The Connected Hippocampus

252 Pages·2015·7.901 MB·English

by  Shane O'Mara, Marian Tsanov (eds.)

Serial Editor
Vincent Walsh
InstituteofCognitiveNeuroscience
UniversityCollegeLondon
17QueenSquare
LondonWC1N3ARUK
Elsevier
Radarweg29,POBox211,1000AEAmsterdam,Netherlands
TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UK
225WymanStreet,Waltham,MA02451,USA
Firstedition2015
#2015ElsevierB.V.Allrightsreserved
Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,
electronicormechanical,includingphotocopying,recording,oranyinformationstorageand
retrievalsystem,withoutpermissioninwritingfromthepublisher.Detailsonhowtoseek
permission,furtherinformationaboutthePublisher’spermissionspoliciesandour
arrangementswithorganizationssuchastheCopyrightClearanceCenterandtheCopyright
LicensingAgency,canbefoundatourwebsite:www.elsevier.com/permissions.
Thisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightbythe
Publisher(otherthanasmaybenotedherein).
Notices
Knowledgeandbestpracticeinthisfieldareconstantlychanging.Asnewresearchand
experiencebroadenourunderstanding,changesinresearchmethods,professionalpractices,or
medicaltreatmentmaybecomenecessary.
Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgein
evaluatingandusinganyinformation,methods,compounds,orexperimentsdescribedherein.
Inusingsuchinformationormethodstheyshouldbemindfuloftheirownsafetyandthesafety
ofothers,includingpartiesforwhomtheyhaveaprofessionalresponsibility.
Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors,
assumeanyliabilityforanyinjuryand/ordamagetopersonsorpropertyasamatterofproducts
liability,negligenceorotherwise,orfromanyuseoroperationofanymethods,products,
instructions,orideascontainedinthematerialherein.
ISBN:978-0-444-63549-5
ISSN:0079-6123
ForinformationonallElsevierpublications
visitourwebsiteatstore.elsevier.com
Contributors
John P.Aggleton
SchoolofPsychology, CardiffUniversity, Cardiff, Wales, UK
Jean-ChristopheCassel
LaboratoiredeNeurosciencesCognitivesetAdaptatives,UMR7364,Universite´
de Strasbourg, CNRS, Faculte´ de Psychologie,Neuropoˆlede Strasbourg—GDR
2905 du CNRS, Strasbourg, France
Kat Christiansen
SchoolofPsychology, CardiffUniversity, Cardiff, Wales, UK
Julie R.Dumont
Department ofPsychologicaland Brain Sciences, DartmouthCollege, Hanover,
NH, USA
Michael E.Hasselmo
DepartmentofPsychologicalandBrainSciences,CenterforMemoryandBrain,
CenterforSystems Neuroscience, GraduateProgram forNeuroscience, Boston
University, Boston, MA, USA
Matthew W. Jones
SchoolofPhysiology and Pharmacology, University ofBristol, University Walk,
Bristol, UK
Laura A.Libby
Center for Neuroscience,University of California,Davis,CA, USA
Sheri J.Y. Mizumori
Psychology Department,University of Washington,Seattle,WA, USA
Andrew J.D. Nelson
SchoolofPsychology, CardiffUniversity, Cardiff, UK
Anne Pereirade Vasconcelos
LaboratoiredeNeurosciencesCognitivesetAdaptatives,UMR7364,Universite´
de Strasbourg, CNRS, Faculte´ de Psychologie,Neuropoˆlede Strasbourg—GDR
2905 du CNRS, Strasbourg, France
Charan Ranganath
CenterforNeuroscience,andDepartmentofPsychology,UniversityofCalifornia,
Davis,CA, USA
MaureenRitchey
Center for Neuroscience,University of California,Davis,CA, USA
Edmund T.Rolls
Oxford Centre for Computational Neuroscience,Oxford,and Department of
ComputerScience, University ofWarwick, Coventry, UK
v
vi Contributors
Jeffrey S.Taube
Department ofPsychologicaland Brain Sciences, DartmouthCollege, Hanover,
NH,USA
ValerieL. Tryon
Psychology Department,University ofWashington, Seattle, WA, USA
MarianTsanov
Trinity College Instituteof Neuroscience, and SchoolofPsychology, Trinity
College Dublin, Dublin, Ireland
Seralynne D.Vann
SchoolofPsychology, Cardiff University, Cardiff, UK
Robert P.Vertes
Center for ComplexSystems and Brain Sciences, Florida Atlantic University,
Boca Raton, FL, USA
EmilieWerlen
SchoolofPhysiology andPharmacology, University of Bristol, University Walk,
Bristol, UK
Preface
The hippocampus is an intriguing and anatomically remarkable structure: it is
possessed ofaremarkable curvilinear appearancein coronal section,and itiseasy
tospotinanatomicalsectionwiththenakedeyeinjustaboutanymammalianspe-
cies.Aspecialandimportantfunctionhasbeenascribedtoitasaresultofthepio-
neering work of John O’Keefe (Nobel Laureate, 2014), who described the
remarkable “place cells,” which fire as a function of the location of the rat in the
environment. Two other important discoveries also give it great importance: long-
termpotentiationandamnesia.Long-termpotentiation,thedemonstrationthatsyn-
apses are plastic, was first described in the hippocampus by Tim Bliss and Terje
Lomo.Thefamousamnesicpatient,HM,hadamore-or-lesscompletesurgicalab-
lationofthehippocampus.Correspondingly,thehippocampushasbeenimplicated
inmanyimportantneurocognitivefunctions,withaparticularlatter-dayemphasison
its role in spatial and cognitive mapping, and in declarative (or explicit) memory.
