Cerebral Cortex – serie

This volume deals with some of the association areas of the cerebral cortex and with the auditory cortex. In the first chapter, by Deepak Pandya and Edward Yeterian, the general architectural features and connections of cortical associ­ ation areas are considered; as these authors point out, in primates the association areas take up a considerable portion of the total cortical surface. Indeed, it is the development of the association areas that accounts for the greatest differ­ ences between the brains of primate and non primate species, and these areas have long been viewed as crucial in the formation of higher cognitive and be­ havioral functions. In the following chapter, Irving Diamond, David Fitzpatrick, and James Sprague consider the question of whether the functions of the as­ sociation areas depend on projections from the sensory areas of the cortex. They use the visual cortex to examine this question and show that there is a great deal of difference between species in the amount of dependence, the differences being paralleled by variations in the manner in which the geniculate and pulvinar nuclei of the thalamus project to the striate and extra striate cortical areas. One of the more interesting and perhaps least understood of the association areas is the cingulate cortex, discussed by Brent Vogt. Cingulate cortex has been linked with emotion and with affective responses to pain, and in his chapter Vogt gives an account of its cytoarchitecture, connections, and functions.

Volume 5 of Cerebral Cortex completes the sequence of three volumes on the individual functional areas of the cerebral cortex by covering the somatosensory and motor areas. However, the chapters on these areas lead naturally to a series of others on patterns of connectivity in the cortex, intracortical and subcortical, so that the volume as a whole achieves a much broader viewpoint. The individual chapters on the sensory-motor areas reflect the considerable diversity of interest within the field, for each of the authors has given his or her chapter a different emphasis, reflecting in part topical interest and in part the body of data resulting from work in a particular species. In considering the functional organization of the somatosensory cortex, Robert Dykes and Andre Ruest have chosen to concentrate on the nature of the mapping process and its significance. Harold Burton, in his chapter on the somatosensory fields buried in the sylvian fissure, shows how critical is an understanding of this mapping process in the functional subdivision of the cortex. A frequently overlooked subdivision of the cortex, the vestibular region, is given the emphasis it deserves in a chapter by John Fredrickson and Allan Rubin. The further functional subdivisions that occur within the first somatosensory area are given an anatom­ ical basis in the review by Edward Jones of connectivity in the primate sensory­ motor cortex.

The cerebral cortex, especially that part customarily designated "neocortex," is one of the hallmarks of mammalian evolution and reaches its greatest size, relatively speaking, and its widest structural diversity in the human brain. The evolution of this structure, as remarkable for the huge numbers of neurons that it contains as for the range of behaviors that it controls, has been of abiding interest to many generations of neuroscientists. Yet few theories of cortical evo­ lution have been proposed and none has stood the test of time. In particular, no theory has been successful in bridging the evolutionary gap that appears to exist between the pallium of nonmammalian vertebrates and the neocortex of mam­ mals. Undoubtedly this stems in large part from the rapid divergence of non­ mammalian and mammalian forms and the lack of contemporary species whose telencephalic wall can be seen as having transitional characteristics. The mono­ treme cortex, for example, is unquestionably mammalian in organization and that of no living reptile comes close to resembling it. Yet anatomists such as Ramon y Cajal, on examining the finer details of cortical structure, were struck by the similarities in neuronal form, particularly of the pyramidal cells, and their predisposition to laminar alignment shared by representatives of all vertebrate classes.

