biodata - jnu.ac.in · 6 chaired key note lecture session during xxv meeting indian soc....
TRANSCRIPT
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BIODATA
1. Name of the Nominee : BirendraNathMallick
2. Date of Birth : 01. 8. 1956
3. Present Position/designation : Professor of Neurobiology
4. Official and Mailing : School of Life Sciences, JawaharlalNehruUniversity
Address New Delhi - 110 067, INDIA
Ph : 011-2670-4522 (Office); FAX : 011-2674 2558, 2674 1586;
March 2013 - Continuing Dean, School of Life Sciences, JNU
E. Mail :[email protected]; Web Page Address : http://www.jnu.ac.in/Faculty/bnmallick
5. Academic Qualification (starting from Bachelor's Degree) : ____________________________________________________________________________________
Degree Year (*delayed exam) University Division Subject/s
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B.Sc. 1978*(Batch 1977) Calcutta II Physiology (Hons), Phy&Chem
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M.Sc. 1981*(Batch 1979) Calcutta I Physiology
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Ph.D. 1986 AIIMS Neurophysiology of Sleep-Wakefulness
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D.M.S. 1979 Council of Homoeopathic Medicine (W.B.) Medicine subjects
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6. Chronology of Appointments :
______________________________________________________________________________ July 1981- August 1983 - Teaching Fellow, Department of Physiology, AIIMS
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Sept 1983- June 1986 - Senior Demonstrator, Department of Physiology, AIIMS
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June 1986 - Sept 1993 - Asstt. Prof., School of Life Sciences, JNU
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May 1987- July 1988 - Research Assoc., UCLA, USA
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March 1993 - July 1993 - VisitingAsstt. Prof., Harvard Medical School, USA
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Oct 1993 - Sept 2001 - Assoc. Professor, School of Life Sciences, JNU
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March 1995 - July 1995 - Visiting Assoc. Prof., Dept. of Neuropsychiatry, UCLA, USA
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March 1997 - July 1997 - Visiting Assoc. Prof., Dept. of Neuropsychiatry, UCLA, USA
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Oct 2001 - Continuing - Professor, School of Life Sciences, JNU
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Nov-Dec 2002 - Guest Professor, Univ of Nice Sophia-Antipolis, Faculté des Sciences, France
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SOME RELEVANT CREDENTIALS ______________________________________________________________________________
B. K. S. Medal (1978) --- B.Sc. (1st in College)
University Gold Medal (1981) --- M.Sc. (1st inCalcuttaUniversity)
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B. K. Anand Research Prize (1984) --- Association of Physiologists & Pharmacologists of India
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Shakuntala Amir Chand Award (1992) --- Indian Council of Medical Research, India
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National Bioscience Award (1999) ----- Department of Biotechnology, India
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Elected Fellow of TheNationalAcademy of Sciences (F.N.A.Sc.) (2000)
______________________________________________________________________________ Felicitedby the Department of Physiology, CalcuttaUniversity, May 5, 2000
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Shanti SwarupBhatnagar Prize (Medical Sciences, 2001)Council of Scientific & Industrial Research, India _____________________________________________________________________________________
RamendraSundar Sinha Memorial Oration (2001) ---- Physiological Society of India
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Chandra KantaDandiya Prize (2001) --- P C Dandiya Trust, India
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Elected Member of the Guha Research Conference (GRC) (2004)
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Elected Fellow of The Indian National Science Academy (F.N.A.) (2004)
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INSA Sectional Committee Member 2006-2008
______________________________________________________________________________ J. N. Mukherjee Memorial Lecture,CityCollege, Kolkata (2007)
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Member Planning Committee for SERCSchool on Neurosciences (2007-2011), DST
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Member Animal Sciences & Biotechnology Research Committee (2008-2011) CSIR
______________________________________________________________________________ Platinum Jubilee Lecture (2009), Physiological Society of India
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Elected Fellow of The Indian Academy of Sciences (F.A.Sc.) (2010)
J. C. Bose National Fellowship, DST, 2010
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Elected Fellow of the West Bengal Academy of Science and Technology (FAScT) 2010
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Associate Editor :BMC Neuroscience
Associate Editor :Frontiers in Neurology - Sleep and Circadian Rhythm
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Invitation from International Organizations for Grant reviewing/Award Selection, etc
National Science Foundation (NSF), USA (for Merit Grant reviewing); Indo-French Centre for the Promotion of Advanced Research (CEFIPRA);
Indo-US Science & Technology Forum (IUSSTF);
Human Frontier Science Program Organization (HFSPO);
----------------------------------------------------------------------------------------------------------------------- Delivered Invited Lectures at DST-INSPIRE Program at (many others invited but could not make it)
Kashmir University, Srinagar, 2010;
Pt. Ravishankar Shukla University, Raipur, 2010;
Ravenshaw University, Cuttak, 2013;
AMITY Gwalior, Jan 2014;
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UJJAIN, Feb 2014;
SES, JNU, Feb 2014
KIIT, Gurgaon, JULY 2014
Burdwan University, August 2014
NIT Sikkim, Dec 2014
_____________________________________________________________________
Member of various bodies outside JNU (CSIR; DBT; DST; ICGEB; ICMR; NII) Judge for evaluation of presentation at St. Mary’s School, New Delhi, 1993;
Member of the SRF selection Committee under CSIR;
Member of the RA selection Committee under CSIR;
Member for student Selection Committee at National Institute of Immunology, 2002;
Member for Teacher Selection Committee at KendriyaVidyalaya, 2004;
Judge for evaluation of presentation at SpringdalesSchool, DhaulaKuan, New Delhi, Aug 10, 2006;
Governor’s Nominee for Faculty selection of StateUniversity, Jan 2007;
Member GOI selection Committee for selection of Indo-Israel exchange scholars, 2008;
Member of the Senior Research Associate (Pool Officer) selection Committee under CSIR;
Member of the Examination Committee for CSIR/UGC-JRF (NET) Examination;
Member of the CSIR/UGC-NET Syllabus Revision Committee;
Member of the Examination Committee for DBT-JRF Examination (BET);
Member Scientist Selection Committee DRDO;
Member for student Selection Committee at ICGEB, 2010;
Member of the Scientific Committee for organizing 26th Round Table Conference on “Sleep Disorders” by
Ranbaxy Science Foundation;
Member Institutional Animal Ethics Committee (IAEC) of Institute of Liver and Biliary Science (ILBS),
New Delhi (2011- )
Chairman of the sub-group for proposing “Future Directions” for preparation of “National Guidelines on
Obstructive Sleep Apnea”
Judge for evaluation of presentations at Tagore International School (Greater Kailash Branch), New Delhi,
Topic “Revolutionary medical therapy to diagnose, monitor, and treat injuries and diseases while you sleep” on
Nov 8, 2012 Chairman for selection/promotion to Professorship at University outside JNU
Member for selection/promotion to Faculty positions at University outside JNU
Member Board of Studies, Amity Institute of Neuropsychology and Neurosciences, Amity Univ.,
Aug 2013 –
Member of Medical Biotechnology and Medical Nanotechnology, Sectional Committee
Bureau of Indian Standard, New Delhi.
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Member Scientific Advisory Committee (SAC) of National Brain Research Centre (NBRC)
Member S. S. Bhatnagar Award Selection Committee
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UGC Nominee - External Expert member to CAS-V Advisory Committee, Dept of Zoology, BHU
Member Board of Studies, Centre for Biological Studies, Central Univ Bihar
______________________________________________________________________________ Member Grant/Project reviewer/selection committees for
CSIR, DBT, DST, ICMR,
Indo-German projects under DST;
______________________________________________________________________________ Adhoc Peer-Reviewer for the following International Science Journals (Alphabetical list) :
African Journal of Pharmacy and Pharmacology;
Behavioural Brain Research;
Behavioural Brain Functions;
BMC Neuroscience;
Brain Research;
Brain Research Bulletin;
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Brain Research Protocol;
British Journal of Pharmacology;
Brazilian Journal of Medicine & Biomedical Research;
Developmental Brain Research,
European Journal of Neuroscience;
Frontiers in Neurology
Iranian Journal of Pharmacology & Therapeutics;
Journal of Biosciences;
Journal of Neurophysiology;
Journal of Neuroscience Research;
Journal of Physiology & Pathophysiology
Journal of Sleep Research;
Journal of Sleep Disorders & Therapy
Life Sciences;
Neuropharmacology;
Neuroscience;
Neuroscience Letters;
Pathobiology;
Pharmacology Biochemistry & Behaviour;
Pharmacological Research;
PLoS ONE;
Progress in Neurobiology;
Progress in Neuro-Psychopharmacology & Biological Psychiatry;
SCIENCE;
Sleep;
Sleep & Biological Rhythm;
Sleep & Hypnosis;
Sleep Research Online
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Adhoc Peer-Reviewer for the following National Science journals (Alphabetical list) : Indian Journal of Physiology and Pharmacology
Indian Journal of Experimental Biology
Indian Journal of Medical Research
Indian Journal of Pharmacology
Proceedings of IndianNationalScienceAcademy
---------------------------------------------------------------------------------------------------------------------- Served/Serving Editorial Board Member of
"Sleep and Hypnosis " (International Journal)
"Neurobiology of sleep-wakefulness cycle" (International Journal)
"Indian Journal of Physiology and Allied Sciences"
“Proceedings of the IndianNationalScienceAcademy”
______________________________________________________________________________ Member of International Scientific Organization :
International Advisory Board member of 5th Asian Sleep Research Society Meeting Sept 2006
Program Committee of the 9th International Congress of Behavioral Medicine Nov 29-Dec 2, 2006
_________________________________________________________________________________ Course Co-ordinator - 4th Refresher Course in Life Sciences, Academic Staff College, JNU, 1998
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Postgraduate (M.Sc. and M.D.) and Ph.D. thesis examiner for several Universities across the country
Extramural Funded Research Projects :
a) Completed : 18b) Ongoing : 1
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Ph.D. theses completed under my supervision – Eighteen (others are continuing)
M.Phil. & M.Sc. dissertation completed under my supervision – Thirty (others are continuing)
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Others short term trainee in the lab (across the country and abroad) -More than sixty
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Invited lectures during conferences/symposium or otherwise (International) :
Outside India : 43 Within India : 19
Invited lectures during conferences/symposium or otherwise (National) : >120
Other than conferences, lectures delivered at Research Organizations :
ACTREC, Bose Institute, Dabur Research Foundation, DIPAS, Dr. Reddy’s Laboratory (Hyderabad),
Institute for Fisheries (Mumbai), SAMEER (Chennai),
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Universities/Institutes : ACBR (Delhi); AIIMS; Aligarh Muslim University (Biochemistry Dept); Amity University (Biotechnology),
UP; Amity University, Gwalior, MP; Annamalai University; APS University, Rewa; Bilaspur University,
Bilaspur; Burdwan University, Burdwan; B V Patel Chest Inst.; Banaras Hindu University (Zoology Dept);
Banaras Hindu University (IMS); Calcutta University (Biochemistry); Calcutta University (Physiology); IIT
Delhi (Electrical EngDept); IIT Kanpur; Indian Statistical Institute (Cal); JamiaHamdard (New Delhi);
JamiaMilliaIslamia (New Delhi); JNCASR (Bangalore); JN Vyas University, Jodhpur; Jiwaji University
(Gwalior); Kurukshetra University; Lucknow University (Zoology); Madurai Kamraj University; National
Brain Research Centre, Gurgaon; NIT Ravangla, Sikkim; Pt. Ravishankar Shukla Univ (Raipur); Pune
University (Biotechnology); Pune University (Zoology); Ravenshaw University, Cuttack; South Asian
University; Tripura Univ. (Physiology Dept); Ujjain University, Ujjain; Vidyasagar University (Human
Physiology);
Colleges : Acharya Narendra Dev College (Delhi), City College (Kolkata), Daulat Ram College (Delhi), Sophia College
(Mumbai),
Lectures have been delivered in some schools as well e.g. NavodayaVidyalaya, Sikkim;
(Additionally, Academic Staff College Lectures – ~ 80 lectures until 2012;
PLUS lectures during Summer/winter schools/courses/workshops ~24 lectures until 2012).