Asubstantialbodyofdatasuggeststhatthehippocampalformationplaysacritical
role in the biological processes underlying at least some forms of memory. Some-
times, however, it feels when reading the many, many papers published annually
on the hippocampus that it sits apart from the brain, with its functions analyzed in
anarrowhippocampo-centricframework—asifthepurposeoftherestofthebrain
istoservetheinformationprocessingneedsofthehippocampus!Thispointismadea
littlefacetiouslyandexaggeratedly,ofcourse.Nonetheless, wefelttheneedtoas-
suagethesefeelingsbyassemblingthisvolume toencourage researcherstosituate
the hippocampus as part of a network connected to the rest of the brain and not to
consideritinisolation.Wethereforepresentaselectionofchaptersthatconcentrate
onunderstandingthefunctionsofthehippocampusintermsoftheconnectivityofthe
hippocampusitself:inotherwords,intermsofitscorticalandsubcorticalinputsand
outputs. To take just one important illustrative example: the anterior thalamic and
rostral thalamic nuclei are abundantly connected with the hippocampal formation
andhavethecapacitytoprofoundlyshapehippocampalspatialandmnemonicinfor-
mationprocessing,akeypointsometimesbeoverlookedinanalysesfavoringofhip-
pocampallydirectedcorticalprocessing.Wealsoknowthatdamagetotheanterior
thalamus results in episodic memory impairment more-or-less similarly severe as
that resulting from hippocampal lesions; this may be a function of lost thalamo-
hippocampalinformationtransfer.However,thetextbooksandtheprimaryliterature
oftenheavilyemphasizethelessonsfrompatientswithhippocampaldamage,while
neglecting the similarly instructive patients with thalamic damage who also suffer
amnesia.Thecomplexityofthalamicsignalsandtheircontributiontotheencoding
ofexperience-dependentmemorytracesinhippocampalformationneedsfurtherin-
vestigation,assignalprocessinginthehippocampalformationdoesnotalwaysfol-
lowacorticofugalroute,butisalsoaffectedprofoundlybythalamofugalsignals.We
shouldconcludethatmemoryisnotaspecializedpropertyofalimitedsetofcortical
areas; rather, all areas of the cortex as well as several subcortical structures are
xiii
xiv Preface
capableofexperience-dependentchangeoverawiderangeoftimescales.Wethere-
forehopethatwewillcorrectthecommonmisconceptionthatthehippocampusisa
closed system, self-sufficiently responsible for the declarative memory formation.
We here would like to thank all the authors of the chapters presented in this
volume—thereisaconsiderablebodyofworktosavorhereandthepleasantfeeling
of having one’s pet prejudices tested andchanged a little tobe enjoyed.