Volume 10 is a direct continuation and extension of Volume 3 in this series, Visual Cortex. Given the impressive proliferation of papers on visual cortex over the intervening eight years, Volume 10 has specifically targeted visual cortex in primates and, even so, it has not been possible to survey all of the major or relevant developments in this area. Some research areas are experiencing rapid change and can best be treated more comprehensively in a subsequent volume; for example, elaboration of color vision; patterns and subdivisions of functional columns. One major goal of this volume has been to provide an overview of the intrinsic structural and functional aspects of area 17 itself. Considerable pro­ gress has been made since 1985 in unraveling the modular and laminar organi­ zation of area 17; and this aspect is directly addressed in the chapters by Peters, Lund et al., Wong-Riley, and Casagrande and Kaas. A recurring leitmotif here is the evidence for precise and exquisite order in the interlaminar and tangential connectivity of elements. At the same time, however, as detailed by Lund et al. and Casagrande and Kaas, the very richness of the connectivity implies a multi­ plicity of processing routes. This reinforces evidence that parallel pathways may not be strictly segregated. Further connectional complexity is contributed by the various sets of inhibitory neurons, as reviewed by Lund et al. and Jones et al.

The barrel area is a unique specialization of the cerebral cortex, shared by many species of rodents and some marsupials, in which the somatotopic map of the body surface receives direct morphological expression. Here, the homogeneous sheet of layer IV granule cells seen in most mammals is fractured into large archipelagos, each representing one of the larger subdivisions of the contra­ lateral half-body. Within these larger domains are smaller aggregates of granule cells that contain the concentrated terminations of thalamocortical fibers bear­ ing messages emanating from constellations of receptors located in finer subdi­ visions of a body part. These smaller aggregates are particularly well-defined in the representation of the face, where they form a one-to-one representation of the sinus hairs or vibrissae and where they have been given the name barrels. The first inklings of the unique structure of the parietal cortex of rodents came in the study of Droogleever-Fortuyn (1914), who remarked on the pres­ ence in it of clouds of granule cells 0. 5-1 mm in diameter, which he thought were in some way associated with concentrations of nerve fibers. Little attention, however, was paid to his observations. Lorente de N 6 (1922) later observed dense focal concentrations of afferent fiber ramifications in Golgi preparations of the mouse cortex, calling them glomeruli, and these can now be seen as the structures that form the hearts of the barrels and around which the granule cells concentrate.

Over the last twenty-five years, there has been an extensive effort, still growing for that matter, to explore and understand the organization of extrastriate cor­ tex in primates. We now recognize that most of caudal neocortex is visual in some sense and that this large visual region includes many distinct areas. Some of these areas have been well defined, and connections, neural properties, and the functional consequences of deactivations have been studied. More recently, non­ invasive imaging of cortical activity patterns during visual tasks has led to an expanding stream of papers on extrastriate visual cortex of humans, and results have been related to theories of visual cortex organization that have emerged from research on monkeys. Against this backdrop, the time seems ripe for a review of progress and a glance at the future. One caveat important to emphasize at the very onset is that the reader may be puzzled or confused by the use of different terminologies. Individual investi­ gators commonly tend to favor different terminologies, but in general some prove more advantageous than others. As discussed by Rowe and Stone (1977) as well as by others, there is an unfortunate tendency for role-indicating names to lead to fixed ideas about function, in contrast to those that are more neutral and adaptable to new findings.