Chaired session(s) during conferences/seminars/oration lectures : Co-Chair Maj. Gen. S. L. Bhatia Oration Lecture, 1993, Trivandrum
Symposium Co-Chair - 3rd World Fed Sleep Res SocMeeting,Dresden, Germany, Oct 3-9, 1999
Symposium Chair - 3rd
Asian Sleep Research Society Meeting, Bangkok, Dec 3-7, 2000
Co-ChairIndo-US Symposium on Brain Research, New Delhi, Jan 10-12, 2002
Symposium Chair - 4th
Asian Sleep Research Society Meeting, Zhuhai, China, Feb 28-Mar 2, 2004
Chaired the lecture function by Nobel Laureate Dr.Torsten Wiesel, at Delhi Univ, May 24, 2006
Session Chair during XVIII Meeting Indian Soc. Chronobiology, Nov 8-10, 2006, NEHU/Shillong
Session Chair during 4th
FIPS Meeting, Delhi Jan 11-13, 2007
Session Chair during 9th World Congress of Sleep Apnoea Meeting, March 24-28, 2009, Seoul, Korea
Session Chair during Platinum Jubilee Programme of PSI, ScienceCity, Kolkata, Nov 13, 2009
Session Chair during XXII National Conference of Indian Soc. Of Chronobiology, Dept of Zoology,
KurukshetraUniv., March 15-17, 2011
Session Chair, National Conference on Advances in Biological Sciences, Pt.RaviShankarShuklaUniversity,
Raipur, Nov 5-7, 2011
Chair at Key Note Address at theXXth Vedanta Congress, JNU Dec 28-31, 2011.
Session Chair, at XXIII meeting of ISC, APS Univ., Jodhpur; March 1-2, 2012.
Session Chair, at XXX meeting of IAN, GND Univ., Amritsar; Oct 27-30, 2012.
Inauguration of Academic Staff College Refresher Course at Burdwan University, Nov 2, 2012
Co-Chaired the Indo-Swiss Symposium session “Sleep and Depression : Biomarker and neuroplasticity”
During 1st Global Meet on BiolPsychiat, Mariott, New Delhi 25-28, Sept 2014.
Guest of Honour Amity, NOIDA during INSPIRE Camp Inauguration, Jan 2015.
Session Chair, Indian Society for Heart Research 2015, March 14-15, 2015; JNU.
Chaired session at Nalanda Tradition of Budhism in Asia, Nov 14, 2013, New Delhi
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Chaired Key note lecture session during XXV Meeting Indian Soc. Chronobiology, March 27-29,
2015, Pt. Ravi Shankar Shukla Univ., Raipur, Chhattisgarh
About Ph.D. students from this lab: - Five published papers were judged best papers and my students were awarded the
B. K. Anand Research Prize by the Association of Physiologists & Pharmacologists of India (APPI).
- R. Sriniwasan Prize by the Association of Physiologists & Pharmacologists of India (APPI).
- Several posters (students) were judged best poster/presentation during National conferences and
students/researchers were awarded.
- One student received INSA Medal for Young Scientist, 2008.
- One student received Prof LSS Kumar Memorial Award, INSA, 2008.
- Another my Ph. D. student was short listed for the INSA Medal for Young Scientist (1996), however,
due to unavoidable circumstances she couldn’t come from abroad for the final presentation/selection.
- Three of my Ph.Ds. (Post-Doc in USA) received Young Investigators’ Award by the Sleep Research
Society, USA (for work done during their post-doc period). - One student received Scopus-Elsevier (India) Award (Biological Sciences), 2008
- A large number of students/trainees from this lab have become independent
Faculty/Scientists in various Universities/Research Organizations in India and Abroad
(including Full Professor in UCLA, Associate Professor Univ of Missouri; BundelkhandUniv;
AsstProf.Univ of Michigan)
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Membership to(International Societies/Professional Bodies) : International Brain Research Organization (IBRO);
Society for Neuroscience (SFN);
Sleep Research Society, USA(SRS);
World Federation of Sleep Research Society (WFSRS) (Being a member of SRS)
Membership to (National Societies/Professional Bodies) All Life Members : Association of Physiologists and Pharmacologists of India (APPI);
Indian Association of Neurosciences (IAN);
Indian Society of Chronobiology (ISC);
Indian Science Congress Association (ISCA);
Indian Society of Cell Biology (ISCB);
Indian Society of Chemical Biology (ISCB);
Neuroscience Society of India (NSI);
Physiological Society of India (PSI);
Organizational: Organizing Secretary, 38th Annual Conference of APPI, 1992
Joint Organizing Secretary of the XI National Symposium of the ISC, 1996
Organizer one day mini-symposium on Neuroscience in SLS, JNU, April 1998 (BIC, JNU)
Organizer Biospark, SLS/JNU, 2005
Organizer Brain Awareness Programme SLS/JNU, 2006
Organizer Summer Course SLS/JNU, 2006
Organized “The journey of Four Decades of SLS: From Concept to the rise”, Feb 13-15, 2014
=======================================================================
Other Academic and Administrative responsibilities in JNU Member of JNU Academic Council (1990-1991; 2010 – 2011; 2013 - 2014)
Member of JNU Court (1990 – 1991; 2010 – 2011; 2013 - 2014)
JNU Executive Council Member 2013-2014
Provost (Paschimabad) – Appointed by the VC, JNU (2000 – 2001)
Chairman, SLS Admission Committee 2004
JNU VC’s nominee for faculty selection at various levels in JNU (on several occasions)
JNU VC’s nominee to the Academic Committee of International Centre for Genetic Engineering &
Biotechnology (ICGEB), an Institute recognized by the JNU for the award of Ph.D. degree 2010-12.
JNU VC’s nominee to the Academic Committee of Central Drug Research Institute (CDRI), Lucknow, an
Institute recognized by the JNU for the award of Ph.D. degree 2010-12.
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Chairman, JNU Liveries Committee (2010 - 2012)
Chairman of various University bodies viz.
Chair, Biosafety Committee, JNU, 2013-2014;
Chair, Animal House Advisory Committee, JNU, 2013-2014
Chair, School Level Purchase Committee, SLS, 2013-2014
Chair, Faculty Committee, SLS, 2013-2014
Chair, Special Committee, SLS, 2013-2014
Appointed member of various academic and administrative bodies/committees in JNU and SLS e.g.
Chairman/Member Graduate Advisory Committee
Chairman/Member Student-Faculty Committee
Co-PI of the BUILDER project (DBT-JNU)
Faculty In-charge of JNU Animal House 2011 - 2012
Served on several occasions as Acting Dean, School of Life Sciences, JNU
Member Institutional Ethics Review Board (IERB), JNU (2011 - )
Dean;School of Life Sciences, March 2013- Feb 2015
VC-Nominated member to Academic Committee in Centre of Science Policy Studies, JNU,
July 2013- June 2015
VC-Nominated member Academic Committee of Centre of Persian & Central Asian Studies, School of
Languages, JNU, Aug 2013- July 2015
JNU VC-nominated members of various other committees in JNU
JNU EC-nominated members of various other committees in JNU
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Extracurricular/Hobbies: As student :
President's Scout; Divisional School Team Hockey player
At Present :
Reading, Philosophy
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OVERSEAS VISIT _____________________________________________________________________________________
S.No Period Place visited Purpose of visit
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1. May 87 - July 88 UCLA, USA Research on Sleep-wakefulness
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2. July 88 (3 days) Osaka Bioscience Institute, Japan Delivered lecture
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3. March 13-17, 1993 Mauii, USA WFSRS Meeting
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4. Mar 93 - July 93 Harvard University, USA Research on Sleep-wakefulness
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5. Mar 95 July 95 Univ. of California, USA Research on Sleep-wakefulness
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6. May 30 - June 4, 95 Nashville, USA Sleep Research Society Meeting
_______________________________________________________________________________________
7. Mar 97 - July 97 UCLA, USA Research on Sleep-wakefulness
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8. June 10 - 15, 97 SanFrancisco, USA Sleep Research Society Meeting
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9. Aug 25-28, 97 Jerusalem, Israel Lecture 2nd
Asian Sleep Res Soc
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10. Oct 4-9, 99 Dresden, Germany Co-Chair symposium & lectures WFSRS Meeting
________________________________________________________________________________________
11. Oct 10-12, 99 Max Planck Institute for Psychiatry, Munich Lectures (TWO)
________________________________________________________________________________________
12. Dec 3-7, 2000 Bangkok, 3rd
Asian Sleep Res. Soc. Meet Plenary Talk & Session Chair (TWO)
_______________________________________________________________________________________
13. June 28-30, 2001 INSERM Lyon, France Lectures (TWO)
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14. July 1-6, 2001 Berlin, Germany, 7th WCBP Symposium talk
15. Nov – Dec 2002 Univ of Université de Nice Sophia-Antipolis Guest Professor
Faculté des Sciences Nice Cedex 2 France
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16. Feb 24-26, 2004 Neuro-Behavioural Biology Center Two Invited Lectures
Mahidol University, Bangkok, Thailand
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17. Feb 27-Mar 2, 2004 ASRS Meeting, Zuhai, China Plenary Talk & Session Chair (TWO Talks)
______________________________________________________________________________________
18. Mar 3-7, 2004 National Chung-Cheng University, Taiwan TWO Invited Lectures
19. Mar 3-7, 2004 Taipei Veterans General Hospital, Taiwan Invited Lecture
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20. Mar 3-7, 2004 Show Chwan Memorial Hospital, Taiwan Invited Lecture
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21. Mar 3-7, 2004 National Yang-Ming University, Taiwan Invited Lecture
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22. Feb 4-8, 2007 2nd
World Assoc. Sleep Medicine Meeting, Bangkok Plenary Symp. Lecture
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23. Oct 7-9, 2007 1st Int. Meeting on Behav Neuroscience Plenary Symp. Lectures
and Medicine, Bangkok Two lectures
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24. March 21-24, 2009 Neuro-Behavioural Biology Center Two Invited Lectures + One
class Mahidol University, Bangkok, Thailand with students
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25. March 25-28, 2009 9th World Congress on Sleep Apnea Lecture at Meet the Professor Session
Seoul, Korea (WCSA2009)
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26. March 29-31, 2009 Akita University, Japan Onelecture+One interview by Prof. Shimizu
(Prof. Shimizu, Head, Neuropsychiatry)
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27. April 1-2, 2009 Sendai Univ., Japan, Graduate Sch. Information Science, One lecture
And Dept of Pharmacology
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28. April 3-5, 2009 Osaka Bioscience Institute, Japan One lecture
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29. April 6-7, 2009 Korea University, Ansan Campus, Seoul One lecture
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30. April 6-7, 2009 Seoul National University, Korea One lecture
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31. April 8-13, 2009 Beijing University, Peiking, China Two lectures
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32. Oct 22-24, 2009 The Chinese Univ of HongKong, Faculty of Medicine Two lectures
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33. Oct 25-27, 2009 6th ASRS Meeting, Osaka, Japan Symposium lecture
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34. Oct 26, 2009 Shiga Univ sponsored lecture at Osaka, Japan One lecture
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35. Oct 30, 2009 Shiga Univ. sponsored lecture at Okinawa, Japan One lecture
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36. Oct 19, 2011 WFSRS Meeting, Kyoto, Japan (Oct 16-20, 2011) One Lecture
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(Total 43 lectures)
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LIST OF PUBLICATIONS
A. Research papers : 1. Mallick,B.N., Chhina,G.S., Sundaram,K.R., Singh,B. and Mohan Kumar, V. Activity of preoptic
neurons during synchronization and desynchronization, Exp. Neurol., 81 (1983) 586 - 597.