Shane O’Mara andMarian Tsanov
InstituteofNeuroscience
TrinityCollege, Dublin
ARTICLE IN PRESS
If I had a million neurons:
Potential tests of cortico-
hippocampal theories
Michael E. Hasselmo1
DepartmentofPsychologicalandBrainSciences,CenterforMemoryandBrain,CenterforSystems
Neuroscience,GraduateProgramforNeuroscience,BostonUniversity,Boston,MA,USA
1Correspondingauthor:Tel.:[phone];Fax:[phone],
e-mailaddress:[email protected]
Abstract
Considerableexcitementsurroundsnewinitiativestodeveloptechniquesforsimultaneousre-
cordingoflargepopulationsofneuronsincorticalstructures.Thischapterfocusesonthepo-
tentialvalueoflarge-scalesimultaneousrecordingforadvancingresearchoncurrentissuesin
thefunctionofcorticalcircuits,includingtheinteractionofthehippocampuswithcorticaland
subcorticalstructures.Thereviewdescribesspecificresearchquestionsthatcouldbeanswered
usinglarge-scalepopulationrecording,includingquestionsaboutthecircuitdynamicsunder-
lyingcodingofdimensionsofspaceandtimeforepisodicmemory,theroleofGABAergicand
cholinergicinnervationfromthemedialseptum,thefunctionalroleofspatialrepresentations
codedbygridcells,boundarycells,headdirectioncells,andplacecells,andthefactthatmany
modelsrequirecellscodingmovementdirection.
Keywords
Entorhinal cortex, Stellate cells, Medial septum, Time coding, Spatial coding, Oscillatory
interference,Populationrecording.
1 INTRODUCTION
Thetitleofthischapterhasanumberofinspirations.Thetitlewaspartlyinspiredby
asongentitled“IfIhadamilliondollars”bytheCanadianbandBarenakedLadies,
who humorously sing about the things they would do with a million dollars. This
inspiration explains the title, which is not referring to the author having only a
millionneuronsinhisownbrain,buttotheusefulnessofdatafromamillionindi-
vidualneuronsrecordedsimultaneouslyinabehavinganimal.Thisinspirationalso
explainstheambitiousfocusonamillionneurons.Obviously,researchcanbenefit
tremendously from techniques for recording up to a thousand neurons (Dombeck
et al., 2010; Gee et al., 2014; Ghosh et al., 2011; Heys et al., 2014; Sheffield and
ProgressinBrainResearch,ISSN0079-6123,http://dx.doi.org/10.1016/bs.pbr.2015.03.009 1
©2015ElsevierB.V.Allrightsreserved.
ARTICLE IN PRESS
2 A million neurons
Dombeck, 2014), and further benefits will also arise from recording tens of
thousands of neuronsor hundreds ofthousands of neurons.
The scientific inspiration for the title comes as a response to a surprising com-
mentthatIhaveheardfromotherscientistsovertheyears.Thiscommenttakesdif-
ferent forms, but the common gist is that recordings of thousands or millions of
neuronswouldnotbeanymoreusefulthandatafromcurrenttechnology.Ifindthis
commentsurprisingbecauseitseems obvioushowexpandingthenumbers ofneu-
ronswouldbeuseful.ButIhaveheardthecommentmultipletimes,evenfromre-
searcherswhowereinstrumentalindevelopingtechniquesforthecurrentstateofthe
artformultiplesingle-unitrecordinginbehavinganimals.SoIwanttotaketheop-
portunity toanswer the question inthe context of myown area of research.
ThischapterisalsoinspiredbytheannouncementofthefederalBRAINinitiative
(BrainResearchthroughAdvancingInnovativeNeurotechnology).Onecomponent
of this initiative proposes support for recording of activity in large populations of
neurons,showingthatmanyscientistsrecognizetheimportanceofthistypeofdata.
ButIthinkthefieldcanbenefitfromexplicitexamplesofquestionsthatcanbean-
sweredifwehadlargepopulationsofneuronsinawell-structureddatasetobtained
fromanawake,behavingratwithwell-describedbehavior.Answeringthisquestion
notonlysupportstheideaoffundinginnovativeneurotechnologybutalsoprovidesa
framework for presenting someof the interestingcurrent questionsinthe field.
As long as I am moving beyond current technology in terms of the number of
recorded neurons, Iwillalso assume additional highly desirable features about the
data.Iwillassumethatthespikingactivityofneuronscanbeobservedatahightem-
poralresolution,suchasthatobtainedwithmultiplesingle-unitrecording.Thiscon-
trastswiththeslowertimecourseofactivationdataobtainedfromcurrenttechniques
for calcium imaging in large populations of neurons. I will assume the data are
recordedsimultaneouslyoveratleast10mininanawake,behavingratactivelymov-
ingarounditsenvironment.Iwillassumethedataincludetrackingtheheaddirection
andmovementdirectionofthebehavingratinspaceandtime.Iwillassumethatwe
canrecordinmultipledifferentanatomicalregions,and,insomecases,thatwecan
identifytheindividualmolecularidentityoftheneuronsinthepopulation.Iwillnot
initiallymakeanyassumptionsaboutknowledgeoftheconnectivityoftheneurons,
thoughconnectomedatawouldbeusefulwhencoupledwithdataonphysiologyand
molecular identity ofneurons andthe behaviorof the animal.