Thisisthefirstvolumeinthe CerelJral Cortexseriesdevotedtomathematicalmodels ofthecortex. Itwasmotivatedbytherealizationthatcomputationalmodelsof individualneuronsandensemblesofneuronsareincreasinglyusedinresearchon corticalorganizationandfunction. Thisis,inpart,becauseofthenowubiquitous presenceofpowerfulandaffordablecomputers. Suitablemachineswereformerly rareinresearchlaboratoriesandrequiredsubstantialprogrammingexpertisetobe usedinconstructingandusingneuronalmodels. However,computersarenow routinelyusedinallareasofneurobiologyandanumberofsoftwarepackagesallow scientistswithminimalcomputerscienceandmathematicalbackgroundstocon- structseriousneuronalmodels. Asecondfactorleadingtotheproliferationof modelingstudiesisthedevelopmentoftechnologiesthatallowthekindsofdata collectionneededtodeveloprealisticmodelsofcorticalneurons. Characterization ofthekineticsofvoltage-andligand-gatedchannelsandreceptorshadbeenlim- itedtorelativelylargeneurons. However,therapiddevelopmentofsliceprepara- tions,patch-clampmethods,andimagingmethodsbasedonvoltage-sensitivedyes andintracellularcalciumindicatorshasresultedinasignificantdatabaseonthe biophysicalfeaturesofcorticalneurons.Thescopeofmodelingapproachestocorticalneuronsandfunctionsiswide anditseemednecessarytolimitthepurviewofthevolume. Thefocusisonattempts tounderstandthepropertiesofindividualcorticalneuronsandneuronalcircuitry throughmodelsthatincorporatesignificantfeaturesofcellularmorphologyand physiology. Noattemptwasmadetoincludemodelingapproachestounderstanding corticaldevelopmentandplasticity. Thus,workdealingwiththedevelopmentof oculardominancecolumnsandtheorientationselectivityofneuronsinvisualcortex isnotconsidered. Similarly,modelsdealingwiththecellularmechanismsunderlying long-termplasticityandwithapproachestolearningandmemorybasedonmodifica- tionofHebbiansynapsesarenotconsidered. Relativelyabstractattemptstounder- standhigherlevelandcognitiveprocessesbasedonneuralnetsrepresentasecond, majorareaofworkthatisnottreated. Modelsofcognitiveprocessesbasedon dynamicalsystemsmethodsinwhichnoattemptismadetoincludethebiophysical featuresofindividualneuronsarealsonotconsidered. vii viii Thetenmajorchaptersfallintothreegroups. Thefirstgroupdealswith compartmentalmodelsofindividualcorticalneurons.LyleBorg-Grahamprovides PREFACE anintroductiontothemethodsinvolvedinconstructingcompartmentalmodels andthenreviewstheexistingmodelsofhippocampalpyramidalcells. Becauseof theeffectivenessofhippocampalslicepreparations,theseneuronshavewell-ehar- acterizedbiophysicalproperties. Thischapterillustrateshowcompartmentalmod- elscanbeusedtosynthesizeexperimentaldataandprovideanintegrativeviewof thepropertiesofindividualneurons. PaulRhodescontinuesthethemebyfocusing ontheroleofvoltage-gatedchannelslocatedonthedendritesofcorticalneurons. Thisisanareainwhichtechnologicaladvancesinthevisualizationofneuronsin slicepreparationsbasedoninfraredmicroscopyhavegreatlyexpandedtheinfor- mationavailableondendriticfunctioninjustafewyears. Thechapterbothreviews theexperimentaldataonactivedendriticconductancesandemphasizestheirpo- tentialfunctionalroles. Thesecondgroupofchaptersdealwiththegenerationofreceptivefield propertiesofneuronswithinvisualcortex. Theyaddressissuesstemmingfromthe originalattempttounderstandhowthereceptivefieldpropertiesofneuronsincat andmonkeyprimaryvisualcortexaregeneratedbyinteractionsbetweengenicu- lateafferentsandcorticalneurons.ThechapterbyFlorentinWorgotterevaluates