2. Mohan Kumar,V., Mallick,B.N., Chhina,G.S. and Singh,B., Influence of ascending reticular
activating system on preoptic neuronal activity, Exp. Neurol., 86 (1984) 40 - 52.
3. Mallick,B.N., Mohan Kumar,V., Chhina,G.S. and Singh,B., Responses of preoptic neurons to
stimulation of caudal and rostral brain stem reticular structures, Brain Res.Bull., 13 (1984) 353 - 356.
4. Mohan Kumar,V., Mallick,B.N., Chhina,G.S. and Singh,B., Alterations in preoptic unit activity on
stimulation of caudal brain stem synchronizing structures, Exp.Neurol., 89 (1985) 304 - 313.
5. Mallick,B.N., Mohan Kumar,V., Chhina,G.S. and Singh,B., Comparison of rostro-caudal brain stem
influence on preoptic neurons and cortical EEG, Brain Res. Bull., 16 (1986) 121-125.
6. Mohan Kumar,V., Mallick,B.N., Chhina,G.S. and Singh,B., Correlation of preoptic neuronal
activity with spontaneous and induced cortical EEG change, Ind.J.Physiol. Pharmacol., 32
(1988) 83-92.
7. Wu,M.F., Mallick,B.N. and Siegel,J.M., Lateral geniculate spikes, muscle atonia and startle response
elicited by auditory stimuli as a function of stimulus parameters and arousal state, Brain Res.,
499 (1989) 7-17.
8. Mallick,B.N., Siegel,J.M. and Fahringer,H., Changes in pontine unit activity after REM sleep
deprivation, Brain Res., 515 (1990) 94-98.
9. Alam,M.N. and Mallick,B.N., Differential acute influence of medial and lateral preoptic areas on sleep-
wakefulness in freely moving rats, Brain Res., 525 (1990) 242-248.
10. Mallick, B. N. and Alam, M. N., Medial preoptic area affects sleep independent of associated body
temperature change in free moving rats, Brain Res. Bull., 26 (1991) 215-218.
11. Thakkar, M. and Mallick, B. N., Effect of REM sleep deprivation on rat brain acetyl-cholinesterase,
Pharmacol.Biochem. Behav., 39 (1991) 211-214.
12. Mallick, B. N. and Thakkar, M., Short term REM sleep deprivation increases acetyl- cholinesterase
activity in the medulla of rats, Neurosci. Lett., 130 (1991) 221-224.
13. Mallick, B. N., Fahringer, H., Wu, M. F. and Siegel, J. M., REM sleep deprivation reduces
auditory evoked inhibition of dorsolateral pontine neurons, Brain Res., 552 (1991) 333-337.
14. Alam,M.N. and Mallick,B.N., Differential influence of medial and lateral preoptic areas on body
temperature in conscious and unconscious rats, Brain Res., 566 (1991) 303-307.
15. Mallick, B. N. and Thakkar, M., Effect of REM sleep deprivation on molecular forms of
acetylcholinesterase, Neuroreport, 3 (1992) 676-678.
16. Mallick, B. N.,Alam, M. N., Different types of norepinephrinergic receptors are involved in preoptic
area mediated independent modulation of sleep-wakefulness and body temperature, Brain Res., 591
(1992) 8-19.
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17. Gulyani, S. and Mallick, B. N., Effect of rapid eye movement sleep deprivation on rat brain Na-K
ATPase activity, J.Sleep Res., 2 (1993) 45-50.
18. Thakkar, M. and Mallick, B. N., Effect of REM sleep deprivation on rat brain monoamine
oxidases, Neuroscience, 55 (1993) 677-683.
19. Mallick, B. N. and Gulyani, S., Rapid eye movement sleep deprivation increases chloride sensitive
ATPase activity in the rat brain, Pharmacol. Biochem.Behav., 45 (1993)359-362.
20. Thakkar, M. and Mallick, B. N., Rapid eye movement sleep deprivation induced changes inglucose
metabolic enzymes in rat brain, Sleep 16 (1993) 691-694.
21. Alam, M. N. and Mallick, B. N., Role of lateral preoptic area alpha-1 and alpha-2 adrenoceptors in
sleep-wakefulness and body temperature regulation, Brain Res. Bull., 35 (1994) 171 - 177.
22. Gulyani, S. and Mallick, B. N., Possible mechanism of rapid eye movement sleep deprivation induced
increase in Na-K ATPase activity, Neuroscience, 64 (1995) 255 - 260.
23. Mallick, B. N., Thakkar, M. and Gangabhagirathi, R. Rapid eye movement sleep deprivation
decreases membrane fluidity in the rat brain, Neurosci. Res., 22 (1995) 117-122.
24. Thakkar, M. and Mallick, B. N., Effect of rapid eye movement sleep deprivation on 5'nucleotidase
activity in the rat brain, Neurosci. Lett. 206 (1996) 177-180.
25. Singh, S. and Mallick, B. N. Mild electrical stimulation of pontinetegmentum around locus coeruleus
reduces rapid eye movement sleep in rats, Neurosci. Res., 24 (1996) 227-235.
26. Mallick, B. N. and Gulyani, S., Alterations in synaptosomal calcium concentrations after rapid eye
movement sleep deprivation in rats, Neuroscience, 75 (1996) 729-736.
27. Mallick, B. N. and Joseph, M. M., Role of cholinergic inputs to the medial preoptic area in
regulation of sleep-wakefulness and body temperature in freely moving rats, Brain Res. 750
(1997) 311-317.
28. Kaur, S., Saxena, R. N. and Mallick, B. N., GABA in locus coeruleus regulates spontaneous rapid eye
movement sleep by acting on GABAA receptors in freely moving rats, Neurosci. Lett. 223 (1997) 105-
108.
29. Mallick, B. N., Thankachan, S. and Islam, F., Differential responses of brain stem neurons during
spontaneous and stimulation induced desynchronization of the cortical EEG in freely moving cats, Sleep
Res. Online, 1 (1998) 132-146.
30. Mallick, B. N. and Joseph, M. M., Adrenergic and cholinergic inputs in preoptic area of rats
interact for sleep-wake-thermo-regulation, Pharmacol. Biochem.Behav. , 61 (1998) 193-199.
31. Adya, A. and Mallick, B. N. , Comparison of Na-K ATPase activity in rat brain synaptosome under
various conditions, Neurochem. Intnl. , 33 (1998) 283-286.
32. Thankachan, S., Islam F. and Mallick B. N., Adrenergic and cholinergic modulation of spontaneous
and brain stem reticular formation stimulation induced desynchronization of the cortical EEG in freely
moving behaving cats, Sleep and Hypnosis, 1 (1999) 14-21.
33. Ali, M., Jha, S. K., Kaur, S. and Mallick, B. N., Role of GABA-A receptor in the preoptic area in the
regulation of sleep-wakefulness and rapid eye movement sleep, Neurosci. Res., 33 (1999) 245-250.
34. Mallick, B. N. and Adya, H. V. A., Norepinephrine induced alpha-adrenoceptor mediated increase in rat
brain Na-K ATPase activity is dependent on calcium ion, Neurochem. Intnl.34 (1999) 499 - 507.
35. Adya, A. and Mallick, B. N.Uncompetitive stimulation of rat brain Na-K ATPase activity by rapid
eye movement sleep deprivation, Neurochem. Intnl., 36 (2000) 249-253.
12
36. Das, M., Mallick, B. N., Dasgupta, S. C. and Gomes, A., A sleep inducing factor from common indian
toad (Bufomelanostictus, Schneider) skin extract, Toxicon, 38 (2000) 1267- 1281.
37. Mallick, B. N. , Adya, H. V. A. and Faisal, M., Norepinephrine stimulated increase in Na-K ATPase
activity in the rat brain is mediated through -1Aadrenoceptor possibly by dephosphorylation of the
enzyme, J. Neurochem., 74 (2000) 1574-1578.
38. Gulyani, S., Majumdar, S. and Mallick, B. N., Rapid Eye Movement Sleep and Significance of its
Deprivation Studies - A Review, Sleep and Hypnosis, 2 (2000) 49-68.
39. Sanan, N., Mallick, B. N. and Sopory, S. Electrical signal from root to shoot in Sorghum bicolor:
induction of leaf opening and evidence for fast extracellular propagation, Plant Sci., 160 (2001) 237-
245.
40. Mallick, B. N., Kaur, S. and Saxena, R. N. Interactions between cholinergic and GABA-ergic
neurotransmitters in and around the locus coeruleus for the induction and maintenance of rapid eye
movement sleep in rats, Neuroscience, 104 (2001) 467-485.