2 CORTICAL CODING OF SPACE
IfIhaddatafromamillionneurons,onetopprioritywouldbetoanalyzehowgrid
cellsandplacecellsaregenerated.Fundamentalquestionsaboutthenatureofspatial
representations in the cortex would be answered through an understanding of the
mechanismsofgenerationofthespatialfiringpatternsofgridcells.Extensivedata
frommultipleinteractingbrainregionsshouldbeabletoelucidatethemechanismof
ARTICLE IN PRESS
2 Cortical coding of space 3
generation of grid cells, and I think it is useful to consider the steps that could be
taken with such extensive data. The following sections focus on different aspects
ofthisfundamentalquestion,includingthepossibleratecodingofmovementdirec-
tion,thepossiblephasecodingofmovementdirectionandspeed,andthecodingof
sensorycues andboundaries.
TheNobelprizeinphysiologyormedicinein2014acknowledgedtheimportance
ofgridcellsandplacecellsbyrecognizingO’Keefeforthediscoveryofplacecells
(O’Keefe, 1976; O’Keefe and Dostrovsky,1971) andMay-Britt andMoserfor the
discovery of grid cells (Fyhn et al., 2004; Hafting et al., 2005; Moser and Moser,
2008). Initially, grid cells were proposed as a mechanism for driving place cells
(McNaughtonetal.,2006;Solstadetal.,2006),butrecentdatashowinglossofgrid
cellswithinactivationofthehippocampussuggestthatplacecellsmightbedriving
gridcells(Bonnevieetal.,2013).Ineithercase,understandingthegenerationofone
of these phenomena is important tounderstanding the other.
The highly regular pattern of grid cell firing gives a sense that they can be
accountedforbyeleganttheoreticalprinciples,andnumerouspublishedmodelsad-
dressthe mechanism ofgrid cell generation. Grid cell modelscan be grouped into
categoriesbasedonsomeoftheircomponentfeatures.Onecategoryofmodelsuses
attractordynamicstogeneratethecharacteristicfiringpatternofgridcells(Bonnevie
etal.,2013;BurakandFiete,2009;BushandBurgess,2014;Coueyetal.,2013;Fuhs
andTouretzky,2006;Guanellaetal.,2007;McNaughtonetal.,2006).Mostofthe
attractormodelsusecircularlysymmetricinhibitoryconnectivitywithinalargepop-
ulationofgridcellstogeneratecompetitionbetweengridcellscodingnearbyloca-
tions.Thisresultsinapatternofneuralactivityacrossthepopulationthatmatches
thecharacteristichexagonalarrayofgridcellfiringfields(alsodescribedasfalling
ontheverticesoftightlypackedequilateraltriangles).Large-scalerecordingofcells
particularly during first entry to a familiar environment would allow testing of
whetherthe population dynamicsappeartosettleinto anattractor state orwhether
individualneuronsindependentlycodelocation.Asnotedbythemodels,theshared
orientation and spacing of the firing fields of grid cells within individual modules
(Barry et al.,2007;Stensola et al.,2012) andthe sharedshifts offiringfields with
environmentalmanipulations(Barryetal.,2007;Stensolaetal.,2012;Yoonetal.,
2013) already supportthe existence ofattractordynamics.
However,generatingagrid-likepatternacrossapopulationisnotsufficientfor
modelingindividualgridcells.Replicatingthechangesinfiringofanindividualgrid
cellovertimerequiresthatthegrid-likepatterninthepopulationneedstobeshifted
inproportiontothebehavioralmovementoftheanimal,thatis,inproportiontoits
runningvelocity.Togeneratethismovement,mostattractormodelsofgridcellsex-
plicitlycitearoleforexperimentaldataonconjunctivegrid-by-head-directioncells
(Sargolini et al., 2006). In attractor models of grid cells (Burak and Fiete, 2009;
Couey et al., 2013; McNaughton et al., 2006), these grid-by-head-direction cells
areproposedtodriveadjacentneuronswithinthepopulationbasedonthemovement
of the animal. However, there is a fundamental problem in using grid-by-head-
direction cells to represent the movement direction of an animal, as described in