modelsthathavebeenusedtoanalyzethegenerationofreceptivefieldproperties. RodneyDouglasandhiscolleaguesaddressaspecificsetofissuesdealingwiththe roleofintracorticalexcitationmediatedbypyramidalcellcollaterals. Animportant featureofthischapterisitsrelationtoattempttoconstructfabricatedcircuitsthat duplicatethefunctionsofcorticalcircuits. ThechapterbyPhilipUlinskifocuseson thegenerationofmotion-selectivepropertiesincorticalneurons. Itseekstoidenti- tycellularmechanismsusedbyneuronsthatrespondpreferentiallytovisualstimuli movingwithparticularspeedsordirections. MatteoCarandiniandhiscolleagues discussthefeatureofcorticalneurons,knownasgaincontrol,thatallowsneurons torespondeffectivelytovisualstimulibypoolinginformationacrosspopulationsof corticalneurons. ThechapterbyHughWilsondealswiththereceptivefieldproper- tiesofextrastriateareasandintroducesnewworkanalyzingface-selectiveneurons. Thefinalsetofchaptersconsidermodelsofensemblesofthalamicandcortical neurons. ThechapterbyWilliamLyttonandElizabethThomasusesthetheoryof dynamicalsystemstoanalyzethetemporalrelationshipsbetweenthalamicand corticalneurons.Animportantfeatureoftheinteractionbetweenthalamusand cortexisthepresenceofoscillationsthatdependinpartuponthevoltage-gated conductancespresentonindividualneuronsandinpartonthestructureofthe overallnetwork. PaulBushcontinuesthisemphasisonoscillationsbydiscussinga modelthatdealswiththegenerationofsynchronizedoscillationsinvisualcortex. Oscillationsofthiskindhaveattractedsubstantialattentioninrecentyearsbecause oftheirpotentialroleincognitiveprocesses. Thelastchapter,byMichaelHasselmo andChristianeLinster,reviewstheirworkonmodelingpiriformcortex,emphasiz- ingtheroleofcholinergicmechanismsinmodulatingtheactivityofcorticalneu- rons. Anattempthasbeenmadethroughouttomakethevolumeaccessibleto readerswithminimalmathematicalbackgrounds. Thevolumethusbeginswitha shorthistoryofmodelsofcorticalneuronsandcircuitrythatintroducestheprinci- palmodelingstyles. ThechaptersbyWorgotterandUlinskicontainmoreextensive ix introductionstosomeofthemodelingmethodsthathavebeenusedtostudyvisual cortex,andthemathematicallychallengedreaderwillfindthatthechapterby PREFACE LyttonandThomascontainsareadableintroductiontotheuseofdynamical systemstheoryinneurobiology. PhilipS. Ulinski EdwardG.Jones Chicago and Davis Contents Chapter 1 ModelingCorticalCircuitry:AHistoryandProspectus PhilipS. Ulinski 1. Introduction "...1 2. LorentedeNothroughDynamicalSystemsModels...2 2. 1. LorentedeNo...2 2. 2. CellAssembliesandNeuralNets...3 2. 3. DynamicSystemsModels...8 3. HodgkinandHuxleythroughNetworkModels...11 3. 1. HodgkinandHuxley...11 3. 2. WilfridRall...11 3. 3. SoftwarePackages...13 3. 4. RealisticModelsofCorticalNetworks...14 4. Prospectus...14 5. References...15 Chapter 2 InterpretationsofDataandMechanismsforHippocampalPyramidal CellModels LyleJ Borg-Graham 1. Introduction...19 1. 1. NeuronModelEvolution-followingElectrophysiology...19 1. 2. NeuronModelEvaluation-followingtheParameters...21 1. 3. WhyHippocampus? 21 1. 4. OrganizationofThisChapter...22 xi xii 2. TheDatabaseforSingle-NeuronModels...23 2. 1. VoltageClampversusCurrentClamp...23 CONTENTS 2. 2. Single-ChannelversusMacroscopicCurrents...24 2. 3. TypeofPreparation...24 2. 4. KineticandPharmacologicalDissection...25 2. 5. TemperatureDependence...26 2. 6. AgeDependence...27 2. 7. HippocampalSubfieldDependence...27 2. 8. DifferencesinFiringPropertiesbetweenSharpversusPatch Recordings...28 2. 9. TheMeasuredVoltage...