41. Thankachan, S., Islam, F. and Mallick, B. N., Role of Wake inducing Brain Stem area on Rapid Eye
Movement Sleep regulation in freely moving cats, Brain Res. Bull., 55 (2001) 43-49.
42. Jha, S. K., Islam, F. and Mallick, B. N., GABA exerts opposite influence on warm and cold sensitive
neurons in medial preoptic area in rats, J. Neurobiol., 48 (2001) 291-300.
43. Kaur, S., Saxena, R. N. and Mallick, B. N. GABA-ergic neurons in prepositushypoglossi regulate REM
sleep by its action on locus coeruleus in freely moving rats, Synapse, 42 (2001) 141-150
44. Jha, S. K., Yadav, V. and Mallick, B. N.GABA-A receptors in mPOAH simultaneously regulate sleep and
body temperature in freely moving rats, Pharmacol. Biochem. Behav., 70 (2001) 115-121.
45. Mallick, B. N., Jha, S. K. and Islam, F. Presence of -1 adrenoreceptors on thermosensitive neurons in
the medial preoptico-anterior hypothalamic area in rats, Neuropharmacology, 42 (2002) 697-705.
46. Mallick, B. N., Majumdar, S., Yadav, V., Faisal, M., Madan, V. and Pal, D. Role of norepinephrine in
the regulation of rapid eye movement sleep, J. Biosci. 27 (2002) 539 – 551.
47. Majumdar, S .andMallick, B. N. Increased Levels of Tyrosine Hydroxylase and Glutamic Acid
Decarboxylase in Locus Coeruleus Neurons after Rapid Eye Movement Sleep Deprivation in Rats,
Neurosci. Lett. 338 (2003) 193-196.
48. Majumdar, S., Faisal, M., Madan V. and Mallick, B. N., Increased Turnover of Na-K ATPase
Molecules in the Rat Brain After Rapid Eye Movement Sleep Deprivation, J. Neurosci. Res. 73 (2003)
870 - 875.
49. Mallick, B. N., Jha, S. K. and Islam, F., Wakefulness inducing area in the brainstem excites warm
sensitive and inhibits cold sensitive neurons in the medial preoptic area in anesthetized rats, Synapse 51
(2004) 59-70.
50. Mallick, B. N., Thankachan, S. and Islam, F., Influence of hypnogenic brain areas on wakefulness and
REM sleep related neurons in the brain stem of freely moving cats, J.Neurosci. Res., 75 (2004) 133-
142.
51. Kaur, S., Panchal, M., Faisal, M., Madan, V., Nangia, P., and Mallick, B. N., Long Term Blocking of
GABA-A receptor in Locus Coeruleus by Bilateral Microinfusion of Picrotoxin Reduced Rapid Eye
Movement Sleep and Increased Brain Na-K ATPase Activity in Freely Moving Normally Behaving
Rats, Behav. Brain Res., 151 (2004) 185-190.
52. Pal, D. and Mallick, B. N.GABA in pedunculopontinetegmentum regulates spontaneous rapid eye
movement sleep by acting on GABAAreceptors in freely moving rats, Neurosci. Lett.365 (2004):200 -
13
204.
53. Mallick, B. N., Singh, S. and Pal, D. Role of alpha and beta adrenoceptors in locus coeruleus
stimulation induced reduction in rapid eye movement sleep in freely moving rats, Behav. Brain Res.
158 (2005) 9-21.
54. Majumdar, S. and Mallick, B. N., Cytomorphometric Changes in Rat Brain Neurons after Rapid Eye
Movement Sleep Deprivation, Neuroscience, 135 (2005) 679 - 690.
55. Pal, D., Madan V. and Mallick B. N.Neural Mechanism of Rapid Eye Movement Sleep Generation :
Cessation of Locus Coeruleus Neurons is a Necessity, Acta Physiol. Sinica, 57 (2005) 401-413.
56. Pal, D. and Mallick, B. N.Role of Noradrenergic and GABA-ergic inputs in
PedunculopontineTegmentum for Regulation of Rapid Eye Movement Sleep in Rats,
Neuropharmacology 51 (2006)1-11.
57. Biswas, S., Mishra, P. and Mallick, B. N., Increased Apoptosis in Rat Brain after Rapid Eye Movement
Sleep Loss, Neuroscience 142 (2006) 315-331.
58. Ramachandran, V., Subbarao, N. and Mallick, B. N., Insilico modeling of α1A-adrenoceptor:
Interaction of its normal and mutated active sites with noradrenaline as well as its agonist and
antagonist, Am. J. Biochem. Biotech., 3 (2007) 216-224.
59. Pal, D. and Mallick, B. N. , Neural Mechanism of Rapid Eye Movement Sleep Generation : with
reference to REM-OFF Neurons in Locus Coeruleus, Ind. J. Med. Res. 125 (2007) 721 - 739.
60. Das, G. and Mallick, B. N., Noradrenaline acting on 1-adrenoceptor mediates REM sleep deprivation
induced increased membrane potential in rat brain synaptosomes, Neurochem. Intnl., 52(2008)734-740.
61. Das, G., Gopalakrishnan, A., Faisal, M. and Mallick, B. N., Stimulatory Role of Calcium in Rapid Eye
Movement Sleep Deprivation Induced Noradrenaline Mediated Increase in Na-K-ATPase Activity in
Rat Brain, Neuroscience, 155 (2008) 76 - 89.
62. Md. Alam A., and Mallick, B. N., Glutamic acid stimulation of the perifornical-lateral hypothalamic
area promotes arousal and inhibits non-REM/REM sleep, Neurosci. Lett., 439 (2008) 281-286.
63. Maiti, P., Singh, S. B., Mallick, B. N., Muthuraju, S. and Ilayazhagan, G. High altitude memory
impairment is due to neuronal apoptosis in hippocampus, cortex and striatum. J. Chem. Neuroanat., 36
(2008) 227-238.
64. Jha, S. and Mallick, B. N. , Presence of α1 NE-ergic and GABA-A receptors on
mPOAHthermosensitive neurons and their role in integrating brainstem ARAS inputs in
thermoregulation in rats, Neuroscience,158 (2009) 833–844.
65. Baskey, G., Singh, A., Sharma, R. and Mallick, B. N., REM sleep deprivation induced noradrenaline
stimulates neuronal and inhibits glial Na-K ATPase in rat brain :in vivo and in vitro studies,
Neurochem. Intnl.,54 (2009) 65 – 71.
66. Jaiswal, M. K. and Mallick, B. N., Prazosin modulates rapid eye movement sleep deprivation-induced
changes in body temperature in rats, J. Sleep Res., 18 (2009) 349 - 356.
67. Pal, D. and Mallick, B. N., GABA in pedunculopontinetegmentum increases rapid eye movement sleep
in freely moving rats: Possible role of GABA-ergic inputs from substantianigra pars reticulate,
Neuroscience, 164 (2009) 404 - 414.
68. Jaiswal, M. K., Dvela, M., Lichtstein, D. and Mallick, B. N., Endogenous ouabain-like compounds in
locus coeruleus modulate rapid eye movement sleep in rats, J. Sleep Res., 19 (2010) 183 – 191.
14
69. Mallick, B. N., Singh, S. and Singh, A. Mechanism of noradrenaline induced stimulation of Na-K
ATPase activity in the rat brain : implications on REM sleep deprivation induced increase in brain
excitability, Mol. Cell. Biochem. 336 (2010) 3 -16.
70. Mallick, B. N. The Mechanism and Role of REM Sleep. Interviewed by Prof. T. Shimizu, Akita
University, Japan (Courtesy Elsevier Press, Japan). Jap. J. Sleep Med. 4 (2010) 105 - 111.
71. Herholz, J. Crisponi, L., Mallick B. N. and Rutsch, F. Successful treatment of cold-induced sweating in
Crisponi syndrome and its possible mechanism of action, Dev. Med. & Child Neurol. 52 (2010) 494-
497.
72. Ranjan, A., Biswas, S. and Mallick, B. N. Cytomorphometric changes in the dorsal raphe neurons after
rapid eye movement sleep deprivation are mediated by noradrenalin in rats, Behav. Brain Func. 6
(2010) 62 [doi:10.1186/1744-9081-6-62].
73. Ranjan, A. and Mallick, B. N., A modified method for consistent and reliable Golgi-Cox staining in
significantly reduced time, Front. Neurol. (Sleep and Chronobiol.) 1 (2010) 157.
74. Mallick, B. N., Singh, A. REM Sleep Loss Increases Brain Excitability : Role of Noradrenalin and its
Mechanism of Action, Sleep Med. Rev.15 (2011) 165-178.
75. Mallick, B. N., Singh, A. and Khanday, M. A. Activation of inactivation process initiates rapid eye
movement sleep, Prog. Neurobiol. 97 (2012) 259-276.
76. Mallick, B. N., Sleep as Tax Payment, J. Sleep Disorders &Ther. 1 (2012) : e110.doi:10.4172/2167-
0277.1000e110 (editorial).
77. Singh, S., Amar, M. and Mallick, B. N., Rapid eye movement sleep deprivation modulates SynapsinI
expression in rat brain, Neurosci. Lett. 520 (2012) 62-66.
78. Bókkon, I. and Mallick, B. N., Activation of retinotopic areas is central to REM sleep associated
dreams, Activitas Nervosa Superior (ActivNerv Super – Praha) 54 (2012) 10-25.
79. Ranjan, A. and Mallick, B. N., Differential staining of glia and neurons by modified Golgi-Cox Method,
J. Neurosci. Meth. 209 (2012) 269 – 279.
80. Kumar, R., Bose, A. and Mallick, B. N., A mathematical model towards understanding the mechanism
of neuronal regulation of wake-NREMS-REMS states, PLoS ONE (2012) 7(8) : e42059. doi : 10.1371/
journal pone.0042059.
81. Singh, A., Subhashini, N., Sharma, S. and Mallick, B. N., Involvement of the <alpha>1-adrenoceptor in
sleep-waking and sleep loss-induced anxiety behavior in zebrafish, Neuroscience, 245 (2013) 136-147.
doi: 10.1016/j.neuroscience.2013.04.026. Epub 2013 Apr 22
82. Patri, M., Singh, A. and Mallick, B. N. Protective role of noradrenalin on Benzo[a]pyrene induced
learning impairment in developing rat, J. Neurosci. Res., 91 (2013) 1450 -1462.
83. Bokkon, I., Mallick, B. N. and Tuszynski, J. A. Near death experiences: A multidisciplinary
hypothesis. Front. Hum. Neurosci. 7 (2013) 533. doi: 10.3389/fnhum.2013.00533 (pp 1-11).
