a food rewardwas given to the cat when it satisfied the spatial and temporal requirements. However, in some of the experimentsin which the perceived location orthe sound was was expected to be mislocalized (e.g., the narrow band signals) orwas an illusion (e.g. the summing localization task, see below), it was unclear where the "correct" target lies. Inthese cases. we wished to avoid training the cat to respond in a certain way by rewarding it only for particularresponses. Therefore for these experiments we adopted a different strategy in which such trials were presented atlow probability (5-10%), randomly intermingled with other nonnal localization trials, and the cat was alwaysrewarded, regardless ofthe response.Specific aim II : virtual space stimulation in behaving catProgress on this aim has been stalled because of technical problems with getting cats to tolerate and to fitan ear insert.Specific aim ]11: behavioral test of summing localization and the precedence effectUsing the behavioral preparation, we tested whether cats experience the precedence effect and summinglocalization in a manner similar to that seen in human subjects. To detennine the position of a sound source inenclosed spaces in which there are echoes, the nervous system must somehow deal with multiple copies of theoriginal signal that result from reflections. The precedence effect (Wallach et aI., 1949; Haas, 1951) is thought tofacilitate localization in such reverberant environments (Hartmann, \983). We studied the precedence effect bypresenting pairs of clicks with an interclick delay (ICD) from speakers located symmetrically about the cat. [CDsof


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rinclpallnvesligalor: Yin, Tom C. T.the phantom source, but there are no comparable studies incats, though earlier psychophysical (Cranford, 1982) and Aphysiological (Yin, 1994) studies suggest that cats shouldexperience a similar effect.

Figure 3 shows eye movements of a cat who waspresented with stimuli mimicking the precedence effect during ithe course of localizing a variety of more normal stimuli. Since! ,U I ..1 , ".these summing localization stimuli represent an auditory & :gg: ~ : ~ : : : : illusion, we prcsented them at low probability in the midst of 311 'In910


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rincipal Investigator: Yin. Tom C. T.and (0,_14). For ICDs longer than 2 msec, the


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rincipalInvestigalor: Yin, Tom C. T.I. Prominent and consistent pinna movements accompany eye movements when the animal orients to eitherauditory or visual stimuli. (Fig. 5). In visual trials the pinna movements occur at about the same time as the eyemovements, suggesting that they are part of the general orientation response of the animal. In auditory trials thepinna response was composed of two movements: short- and long-latency components. Whereas the long-latencycomponent seemed to occur with the eye movement to the target, the short-latency component was coupled to theonset of the stimulus (-25 msec latency) and was highly asymmetrical, being largest in the pinna ipsilateral to thestimuli. The short latency component therefore was also present when the cat was not required to make an eyemovement but merely fixated a visual target (Fig. 6). Thus, the ipsilateral pinna oriented towards the direction ofan acoustic signal with a short latency response while the contralateral pinna was largely unresponsive.Specific aim V: single unit recordings from the superior and inferior coliicull In the bebaving cat.

For our initial electrophysiological studies in the behaving cat,we have recorded from visual and auditory cells in the deep andintermediate layers of the superior colliculus, The mammalian superiorcolliculus (SC) has been a model system for studying sensorimotorinteractions.

From results of microstimulation experiments, Guillon et al. ('80)suggested that there may be a differences in the organization of the SC ofthe cat and monkey since goal-oriented saccades were elicited in the caudalSC while vector saecades were produced rostrally (but see Stein et al. '76a),We have begun to re-examine this question by recording from the SC incats that are working il) our behavioral preparation. We hypothesize thatcells with auditory receptive fields that shift with eye position are in therostral SC where vector-saccades are elicited by microstimulation, whilecells in the caudal SC where goal-directed saccades are evoked do not shiftwith eye position. Our preparation has considerable advantages to the Pecket al. ('96) and Hartline et al. ('96) studies: our cats are well-trained so that

Fig. 7. A dorsal view of he teclum i/J cal06.11,. super/or (SC) and /njer/or eoJ/iel/li (10are readily visible. Ti,e cross-hatched regiollshows the area of pelletralio/ls made illtoboth sides.we have control over their eye position, we have studied a much larger L -_____________ - - 'sample of cells than either study, and we know roughly where the ears are.

Fig. 7 shows a photograph of a dorsalview of the tectum of cat06. The stipplingshows the areas of the SC penetrated by ourmicroelectrodes, The pin was inserted at thetime of perfusing the brain at a known site inthe recording chamber so that penetrationsmade through the chamber can be referencedto it.

Figure 8 shows the responses of a cellin the right SC to the identical acousticstimulus while t