This volume is concerned with neurodegenerative disorders and age-related changes in the structure and function of the cerebral cortex, a topic that has attracted increasing interest as longevity and the number of aged individuals in the population increase.

Volume 5 of Cerebral Cortex completes the sequence of three volumes on the individual functional areas of the cerebral cortex by covering the somatosensory and motor areas. However, the chapters on these areas lead naturally to a series of others on patterns of connectivity in the cortex, intracortical and subcortical, so that the volume as a whole achieves a much broader viewpoint. The individual chapters on the sensory-motor areas reflect the considerable diversity of interest within the field, for each of the authors has given his or her chapter a different emphasis, reflecting in part topical interest and in part the body of data resulting from work in a particular species. In considering the functional organization of the somatosensory cortex, Robert Dykes and Andre Ruest have chosen to concentrate on the nature of the mapping process and its significance. Harold Burton, in his chapter on the somatosensory fields buried in the sylvian fissure, shows how critical is an understanding of this mapping process in the functional subdivision of the cortex. A frequently overlooked subdivision of the cortex, the vestibular region, is given the emphasis it deserves in a chapter by John Fredrickson and Allan Rubin. The further functional subdivisions that occur within the first somatosensory area are given an anatom­ ical basis in the review by Edward Jones of connectivity in the primate sensory­ motor cortex.

The cerebral cortex, especially that part customarily designated "neocortex," is one of the hallmarks of mammalian evolution and reaches its greatest size, relatively speaking, and its widest structural diversity in the human brain. The evolution of this structure, as remarkable for the huge numbers of neurons that it contains as for the range of behaviors that it controls, has been of abiding interest to many generations of neuroscientists. Yet few theories of cortical evo­ lution have been proposed and none has stood the test of time. In particular, no theory has been successful in bridging the evolutionary gap that appears to exist between the pallium of non mammalian vertebrates and the neocortex of mam­ mals. Undoubtedly this stems in large part from the rapid divergence of non­ mammalian and mammalian forms and the lack of contemporary species whose telencephalic wall can be seen as having transitional characteristics. The mono­ treme cortex, for example, is unquestionably mammalian in organization and that of no living reptile comes close to resembling it. Yet anatomists such as Ramon y Cajal, on examining the finer details of cortical structure, were struck by the similarities in neuronal form, particularly of the pyramidal cells, and their predisposition to laminar alignment shared by representatives of all vertebrate classes.

This volume of Cerebral Cortex is dedicated to Sir John Eccles, who was an active member of the advisory board for the series until his death in May 1997. His input as to what topics should be covered in future volumes of this series will be sorely missed. The present volume is concerned with neurodegenerative disorders and age­ related changes in the structure and function of the cerebral cortex, a topic that has attracted increasing interest as longevity and the number of aged individuals in the population increase. Although much of the research on the neurodegenerative effects of aging has been centered on Alzheimer's disease, most of the aging popu­ lation will not be afflicted by this disease. They will, however, be affected by the consequences of normal aging, so the first few chapters of this volume are con­ cerned with that topic. Chapter 1, by Marilyn S. Albert and Mark B. Moss, gives an account of the cognitive changes that accompany normal human aging. Chapter 2, by Mark B.

