methods results conclusions selective hippocampal cholinergic deafferentation disrupts exploratory...

1
Methods Results Conclusions Selective hippocampal cholinergic deafferentation disrupts exploratory trip organization D.G. Wallace*; S.K. Knapp; J.A. Silver; M.M. Martin; S.S. Winter Dept of Psychology, Northern Illinois Univ., DeKalb, IL, USA Long Evans female rats either received injections of 192 IgG-Saporin (MS SAP) or saline (SHAM) into the medial septum. Subsequent to recovery, rats were placed on a large circular table with access to a refuge under complete dark conditions (infrared cameras and goggles were used to visualize the rat). Rats were free to explore the table for 50 minutes. Exploratory sessions continued until rats made eight trips that were at least half-way across the table. Figure 1 : Topographic and kinematic characteristics are plotted for a single representative exploratory trip. The searching segment of the trip is a sequence of progressions. The homeward segment is a single progression after the last stop. Figure 4 : Topographic (top panels) and kinematic (bottom panels) characteristics are plotted for eight searching segments from representative SHAM (left hand panels) and MS SAP (right hand panels) rats. Figure 2 : Coronal hemi-sections stained for AchE are presented for representative SHAM and SAP rats. Average cortical and hippocampal optical densities are plotted for both groups. Medial septum lesions significantly reduced markers of cholinergic function selective to the hippocampus. Figure 5 : Max speed (A), path circuity (B), standard deviation of peak location (C), and stop duration (D) are plotted for each class of searching segment progressions. Groups did not differ in their searching segment characteristics. Figure 8 : Max speed (A), path circuity (B), standard deviation of peak location (C), and stop duration (D) are plotted for the homeward segments. MS SAP rats’ homeward segments were significantly more circuitous, were more variable in their peak speed location, and had larger errors in distance relative to SHAM rats. Figure 6 : Topographic characteristics of four trials from a representative SHAM (top panel) and MS SAP rat (bottom panel) are shown under uncued conditions. Figure 7 : Topographic (top panels) and kinematic (bottom panels) characteristics are plotted for eight homeward segments from representative SHAM (left hand panel) and MS SAP (right hand panel) rats. Figure 9 : Three different measures of searching segment organization were used to predict the distance error associated with the homeward segment: 1) correlation between all searching segment linear and angular speeds; 2) correlation between linear and angular speeds during periods of high angular speeds (>10 deg/sec); 3) correlation between linear and angular speeds during periods of high linear speeds (>.1m/s). Only linear-angular correlations during periods of high linear speed were predictive of homeward segment distance error. •Both groups established home bases in the refuge quadrant and organized their exploration around that location. •Selective hippocampal cholinergic deafferentation disrupted exploratory trip organization specific to the homeward segment. •Group differences in exploratory trip organization were observed in the absence of environmental cues. These disruptions may be related to an impaired processing of self- movement cues generated on the searching segment of the exploratory trip. •The novel finding that the searching segment linear-angular speed correlation (i.e., during periods of high linear speed) is predictive of distance error on the homeward segment provides further support for rats using self-movement cues to organize exploratory behavior. Correspondence: D. Wallace [email protected] Web: www.niu.edu/user/tj0dgw1 Support Contributed By: NINDS grant NS051218 743.17 Introduction Controversy surrounds the role of hippocampal cholinergic function in spatial orientation. Non-selective medial septum lesions have been shown to disrupt performance on a variety of spatial tasks; however, the results are less conclusive when lesions are selective for cholinergic cells in the medial septum. These observations have been taken as evidence against a role of the hippocampal cholinergic function in spatial orientation. The forgoing studies typically used spatial tasks in which rats had access to environmental and self- movement cues; therefore, spared performance associated with selective lesion techniques may have reflected compensatory mechanisms rather than intact spatial orientation. The current study examines the effects of selective hippocampal cholinergic deafferentation on self-movement cue processing associated with exploratory trip organization. Tim e (s) 0 20 40 60 80 100 120 140 Speed (m /s) 0.0 0.2 0.4 0.6 0.8 Tim e (s) 0 20 40 60 80 100 120 140 Speed (m /s) 0.0 0.2 0.4 0.6 0.8 Tim e (s) 0 1 2 3 4 5 6 7 8 9 Speed (M /S) 0.0 0.2 0.4 0.6 0.8 Tim e (s) 0 1 2 3 4 5 6 7 8 9 Speed (M /S) 0.0 0.2 0.4 0.6 0.8 Tim e (s) 0 10 20 30 40 50 60 70 80 Speed (m /s) 0.0 0.2 0.4 0.6 0.8 Figure 3 : Preference for the home base quadrant (left hand panel) and total travel distance (right hand panel) are plotted for both groups. Groups were equivalent in their preference for the home base quadrant and total distance traveled. Q uadrantpreference 0.0 0.2 0.4 0.6 0.8 1.0 SHAM M S SAP D istance (m ) 0 50 100 150 200 LastStop M ean Stops FirstStop C hange in H eading (D egrees) 0 20 40 60 80 100 120 140 160 SHAM M S SAP Path C ircuity 0.0 0.2 0.4 0.6 0.8 1.0 M ax Speed (m /s) 0.0 0.2 0.4 0.6 0.8 1.0 SHAM M S SAP Path C ircuity 0.0 0.2 0.4 0.6 0.8 1.0 Short Medium Long StD ev Peak Location 0.00 0.05 0.10 0.15 0.20 Short Medium Long Stop D uration (s) 0 2 4 6 8 10 M ax Speed (m /s) 0.0 0.2 0.4 0.6 0.8 1.0 SHAM M S SAP Path C ircuity 0.0 0.2 0.4 0.6 0.8 1.0 * StD ev Peak Location 0.00 0.05 0.10 0.15 0.20 * Errorin D istance Estim ation 0.00 0.05 0.10 0.15 0.20 * C ortex Hippocam pus O ptical D ensitiy 0 20 40 60 80 100 120 140 SHAM M S SAP * -1.0 -0.6 -0.2 2.0 H om ew ard Segm ent D istance Error 0.00 0.10 0.20 0.30 -1.0 -0.6 -0.2 2.0 0.00 0.10 0.20 0.30 -1.0 -0.6 -0.2 2.0 H om ew ard Segm ent D istance Error 0.00 0.10 0.20 0.30 -1.0 -0.6 -0.2 2.0 0.00 0.10 0.20 0.30 O utw ard Segm ent Linear-AngularC orrelation -1.0 -0.6 -0.2 2.0 H om ew ard Segm ent D istance Error 0.00 0.10 0.20 0.30 O utw ard Segm ent Linear-AngularC orrelation -1.0 -0.6 -0.2 2.0 0.00 0.10 0.20 0.30 A B C D A B C D SHAM MS SAP All All High Circuity High Circuity No Stops No Stops R=0.140 F(1,94)=1.89, p=ns R=0.024 F(1,94)=0.055, p=ns R=0.275 F(1,94)=7.667, p<.01 R=0.219 F(1,38)=1.912, p=ns R=0.148 F(1,38)=0.847, p=ns R=0.259 F(1,38)=2.724, p=ns