84. Mallick, B. N. Stress in biological research, J. Sleep Disorders &Ther. 2 (2013) 137. doi:10.4172/2167-
0277.1000137
85. Kumar, R., Ramaswamy, R. and Mallick, B. N.Local properties of vigilance states: EMD analysis of
EEG signals during sleep-waking states of freely moving rats, PLoS ONE; 2013 Oct 22;8(10):e78174.
doi: 10.1371/journal.pone.0078174. eCollection 2013.
15
86. Ranjan, A., Behari, J. and Mallick, B. N., Cytomorphometric changes in hippocampal CA1 neurons
exposed to simulated microgravity using rats as model, Front. Neurol. (Sleep and Chronobiol.)2014
May 20;5:77. doi: 10.3389/fneur.2014.00077. eCollection 2014.
87. Choudhary, R. C., Khanday, M. A., Mitra, A. and Mallick, B. N., Perifornicalorexinergic neurons
modulate REM sleep by influencing locus coeruleus neurons in rats, Neuroscience, 279 (2014) 33-43.
88. Sharma, S. K., Katoch, V. M., Kadhiravan A. M., Elavarasi, A., Ragesh R, Nischal, N., Sethi, P.,
Behera, D., Bhatia, M., Ghoshal, A., Gothi, D., Joshi, J., Kanwar, M.S., Kharbanda, O.P., Kumar, S.,
Mohapatra, P.R., Mallick, B.N., Mehta, R., Prasad, R., Sharma, S. C., Shukla, G., Suri, J. C.,
Vengamma, B., Grover, A., Vijayan, V. K., Ramakrishnan, N., Gupta, R. Consensus and Evidence-
Based INOSA Guidelines 2014 (First Edition), Ind. J. Med. Res. 140 (2014) 451-468.
89. Singh, A. and Mallick, B. N., Targeting modulation of noradrenalin release in the brain for amelioration
of REMS-loss associated effects; J Transl. Intern. Med., 3 (2015) 8-16.
90. Mehta, R., Khanday, M. A. and Mallick, B. N., REM sleep loss associated changes in orexin-A
levels in discrete brain areas in rats, Neurosci. Lett., 590 (2015) 62-67.
91. Mehta, R., Singh, A., Bókkon, I. and Mallick, B. N., REM sleep and its loss-associated epigenetic
regulation with reference to noradrenalin in particular, Curr. Neuropharmacol. (2015) in press.
Research Gate : All-time publication downloads
FROM : https://www.researchgate.net/profile/Birendra_Mallick/stats/publication_downloads May 12, 2015 Downloads
Differential staining of glia and neurons by modified Golgi-Cox method
Amit Ranjan, BirendraNathMallick
Journal of neuroscience methods 06/2012; 209(2):269-79. DOI:10.1016/j.jneumeth.2012.06.023
4,063
Near death experiences: A multidisciplinary hypothesis.
IstvanBokkon, Birendra N Mallick, Jack A Tuszynski
Frontiers in Human Neuroscience 08/2013; DOI:10.3389/fnhum.2013.00533.
201
Activation of inactivation process initiates rapid eye movement sleep
BirendraNathMallick, Abhishek Singh, Mudasir Ahmad Khanday
Progress in Neurobiology 04/2012; 97(3):259-76. DOI:10.1016/j.pneurobio.2012.04.001
199
Local Properties of Vigilance States: EMD Analysis of EEG Signals during Sleep-Waking
States of Freely Moving Rats
Rupesh Kumar, Ram Ramaswamy, BirendraNathMallick
PLoS ONE 10/2013; 8(10):e78174. DOI:10.1371/journal.pone.0078174
118
Neural mechanism of rapid eye movement sleep generation: Cessation of locus coeruleus
neurons is a necessity.
Dinesh Pal, Vibha Madan, BirendraNathMallick
Sheng li xuebao: [ActaphysiologicaSinica] 09/2005; 57(4):401-13.
94
A Modified Method for Consistent and Reliable Golgi–Cox Staining in Significantly Reduced
Time
Amit Ranjan, BirendraNathMallick
Frontiers in Neurology 12/2010; 1:157. DOI:10.3389/fneur.2010.00157
69
16
May 12, 2015 Downloads
Near death experiences: a multidisciplinary hypothesis
IstvánBókkon, Birendra N Mallick, Jack A Tuszynski
Frontiers in Human Neuroscience 09/2013; 7:533. DOI:10.3389/fnhum.2013.00533
61
Effect of rapid eye movement sleep deprivation on rat brain NaK ATPase activity
S. GULYANI, B. N. MALLICK
Journal of Sleep Research 03/1993; 2(1):45-50. DOI:10.1111/j.1365-2869.1993.tb00060.x
59
Neural mechanism of rapid eye movement sleep generation with reference to REM-OFF
neurons in locus coeruleus.
Dinesh Pal, BirendraNathMallick
The Indian Journal of Medical Research 07/2007; 125(6):721-39.
52
In silicoModeling of 1A-Adrenoceptor: Interaction of its Normal and Mutated Active Sites
with Noradrenaline as well as its Agonist and Antagonist
VijayanRamchandran, Subbarao Naidu, BirendraNathMallick
American Journal of Biochemistry and Biotechnology 04/2007; 3(4).
DOI:10.3844/ajbbsp.2007.216.224
52
Cytomorphometric changes in the dorsal raphe neurons after rapid eye movement sleep
deprivation are mediated by noradrenalin in rats.
Amit Ranjan, Sudipta Biswas, Birendra N Mallick
Behavioral and Brain Functions 10/2010; 6:62. DOI:10.1186/1744-9081-6-62
51
A mathematical model towards understanding the mechanism of neuronal regulation of wake-
NREMS-REMS states.
Rupesh Kumar, Amitabha Bose, BirendraNathMallick
PLoS ONE 08/2012; 7(8):e42059. DOI:10.1371/journal.pone.0042059
44
REM sleep loss associated changes in orexin-A levels in discrete brain areas in rats
Rachna Mehta, Mudasir Ahmad Khanday, BirendraNathMallick
Neuroscience Letters 01/2015; 590. DOI:10.1016/j.neulet.2015.01.067
43
SCOPUS CITATION ANALYSIS Key words :Mallick, B., School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
Citations (April 2015) <2011 2011 2012 2013 2014
897 135 142 76 97
h index = 23
17
B. Book chapters :
1. Mohan Kumar,V., Chhina,G.S., Mallick,B.N., Datta,S., Bagga,N. and Singh,B., Preoptic area in sleep-
wakefulness. In: Motivational and emotional stress. Ed: K.V.Sudakov, USSR Academy of Medical
Sciences, 1984, p. 67-76.
2. Mallick, B. N. and Alam, M. N., Sleep-awake-temperature regulation by medial and lateral preoptic
areas. In : Advances in Physiological Sciences, Eds. S. K. Manchanda, W. Selvamurthy, and V. Mohan
Kumar, McMillan India, pp. 575-586, 1992.
3. Mallick, B. N. and Alam, M. N., Independent regulation of sleep-wakefulness-body temperature by the
medial preoptic area. In : Sleep-Wakefulness, Eds. V. Mohan Kumar, U. Nayar, H. N. Mallick, Wiley
Eastern, pp. 41-47, 1993.
4. Mallick, B. N., Thakkar, M, and Gulyani, S., Rapid eye movement sleep deprivation induced alteration
in neuronal excitability - possible role of norepinephrine. In : Environment and Physiology, Eds. B. N.
Mallick and R. Singh, Narosa Publishing House, 1994 pp. 196-203.
5. Mallick, B. N., Can yoga help improve sleep loss related problems? Proceedings of the World
Householders' Yoga: Conference on sane living, Dec 25-26, 1997, Bombay, India 1997, pp. 85-88.
6. Mallick, B. N., S. Kaur, S. K. Jha and Siegel, J. M., Possible role of GABA in regulation of REM sleep
with special reference to REM-off neurons. In : Rapid Eye Movement Sleep, eds. B. N. Mallick and S.
Inoue, Marcel Dekker (and also by Narosa Publishing House, New Delhi), pp. 153 - 166, 1999.
7. Mallick, B. N.,Adya, A. and Thankachan. S. REM sleep deprivation alters factors affecting neuronal
excitability : Role of norepinephrine and its mechanism of action. In : Rapid Eye Movement Sleep, eds.
B. N. Mallick and S. Inoue, Marcel Dekker (and also by Narosa Publishing House, New Delhi) pp. 338
- 354, 1999.
8. Mallick, B. N., Kaur, S., Thankachan, S. and Jha, S. K. Use of bio-physical correlates to elucidate
neural regulation of some physiological phenomena. In : Biophysical process in Living Systems. Oxford
University Press & IBH Publishers, New Delhi, ed. P. PardaSaradhi, pp. 327-342, 2001.
9. Mallick, B. N. and Thankachan, S., Role of sleep and wake areas of the brain stem in the regulation of
REM Sleep, In : Trends in Physiological Sciences: Cells to Systems, Vallabhbhai Patel Chest Institute,
Univ of Delhi, Delhi, ed. Md. Fahim, pp. 299-316, 2002.
10. Mallick, B. N., Madan, V. and Faisal, Mohd. Biochemical Changes. In : Sleep Deprivation : Basic
Science, Physiology and Behavior, Ed : C. A. Kushida, Marcel Dekker, Inc, USA, 2005, pp. 339-357.
11. Mallick, B. N., Jha, S. K. and Madan V. Role of Norepinephrine in Thermoregulation during Rapid
Eye Movement Sleep and its Deprivation. In :"Molecular and cellular Biology" Eds. M. K. Thakur,
Narosa, New Delhi, 2005; pp. 39-54.
12. Mallick B. N., Madan, V. Pal, D. and Baskey, G. C. Rapid eye movement (REM) sleep physiology and
effects of its deprivation, Proceedings of the Sleep Medicine in the 21st Century, Dept of Neurology,
AIIMS, New Delhi, Feb 11-12, 2005.
13. Mallick, B. N., Kaur, S., Thankachan, S. and Pal, D. Role of Wakefulness Area in the Brainstem
Reticular Formation in Regulating Rapid Eye Movement Sleep. In : Sleep and Sleep Disorders : A
Neuropsychopharmacological Approach, Eds. Lader M., Cardinali D. P. and Pandi-Perumal, S. R.,
Landes Bioscience/Eurekah.com and Springer Science+Business Media, Inc Publisher, George Town,
Texas, USA, 2006; p. 36-42.
18
14. Mallick, B. N., Madan V. and Pal, D. Locus coeruleus and adrenergic modulation of rapid eye
movement sleep. In : Neuroendocrine Correlates of Sleep/Wakefulness, eds. D. Cardinali and S. R.
Pandi-Perumal Springer Science+Business Media, Inc., New York, USA, pp. 163-178, 2006.