Post on 19-Dec-2015

215 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Methods Results Conclusions Selective hippocampal cholinergic deafferentation disrupts exploratory trip organization D.G. Wallace*; S.K. Knapp; J.A. Silver;

Methods

Results

Conclusions

Selective hippocampal cholinergic deafferentation disruptsexploratory trip organization

D.G. Wallace*; S.K. Knapp; J.A. Silver; M.M. Martin; S.S. Winter Dept of Psychology, Northern Illinois Univ., DeKalb, IL, USA

Long Evans female rats either received injections of 192 IgG-Saporin (MS SAP) or saline (SHAM) into the medial septum. Subsequent to recovery, rats were placed on a large circular table with access to a refuge under complete dark conditions (infrared cameras and goggles were used to visualize the rat). Rats were free to explore the table for 50 minutes. Exploratory sessions continued until rats made eight trips that were at least half-way across the table.

Figure 1: Topographic and kinematic characteristics are plotted for a single representative exploratory trip. The searching segment of the trip is a sequence of progressions. The homeward segment is a single progression after the last stop.

Figure 4: Topographic (top panels) and kinematic (bottom panels) characteristics are plotted for eight searching segments from representative SHAM (left hand panels) and MS SAP (right hand panels) rats.

Figure 2: Coronal hemi-sections stained for AchE are presented for representative SHAM and SAP rats. Average cortical and hippocampal optical densities are plotted for both groups. Medial septum lesions significantly reduced markers of cholinergic function selective to the hippocampus.

Figure 5: Max speed (A), path circuity (B), standard deviation of peak location (C), and stop duration (D) are plotted for each class of searching segment progressions. Groups did not differ in their searching segment characteristics.

Figure 8: Max speed (A), path circuity (B), standard deviation of peak location (C), and stop duration (D) are plotted for the homeward segments. MS SAP rats’ homeward segments were significantly more circuitous, were more variable in their peak speed location, and had larger errors in distance relative to SHAM rats.

Figure 6: Topographic characteristics of four trials from a representative SHAM (top panel) and MS SAP rat (bottom panel) are shown under uncued conditions.

Figure 7: Topographic (top panels) and kinematic (bottom panels) characteristics are plotted for eight homeward segments from representative SHAM (left hand panel) and MS SAP (right hand panel) rats.

Figure 9: Three different measures of searching segment organization were used to predict the distance error associated with the homeward segment: 1) correlation between all searching segment linear and angular speeds; 2) correlation between linear and angular speeds during periods of high angular speeds (>10 deg/sec); 3) correlation between linear and angular speeds during periods of high linear speeds (>.1m/s). Only linear-angular correlations during periods of high linear speed were predictive of homeward segment distance error.