15. Mallick, B. N., Madan V. and Jha, S. Rapid Eye Movement sleep regulation by modulation of
noradrenergic system. In : The Neurochemistry of Sleep and Wakefulness, eds. M. Monti, C. Sinton, S.
R. PandiPerumal, Cambridge University Press, pp. 59-81, 2008.
16. Pal, D. and Mallick, B. N. GABA-ergic modulation of pontine cholinergic and noradrenergic neurons for rapid
eye movement sleep generation. In : GABA and Sleep: Molecular, Functional and Clinical Aspects, eds.Jame M.
Monti, S.R.Pandi Perumal and Hanns Mohler, Springer, Basel, pp.199–212, 2010.
17. Jha, S. and Mallick, B. N.REM sleep regulation : Relationship with non-REM sleep and
wakefulness. In : Rapid Eye Movement Sleep : Regulation and Function, eds. B. N. Mallick, S. R.
Pandi-Perumal, R. W. McCarley and A. R. Morrison, Cambridge University Press, London, United
Kingdom, pp. 173-182, 2011.
18. Madan, V. and Mallick, B. N.REM sleep maintains brain excitability. In : Rapid Eye Movement Sleep
: Regulation and Function, eds. B. N. Mallick, S. R. Pandi-Perumal, R. W. McCarley and A. R.
Morrison, Cambridge University Press, London, United Kingdom, pp. 359 – 367, 2011.
19. Mallick, B. N.andMukhopadhyay, A. K. Rapid Eye Movement Sleep and Dream Sleep : Are they
Identical? Exploring the conceptual developments in the Upanishads and the present knowledge
based on neurobiology of sleep. In : Rapid Eye Movement Sleep : Regulation and Function, eds. B. N.
Mallick, S. R. Pandi-Perumal, R. W. McCarley and A. R. Morrison, Cambridge University Press,
London, United Kingdom, pp. 21 – 30, 2011.
20. Mallick, B. N., Singh, A., Khanday, M. A. and Kumar, R. Neural mechanism of REM sleep
regulation. Proceedings of Ranbaxy Science Foundation, XXVIth Round Table Conference on Sleep
Disorder A Wake Up Call. 2011 (in press).
21. Mallick, B. N., Singh, A., Ranjan, A. and Srivastava, H. K. Neural regulation of REMS : critical role
of GABA-ergic inhibition. In : Rapid Eye Movement Sleep: New Research; Editors: Kiyomi Bando
and AitoHotate, Nova Sciences Publishers, Inc., Hauppauge, New York, USA, pp. 35 – 58, 2012.
22. Mallick, B. N., Dutta, A., Gupta, K. and Singh, A. Contribution of Animals in Health Research :
Emphasis on Brain Research. In : Animal Experiments : A Perspective, published by INSA, New
Delhi, pp. 112-128, 2012.
23. Mallick, B. N., Singh, A., Ranjan, A. and Srivastava, H. K. Neural regulation of REMS : critical role
of GABA-ergic inhibition. In : REM Sleep : Characteristics, Disorders and physiological effects;
Editors: Chelsea L Saylor, Nova Medical (Nova Sciences Publishers, Inc.), New York, USA, pp. 67 –
98, 2014. (Reproduced version)
24. Mallick, B. N., khanday, M. A. and Singh, A., Orexin induced modulation of REM sleep and its loss
associated patho-physiological changes are mediated through locus coeruleus, in Orexins and Sleep:
molecular, functional, and clinical aspects, Eds. Sakurai, T., Monti, J. M. and Pandi-Perumal, S. R.,
Springer, Switzerland; 2015, pp. (in press).
25. Amar, M., Singh, A. and Mallick, B. N.; Regulation of brain Na-K ATPase activity by noradrenaline
with particular reference to normal and altered rapid eye movement sleep. In :Regulation of ATPases;
Eds : SajalChakraborti &Naranjan S Dhalla, Springer, 2015 (in press).
C. Mallick, B. N. GABA in locus coeruleus in REMS regulation, J. Sleep Dis. Therap. (PPT presentation);
http://omicsgroup.org/editor-biography/Birendra_Nath_Mallick/
19
D. Book Review :
1. Book Name : The Golden Age of Rapid Eye Movement Sleep Discoveries 1965-1966; by Claude
Gottesmann, Nova, New York, 2005. Published in Sleep and Hypnosis Sleep and Hypnosis, 8 (2006) 71
- 72.
2. Reviewed Book proposal from Garland Science (Taylor and Francis Group) 2012
E. Books edited/written : 1. Mallick, B. N. and Singh, R. (1994) Environment and Physiology, New Delhi. Narosa Publishing
House, 278 p.
2. Mallick, B. N., and Inoue, S. (1999)Rapid Eye Movement Sleep, Marcel Dekker Inc, USA, 419 p.
3. Mallick, B. N., (2001) Sleep-Wakefulness, National Book Trust, India (Popular Book-For common
public).
4. Mallick, B. N., Pandi-Perumal, S. R., McCarley, R.W. and Morrison, A. R. (2011) Rapid Eye
Movement Sleep : Regulation and Function, Cambridge University Press, London, United
Kingdom, 478 p.
F (i) Structure Deposited in the data bank :
'Homology Modeling of Alpha1A-Adrenoreceptor '
RCSB ID :rcsb 035534; PDB ID : code 2F75
Vijayan, R., Subbarao, N. and Mallick B. N.
(ii) Structure Deposited in the data bank :
“Homology Modeling of Beta-1 Adrenergic Receptor”
RCSB ID :rcsb; PDB ID : code 2FF9
Vijayan, R., Subbarao, N. and Mallick B. N.
G. Patent Information :
Title of invention : A Method for diagnosis of REM Sleep loss by blood protein estimation.
Patent No. : 7,125,724 Issue Date of Patent : Oct 24, 2006
20
Brief Description of B. N. Mallick’s Research Contribution
Rapid Eye Movement (REM) sleep is a unique phenomenon expressed during sleep and was objectively
identified based on electrophysiological characteristic signals recorded from the scalp, eyes and neck muscles. It
is present through evolution in the higher mammals and continues through life although the quantity may vary.
Loss and/or disturbance in this stage of sleep are associated with several somatic, psychic, developmental and
other disorders, however, the mechanism of its regulation, function and mode of action(s) were unknown, which
are the focus of Biren Mallick’s study. In brief, his studies may broadly be described under Neuro-anatomical
and neurochemical mechanism of regulation of REM sleep and Functions of REM sleep which have been
discussed below under four heads (A-D).
A) Mechanism of Neural Regulation of Rapid Eye Movement Sleep Generation :
a) Cessation of activity of REM-OFF neurons in the locus coeruleus (LC) is a pre-requisite for REM
sleep generation (reviewed Pal et al., 2005; Pal and Mallick, 2007) :
Before he started independent work at School of Life Sciences, Jawaharlal Nehru University
(SLS/JNU), it was known that there are cholinergic REM-ON and noradrenaline (NA)-ergic REM-OFF neurons
in the brain stem and they are likely to be reciprocally connected for the regulation of REM sleep. Since the
REM-OFF neurons are continuously active all through except during REM sleep, he proposed that cessation of
those neurons may be a pre-requisite for the generation of REM sleep. Therefore, he hypothesized that if those
REM-OFF neurons were continuously kept active (i.e. they were not allowed to cease activity), REM sleep
should not be generated or at least significantly reduced. To prove, under surgical anaesthesia electrodes were
implanted for sleep-waking recording and stimulation of locus coeruleus (LC). After recovery, in freely moving
normally behaving rats it was indeed found that upon continuous activation of the LC neurons by mild, low
frequency electrical stimulation, there was significant reduction in REM sleep, which was followed by a
rebound increase in REM sleep after the stimulation was stopped confirming my hypothesis (Singh and
Mallick, 1996).
b) Mechanism of cessation of REM-OFF neurons in LC :
Until mid 1980s based on isolated independent studies existence of reciprocal relationship (when one
neuron is active the other remains inactive) between REM-OFF and REM-ON neurons was proposed for
effective regulation of REM sleep; however the neurochemical nature of such action was unknown.
i) Simultaneous recording of REM-OFF and REM-ON neurons :
In JNU, Biren Mallick initiated and established the facility to maintain animals higher than rats, the
cats. He then successfully established (technique) recording single neuronal activity in freely moving normally
behaving cats. His are the first publications from this country based on single neuronal activity recorded from
freely moving animals. Unlike earlier isolated studies, by simultaneous recording of a pair of REM-OFF and
21
REM-ON neurons in freely moving cats, his group showed for the first time that those neurons are reciprocally
active in relation to REM sleep and waking (Mallick et al., 1998).
ii) Mechanism of inhibition of REM-OFF neurons for REM sleep regulation :
The REM-OFF neurons must stop, while the REM-ON neurons increase firing during REM sleep;
however, their neuro-chemical nature for inducing such behaviour was unknown. The group led by Biren
Mallick proposed that cholinergic input from REM-ON neurons is likely to excite inhibitory GABA-ergic
neurons which in turn would inhibit the REM-OFF neurons for REM sleep generation.
They carried out studies in surgically prepared chronic freely moving rats having electrodes for
recording sleep-waking patterns and indwelling cannulae to microinject receptor agonist and antagonist into the
LC. They used single and sequential microinjection of chemicals in various combinations; the latter technique
was first used by Mallick (Mallick and Alam, 1992). Their findings confirmed that REM-ON cholinergic
output excites the GABA-ergic neurons which inhibit the REM-OFF neurons inducing REM sleep (Mallick et
al., 2001). Thus, Mallick’s group put forward GABA-interneuron model (Mallick et al., 2001), which revised
the earlier models for REM sleep regulation. This is a significant advancement to our understanding on
neurochemical basis of REM sleep regulation (Fig. 1). Subsequently, combining stimulation of prepossitus
hypoglossi (PrH) and simultaneous blocking GABA action by picrotoxin into the LC, they proposed that REM-
ON cholinergic inputs may also excite PrH GABA-ergic neurons, which may also contribute (in addition to the
GABA-ergic interneurons in the LC) towards inhibition of the REM-OFF neurons for REM sleep regulation
(Kaur et al., 2001).
GABA IN LC FOR REM SLEEP MODULATION
Mallick et al., Neuroscience, 2001; J. Biosci., 2002; Kaur et al., Synapse, 2001
Noradrenergic
REM-OFF (LC)
CholinergicREM ON
GABAergic
Noncholinergic
REM-ON
GABA
ergic
(+)
(+)
(+)(+)
(+)
(+)(-)
(-)
(-)
?
(-)
GABA-ergic
REM-ON (PrH)
(-)
(+)
(+)
?
U
?
Preoptic area
Fig. 1
c) Mechanism of excitation of REM-ON neurons for REM sleep regulation :
Thereafter, they investigated role of NA (possibly from LC REM-OFF neurons) on PPT REM-ON
neurons in the above model (Fig. 1) for REM sleep regulation. Using sequential double microinjection of
adrenergic agonist and antagonist along with GABA-ergic antagonist into the PPT, they confirmed interaction
of adrenergic and GABA-ergic inputs on the PPT REM-ON neurons for the regulation of REM sleep (Pal and
22
Mallick, 2006). Subsequently they found that GABA-terminals from substantia nigra possibly acted pre-
synaptically on the NA-ergic terminals in PPT and modulated NA-release on the REM-ON neurons to regulate
REM sleep (Pal and Mallick, 2009) as summarised in Fig 2.
(-)
(-)
NoradrenergicREM-OFF
Neurons
(+)
<
(-)
(?)[187,194]
[187,194]
(-)
[202]
[202,207]
<
[197,199,201]
(+)
[201]
2G
(-)
GABAergic(PrH)
<(+)
[203]
<
CholinergicREM-ONNeurons
[200,201]
<
Brainstem Sleep Inducing
Area
GABAergic
interneurons
[195]
[95]
G
<Brainstem
WakefulnessInducing
Area
ACh
ACh
GABAergic[PPT Interneurons
/SNrpr] <
2 2 - adrenoceptors CholinoceptorsAChGABAA
receptorG - adrenoceptors
[196]
<
<
SCHEMATIC CONNECTIONS FOR REM SLEEP REGULATION
Pal and Mallick, Neuropharmacology, 2006; IJMR, 2007
Fig. 2
d) Mechanism of action of brainstem Sleep and Waking areas in modulating REM sleep :
REM sleep normally follows deep sleep, it does not follow wakefulness and it may end either into
slow sleep or in waking; although these patterns may not hold in disease e.g. narcolepsy. However, the cellular
mechanism for such expression of REM sleep was lacking. Therefore, Mallick proposed that :
i) possibly wake-inducing area inhibit the REM-ON neurons and excite the REM-OFF neruons;
ii) sleep-area possibly stimulate the REM-ON neurons and inhibit the REM-OFF neurons.
Cats were surgically prepared having implanted electrodes for recording behavioural sleep-waking,
single neuronal activities and for inducing sleep or waking at will by stimulation of deep brain areas. After
recovery, the recordings were carried out in freely moving normally behaving conditions. REM-ON and REM-
OFF neurons were recorded and their responses were studied upon stimulation of physiologically confirmed
deep brainstem areas, the midbrain reticular wakefulness inducing area and caudal brainstem reticular formation
sleep inducing area. It was observed that the wakefulness inducing area excited the REM-OFF neurons and
inhibited the REM-ON neurons (Thankachan et al., 2001) (Fig. 3); while the sleep inducing area largely had
opposite influence (Mallick et al. 2004).
23
RAS
To Spinal cord through
bulbar inhibitory area
for muscle tone regulation
Stimulation
RAS stimulation induced EEG desynchronization
REM OFF
(NE)
(+)
REM ON(ACh)
(-)
(+) (-)
(+)GABA
Brain Stem
(-)
Thankachan et al., Brain Res, Bull, 2001; Mallick et al., J. Biosci., 2002
Fig. 3
Based on these results the following working model has been proposed (Mallick et al. 2004) for the
neural regulation of REM sleep (Fig. 4).
i) During waking, the wake inducing area inhibits sleep neurons and activates LC-NA-ergic REM-OFF
neurons, which inhibits the cholinergic REM-ON neurons;
ii) During sleep, wake neurons are inhibited and hence excitation of REM-OFF neurons are withdrawn;
iii) At a depth of sleep, though the exact cause and mechanism are unknown, the sleep inducing area stimulates
REM-ON neurons;
iv) Activation of REM-ON neurons stimulates GABA-ergic neurons (interneurons in LC as well as neurons in
prepossitus hypoglossi) and REM-OFF neurons cease firing initiating REM sleep;
[2]
[1,2]
[3]
[7,8]
[4]
[4]
[5,7]
[6]MidbrainMedulla
Pons
1. Kaur et al., 1997 5. Pal and Mallick 2004
2. Mallick et al., 2001 6. Mallick et al., 2004
3. Kaur et al., 2001 7. Pal and Mallick 2006
4. Thankachan et al., 2001 8. Rye et al., 1987
PPT
LC
PrH
GABA-ergic interneurons
Excitation
Inhibition
Locus coeruleusLC
Pedunculopontine tegmentumPPT
Midbrain wakefulness inducing area
Prepositus hypoglossusPrH
Caudal brainstem sleep inducing areaCBS
CBS
NEURAL MECHANISM OF REM SLEEP GENERATION
Fig. 4 (Book chapter Mallick et al., 2006)
24
e) Physiological verification of the proposed model :
As mentioned above, GABA inhibits the REM-OFF neurons in the LC for REM sleep generation
(reviewed Pal et al., 2005; Pal and Mallick, 2007). For physiological confirmation, it was proposed that if the
model was correct, then if GABA-blocker was intermittently infused into the LC for prolonged period (several
days), the LC-REM-OFF neurons would not cease activity and the following should happen :
i) there should be significant loss of REM sleep; and
ii) it should induce a condition that is observed after otherwise REM sleep deprivation/loss.
Rats were surgically prepared with electrodes for continuous electrophysiological sleep-waking
recording and with implanted bilateral cannula in the LC for chemical injection. Three types of studies were
conducted which are summarized as follows :
a) If GABA was prevented to act on LC (site of REM-OFF neurons), REM sleep was significantly reduced
and simultaneously brain Na-K ATPase activity increased (Kaur et al., 2004); the increased Na-K
ATPase activity was comparable to that of as was observed after REM sleep loss in the rats (Gulyani
and Mallick, 1993) as will be described later in the function section.
b) Prevention of GABA action in the LC induced thermoregulatory changes as that of otherwise REM
sleep loss (Jaiswal and Mallick, 2009) and the effect was mediated by NA.
c) If LC neurons were activated by stimulating Na-K ATPase by microinjecting anti-ouabain antibodies,
REM sleep was significantly reduced (Jaiswal et al., 2009).
Neural Mechanism of REMS regulation has been recently modelled (Fig. 5) in Prog Neurobiol (Mallick
et al., 2012); it has been mathematically reconstructed as well (Kumar et al., PLoS ONE, 2012).
CO
VER
PA
GE
Fig. 5
25
B) Functional Significance of REM Sleep and its Mechanism of Action :
i) Mallick's hypothesis : “One of the functions of REM Sleep is to Maintain Brain Excitability and
thus REM Sleep Serves House Keeping Function of the Brain”. REM sleep loss has been reported to increase
aggressiveness, irritability, fighting behaviour; it also reduces memory consolidation, brain maturation and so
on. Since Na-K ATPase is a key enzyme to maintain neuronal excitability, it was hypothesized that REM
sleep deprivation must be affecting Na-K ATPase activity in the brain. Indeed it was found that REM sleep
loss increased Na-K ATPase (Gulyani and Mallick, 1993) and chloride ATPase (Mallick and Gulyani, 1993)
activities in the rat brain.
ii) REM Sleep deprivation elevates NA levels in the brain :
Mallick and his group showed that REM sleep loss/deprivation modulated the following factors which
would increase NA level in the brain. (a) The NA-ergic REM-OFF neurons, which normally cease activity
during REM sleep, continue firing during REM sleep loss (Mallick et al., 1990); (b) monoamine oxidase
activity decreased causing reduced breakdown of NA resulting in effective increase of NA at the synapse
(Thakkar and Mallick, 1993); and (c) synthesis of tyrosine hydroxylase increased, causing increased NA
synthesis in NA-ergic neurons (Majumdar and Mallick, 2003). Thus, REM sleep loss is likely to increase NA
levels in the brain.
iii) Mechanism of REM sleep deprivation induced increase in Na-K ATPase activity :
Since NA levels increases in the brain after REM sleep deprivation, it was proposed that the elevated
NA could be the candidate for mediating deprivation induced increased Na-K ATPase activity. Indeed the
same was confirmed by both in vivo as well as in vitro studies (Gulyani and Mallick, 1995). Another possible
action could be that the REM sleep deprivation decreased neuronal membrane fluidity which in turn might
increase the Na-K ATPase activity (Mallick et al., 1995). While investigating the mechanism of action, it was
found that, on one hand, the REM sleep deprivation decreased calcium levels in the synaptosome (Mallick and
Gulyani, 1996), on the other hand, NA removed membrane bound calcium and increased the Na-K ATPase
activity (Adya and Mallick, 1998, Mallick and Adya, 1999). At the molecular level it was found that the NA
acted on α-1A adrenoceptor and intracellularly acted through IP3 mechanism to increase the Na-K ATPase
activity by dephosphorylation of the enzyme (Fig. 6) (Mallick et al., 2000). Further, kinetic study showed that
deprivation altered Km as well as Vmax of the enzyme suggesting that the increase in the enzyme activity was
modulated allosterically as well as by increasing synthesis of the enzyme (transcriptionally) (Adya and Mallick,
2000). Allosteric modulation was shown by the above mentioned in vitro studies, while increased synthesis of
the enzyme after REM sleep loss was shown subsequently (Majumdar et al., 2003).
26
1A
NE
PL
C
IP3 DAG
Blocked by
WB4101
Ca++ + CaM
CALCINEURIN
ACTIVATION
Phospho form
(inactive)
Dephospho
Form
(active)
Blocked
by
CYCL.A
PIP2
Blocked by
W 13
Blocked
by
HEPARIN
Mallick et al., J. Neurochem. 2000
Ca++ INCREASE
??
SIGNAL TRANSDUCTION PATHWAY FOR NA-INDUCED
INCREASED Na-K ATPase ACTIVITY
Cell
membrane
Fig. 6
Mallick’s group’s findings suggested that the calcium ions play a complex role in regulating Na-K
ATPase activity. Their systematic studies revealed that NA on one hand reduces calcium influx by closing L-
type Ca-channels, while on the other hand, releases Na-K ATPase bound calcium, which dephosphorylates and
stimulates Na-K ATPase activity (Fig. 7) (Das et al., 2008).
REM Sleep Deprivation
Na-K-ATPase
Phospho-Form
(Inactive)
Increased Na-K-ATPase Activity
Davis & Vincenzi, 1971
CaM
(Inactive)CaM
(Active)
Calcineurin
(Inactive)
Calcineurin
(Active)Ca2+
Mallick et al., 2000
Reduced LP
Reduced
Ca2+ entry
Mallick & Adya, 1999
L-type Ca2+ Channel
?