•Both groups established home bases in the refuge quadrant and organized their exploration around that location.•Selective hippocampal cholinergic deafferentation disrupted exploratory trip organization specific to the homeward segment. •Group differences in exploratory trip organization were observed in the absence of environmental cues. These disruptions may be related to an impaired processing of self-movement cues generated on the searching segment of the exploratory trip. •The novel finding that the searching segment linear-angular speed correlation (i.e., during periods of high linear speed) is predictive of distance error on the homeward segment provides further support for rats using self-movement cues to organize exploratory behavior.

Correspondence:

D. Wallace [email protected]

Web: www.niu.edu/user/tj0dgw1

Support Contributed By: NINDS grant NS051218

743.17

IntroductionControversy surrounds the role of hippocampal cholinergic function in spatial orientation. Non-selective medial septum lesions have been shown to disrupt performance on a variety of spatial tasks; however, the results are less conclusive when lesions are selective for cholinergic cells in the medial septum. These observations have been taken as evidence against a role of the hippocampal cholinergic function in spatial orientation. The forgoing studies typically used spatial tasks in which rats had access to environmental and self-movement cues; therefore, spared performance associated with selective lesion techniques may have reflected compensatory mechanisms rather than intact spatial orientation. The current study examines the effects of selective hippocampal cholinergic deafferentation on self-movement cue processing associated with exploratory trip organization.

Time (s)

0 20 40 60 80 100 120 140

Sp

eed

(m/s

)

0.0

0.2

0.4

0.6

0.8

Time (s)

0 20 40 60 80 100 120 140

Sp

eed

(m/s

)

0.0

0.2

0.4

0.6

0.8

Time (s)

0 1 2 3 4 5 6 7 8 9

Sp

eed

(M/S

)

0.0

0.2

0.4

0.6

0.8

Time (s)

0 1 2 3 4 5 6 7 8 9

Sp

eed

(M/S

)

0.0

0.2

0.4

0.6

0.8

Time (s)

0 10 20 30 40 50 60 70 80

Sp

eed

(m

/s)

0.0

0.2

0.4

0.6

0.8

Figure 3: Preference for the home base quadrant (left hand panel) and total travel distance (right hand panel) are plotted for both groups. Groups were equivalent in their preference for the home base quadrant and total distance traveled.

Qua

dran

t pre

fere

nce

0.0

0.2

0.4

0.6

0.8

1.0 SHAMMS SAP

Dis

tanc

e (m

)

0

50

100

150

200

Last Stop Mean Stops First Stop

Cha

nge

in H

eadi

ng (

Deg

rees

)

0

20

40

60

80

100

120

140

160 SHAMMS SAP

Pat

h C

ircui

ty

0.0

0.2

0.4

0.6

0.8

1.0

Ma

x S

pe

ed

(m/s

)

0.0

0.2

0.4

0.6

0.8

1.0 SHAMMS SAP

Pat

h C

ircui

ty

0.0

0.2

0.4

0.6

0.8

1.0

Short Medium Long

St D

ev

Pe

ak L

oca

tion

0.00

0.05

0.10

0.15

0.20

Short Medium Long

Sto

p D

urat

ion

(s)

0

2

4

6

8

10

Max

Spe

ed (

m/s

)

0.0

0.2

0.4

0.6

0.8

1.0 SHAM MS SAP

Pa

th C

ircu

ity

0.0

0.2

0.4

0.6

0.8

1.0*

St D

ev P

eak

Loca

tion

0.00

0.05

0.10

0.15

0.20

*

Err

or in

Dis

tanc

eE

stim

atio

n

0.00

0.05

0.10

0.15

0.20

*

Cortex Hippocampus

Opt

ical

Den

sitiy

0

20

40

60

80

100

120

140 SHAMMS SAP *

-1.0 -0.6 -0.2 2.0

Ho

mew

ard

Seg

men

t D

ista

nce

Err

or

0.00

0.10

0.20

0.30

-1.0 -0.6 -0.2 2.0

0.00

0.10

0.20

0.30

-1.0 -0.6 -0.2 2.0

Ho

mew

ard

Seg

men

t D

ista

nce

Err

or

0.00

0.10

0.20

0.30

-1.0 -0.6 -0.2 2.0

0.00

0.10

0.20

0.30

Outward SegmentLinear-Angular Correlation

-1.0 -0.6 -0.2 2.0

Ho

mew

ard

Seg

men

t D

ista

nce

Err

or

0.00

0.10

0.20

0.30

Outward SegmentLinear-Angular Correlation

-1.0 -0.6 -0.2 2.0

0.00

0.10

0.20

0.30

A B

C D

A B

C D

SHAM MS SAP

All All

High Circuity High Circuity

No Stops No Stops

R=0.140 F(1,94)=1.89, p=ns

R=0.024F(1,94)=0.055, p=ns

R=0.275F(1,94)=7.667, p<.01

R=0.219 F(1,38)=1.912, p=ns

R=0.148 F(1,38)=0.847, p=ns

R=0.259 F(1,38)=2.724, p=ns