Increased NA
Na-K-ATPase
Dephospho-Form
(Active)
Neuronal
MembraneNeuronal
Membrane
Open Closed
?Ca2+
EXTRACELLULAR
INTRACELLULAR
Lu et al., 2002 PLC
Das et al., Neuroscience, 2008
Fig. 7
This part of Mallick’s findings may be summarised as “REM sleep deprivation increases NA in the
brain which acted on alpha1A adrenoceptor, modulates intracellular calcium which increases Na-K ATPase
27
activity due to dephosphorylation resulting in increased neuronal excitability, which ultimately causes REM
sleep deprivation induced disorders” (Fig. 8).
Calcineurin
active
REM Sleep DeprivationN
a-K A
TP
ase
NA
Na-K ATPase
inactive
NA
[198
]
PLC
active
PLC
inactive
Calmodulin
active
Calcineurin
inactive
α1 PIP2
IP3
+ D
AG
[196
]
[196]
Reduced
calcium
influx
Na-K ATPase
active
[193]
[194]
[120
,198
]
Mg++-ATP
X
Red
uced
Lip
id P
erox
idat
ion
NA
(-)
α1
NA
Calmodulin
inactive
Ca-
chan
nel
clos
ed
Ca-channel
open
Bound
Calciu
m
Release
Inactive
Act
ive
Dep
hosp
horylation
NA Noradrenalin Ca++
[140]
[198]EXTRACELLULAR
INTRACELLULAR
ELEVATED
Intracellular Mechanism of Action of NA Stimulating Na-K ATPase
Mallick & Singh,
Sleep Med Rev 2011
Fig. 8
iv) Mechanism of REM sleep loss associated decrease in body temperature :
Preoptic area is known to regulate sleep-wakefulness and body temperature. Mallick’s group first
showed that such regulation can be independent of each other and proposed that one of the functions of sleep is
to maintain the body temperature within physiological limit (Mallick and Alam, 1991; 1993; Alam and
Mallick, 1994). His studies brought out a unique mechanism that NA acting on the medial preoptic area,
regulates sleep, wakefulness and body temperature by acting on α-2, β and α-1 adrenoceptor subtypes,
respectively (Mallick and Alam, 1992); such mechanism is likely to exist for other brain mediated functions.
Subsequently using micro-iontophoresis his group confirmed that the temperature sensitive neurons in the
preoptic area do possess α-1 adrenoceptors (Mallick et al., 2002). They also showed that the action of
cholinergic inputs in the preoptic area was mediated through muscarinic receptors (Mallick and Joseph, 1997)
and unlike the adrenergic inputs, although the cholinergic inputs in the preoptic area may not have dissociated
effects on sleep-waking and body temperature, the cholinergic and adrenergic inputs integrate in the preoptic
area for the regulation of those functions (Mallick and Joseph, 1998). Additionally, very recently it has been
shown that the GABA-ergic neurotransmission in the preoptic area is spontaneously active for modulation of the
hypnogenic functions, including REM sleep, and the action is mediated through GABA-A receptor (Ali et al.,
1999). They identified specific adrenergic and GABA-ergic receptor subtypes on warm and cold
thermosensitive neurons in the preoptic area. Although both the temperature sensitive neurons in the preoptic
area express similar response to adrenergic inputs (Mallick et al., 2002), warm and cold sensitive neurons
express opposite response to GABA (Jha et al., 2001) and to inputs from waking area in the brain stem
(Mallick et al., 2004). The findings led them to propose GABA acts pre-synaptically on the NA-ergic
28
terminals projecting on the warm sensitive neurons but post-synaptically on the cold sensitive neurons (Fig.
9) for finer thermoregulation (Jha and Mallick, 2009).
WSNsCSNs
(+)
(+)
P/Q typeCa++
channel(closed)
N type Ca++
channel(Opened)
GABA-A
Receptor
GABA molecule
(+)
Ca 2+
NE
release
Post synaptic
Adreno-
receptors
(+)
GABA-ergic
Neurons
NE-ergic
Neurons
GABA terminal
NE molecule
Pre-synaptic
NE terminal
(-)
Pre-synaptic NE and GABA terminal
Jha and Mallick, Neuroscience, 2009
Fig. 9
These findings help explaining NA mediated mechanism of thermoregulation during different conscious
states including sleep-waking-REM sleep and REM sleep loss, when the NA level is reported to vary in the
body and the brain (Fig. 10). Also, in practice, these findings from Mallick’s group especially their insight
towards understanding on pre-synaptic modulation of neurotransmitter release for regulation of physiological
parameters has significantly helped treating and ameliorating symptoms in Crisponi syndrome patients
(Herholz et al., 2010).
REM Sleep
DECREASED NE
NE-REM-OFF Neurons
Cease FiringMAO-A
Hyperthermia
NE-REM-OFF Neurons
Continue Firing
(-) (+)
(8,19 20,49)(84)
(140) (62)
(131)
(79)
(103)
Increased TH
(68)
(63)
(113)
(83)
WSN CSN
-1 -1
mPOAH
Hypothermia
(+)
WSN CSN
(79)
(72)
mPOAH
REM Sleep Deprivation
Increased
Food
Intake
Decreased MAO-A
INCREASED NE
(-)
-1 -1
(72) (72)
Fig. 9 (Book chapter Mallick et al., 2005)
Fig.10
v) REM Sleep Prevents Apoptosis :
Since REM sleep deprivation increases Na-K ATPase activity, it was proposed that neuronal
morphology and size are likely to be affected after deprivation and in extreme case neuronal survivability is
likely to be compromised. It was indeed found that REM sleep deprivation altered neuronal morphometry and
the effects were different on cholinergic, adrenergic, GABA-ergic and serotonergic neurons and interestingly
29
the effects were also mediated by NA acting through α1 adrenoceptors (Majumdar and Mallick, 2005; Ranjan
et al., 2010). Further, REM sleep loss increases apoptosis and damages structural proteins in neurons suggesting
prevention of neuronal apoptosis is a potent likely function of REM sleep (Majumdar et al., 2006). Subject to
confirmation, they also proposed that age related neurodegenerative diseases may have a bearing on REM
sleep loss because ageing is associated with REM sleep loss and the effects may primarily be mediated by
elevated NA level in the brain.
vi) Homeostasis maintenance - Role of glia :
As it was confirmed that the NA increases Na-K ATPase activity, which would alter the Na and K ionic
exchanges, it was not clear how the ionic homeostasis would be maintained. In an attempt to solve this riddle,
Mallick’s group then found that NA affects the glial Na-K ATPase activity in a manner opposite to that of the
neuronal Na-K ATPase (Baskey et al., 2009) leading them to propose the model in Fig 11.
REMSD
NEURON GLIAK+ K+
K+
K+
K+
K+
K+
K+ K+ K+
K+
K+ K+ K+
Repolarization Uptake
ReleaseReversal Potential
Na+ Na+ Na+ Na+
Increased
NA
(+) (-)
K+ K+ K+
K+
K+
NEURON GLIAK+ K+
K+
K+
K+
K+
K+ K+
K+ K+
K+
K+ K+ K+
Repolarization Uptake
ReleaseReversal Potential
Na+ Na+
Na+ Na+
K+ K+
NORMAL
K+
K+
K+
membrane
membrane membrane
membrane
E
C
F
E
C
F
I
C
F
I
C
F
Mallick & Singh, Sleep Med Rev 2011
Fig 11
C) Structure of alpha1A adrenoceptor :
REM sleep loss induced effects were mediated by NA acting on α1 adrenoceptors. For better
understanding of the action of NA e.g. for drug development, etc one needed to know the structure of
adrenoceptor. Using in silico homology modelling Mallick’s group modelled the α1 adrenoceptor active site
(Vijayan, et al., RCSB ID : rcsb 035534; PDB ID : code 2F75); further they identified the amino
acid residues most crucial for binding of NA and its agonist/antagonist (Ramachandran et al., 2007).
All the findings mentioned here, behavioural to cellular to molecular levels, have been summarized
in Fig. 12. It shows non-cessation of NA-ergic REM-OFF neurons in LC would reduce REM-sleep and
increase NA in the brain. Alternatively if REM sleep is prevented, NA-ergic REM-OFF neurons continue
firing instead of being silent resulting increased NA or, if NA as such is increased in the brain by any other
30
means, it would prevent REM sleep. Thus, increased NA holds key for inducing and mediating REM sleep
loss and associated symptoms - pathological conditions.
5
1. Thankachan et al, Brain Res. Bull. 2001
2. Mallick et al, J. Neurosci. Res., 2004
3. Pal and Mallick, Neurosci. Lett. 2005
4. Mallick et al, Neuroscience 2001
5. Mallick et al, Brain Res. 1989
6. Singh and Mallick, Neurosci. Res., 1996
7. Kaur et al., Behav. Brain Res. 2004
8. Crochet and Sakai, NeuroReport 1999
9. Schaefer et al, Biochem. Pharm. 1975
10. Mallick et al, Neurosci. Res 1995
11. Gulyani and Mallick, Neuroscience, 1995
12. Mallick et al, J. Neurochem. 2000
13. Mazumdar and Mallick, Neuroscience 2005
14. Henneman, Science 1957
15. Moruzzi, Ergebn der Physiol., 1972
(-)
Norepinephrine
Increase
ALTERED BEHAVIOR - DISEASE
Neuronal
Apoptosis
Na-K ATPase
Transcription
Wake Active Area
Sleep Active
neurons
(-)(-)
(-)
(-)REM OFF
NEURONS
REMSD/Picrotoxin/
Electrical Stimulation
REM Sleep LossContinuous
Firing
Lipid
Peroxidation Change
Na-K ATPase
ActivityNeuron Size
Change
REM ON
NEURONS
(+) (+)
GABA(+)
GABA
Membrane
Fluidity Change
1 12
3
44
10
9
13
11, 12
15
5, 6, 7
8
14
Fig. 12
D) Marker for REM Sleep deprivation :
Although REM sleep serves such important function and its loss affects several systems, there is no
easy biomarker for identification and quantification of REM sleep loss. We have identified a blood protein
(~200 KDa) which decreases after REM sleep deprivation. The protein was purified, sequence analyzed and
identified as alpha1-Inhibitor3, a negative acute phase response protein (US Patent; manuscript under
preparation). This protein has a potential to be exploited as a marker and may be used for treating REM sleep
loss induced effects.
Finally, the work done by the group led by Biren Mallick can be summarized as in Fig 13.
31
REM SLEEP LOSS
REDUCED MAO ACTIVITY
Ca2+-Release from
Membrane/Na-K ATPaseα1-adrenoceptorReduced
LP/Ca2+-influx
Altered Brain Excitability
Increased
Na-K ATPase activity
INCREASED NORADRENALIN
Disease/Altered states
INCREASED TH ACTIVITYNON-CESSATION OF FIRING
OF LC-NA-NEURONS
REMS loss induced alteration in brain excitability
Mallick & Singh,
Sleep Med Rev 2011
Thus, REMS is
HOUSE KEEPER
of the brain
Fig 13