Thisisthefirstvolumeinthe CerelJral Cortexseriesdevotedtomathematicalmodels ofthecortex. Itwasmotivatedbytherealizationthatcomputationalmodelsof individualneuronsandensemblesofneuronsareincreasinglyusedinresearchon corticalorganizationandfunction. Thisis,inpart,becauseofthenowubiquitous presenceofpowerfulandaffordablecomputers. Suitablemachineswereformerly rareinresearchlaboratoriesandrequiredsubstantialprogrammingexpertisetobe usedinconstructingandusingneuronalmodels. However,computersarenow routinelyusedinallareasofneurobiologyandanumberofsoftwarepackagesallow scientistswithminimalcomputerscienceandmathematicalbackgroundstocon- structseriousneuronalmodels. Asecondfactorleadingtotheproliferationof modelingstudiesisthedevelopmentoftechnologiesthatallowthekindsofdata collectionneededtodeveloprealisticmodelsofcorticalneurons. Characterization ofthekineticsofvoltage-andligand-gatedchannelsandreceptorshadbeenlim- itedtorelativelylargeneurons. However,therapiddevelopmentofsliceprepara- tions,patch-clampmethods,andimagingmethodsbasedonvoltage-sensitivedyes andintracellularcalciumindicatorshasresultedinasignificantdatabaseonthe biophysicalfeaturesofcorticalneurons.Thescopeofmodelingapproachestocorticalneuronsandfunctionsiswide anditseemednecessarytolimitthepurviewofthevolume. Thefocusisonattempts tounderstandthepropertiesofindividualcorticalneuronsandneuronalcircuitry throughmodelsthatincorporatesignificantfeaturesofcellularmorphologyand physiology. Noattemptwasmadetoincludemodelingapproachestounderstanding corticaldevelopmentandplasticity. Thus,workdealingwiththedevelopmentof oculardominancecolumnsandtheorientationselectivityofneuronsinvisualcortex isnotconsidered. Similarly,modelsdealingwiththecellularmechanismsunderlying long-termplasticityandwithapproachestolearningandmemorybasedonmodifica- tionofHebbiansynapsesarenotconsidered. Relativelyabstractattemptstounder- standhigherlevelandcognitiveprocessesbasedonneuralnetsrepresentasecond, majorareaofworkthatisnottreated. Modelsofcognitiveprocessesbasedon dynamicalsystemsmethodsinwhichnoattemptismadetoincludethebiophysical featuresofindividualneuronsarealsonotconsidered. vii viii Thetenmajorchaptersfallintothreegroups. Thefirstgroupdealswith compartmentalmodelsofindividualcorticalneurons.LyleBorg-Grahamprovides PREFACE anintroductiontothemethodsinvolvedinconstructingcompartmentalmodels andthenreviewstheexistingmodelsofhippocampalpyramidalcells. Becauseof theeffectivenessofhippocampalslicepreparations,theseneuronshavewell-ehar- acterizedbiophysicalproperties. Thischapterillustrateshowcompartmentalmod- elscanbeusedtosynthesizeexperimentaldataandprovideanintegrativeviewof thepropertiesofindividualneurons. PaulRhodescontinuesthethemebyfocusing ontheroleofvoltage-gatedchannelslocatedonthedendritesofcorticalneurons. Thisisanareainwhichtechnologicaladvancesinthevisualizationofneuronsin slicepreparationsbasedoninfraredmicroscopyhavegreatlyexpandedtheinfor- mationavailableondendriticfunctioninjustafewyears. Thechapterbothreviews theexperimentaldataonactivedendriticconductancesandemphasizestheirpo- tentialfunctionalroles. Thesecondgroupofchaptersdealwiththegenerationofreceptivefield propertiesofneuronswithinvisualcortex. Theyaddressissuesstemmingfromthe originalattempttounderstandhowthereceptivefieldpropertiesofneuronsincat andmonkeyprimaryvisualcortexaregeneratedbyinteractionsbetweengenicu- lateafferentsandcorticalneurons.ThechapterbyFlorentinWorgotterevaluates modelsthathavebeenusedtoanalyzethegenerationofreceptivefieldproperties. RodneyDouglasandhiscolleaguesaddressaspecificsetofissuesdealingwiththe roleofintracorticalexcitationmediatedbypyramidalcellcollaterals. Animportant featureofthischapterisitsrelationtoattempttoconstructfabricatedcircuitsthat duplicatethefunctionsofcorticalcircuits. ThechapterbyPhilipUlinskifocuseson thegenerationofmotion-selectivepropertiesincorticalneurons. Itseekstoidenti- tycellularmechanismsusedbyneuronsthatrespondpreferentiallytovisualstimuli movingwithparticularspeedsordirections. MatteoCarandiniandhiscolleagues discussthefeatureofcorticalneurons,knownasgaincontrol,thatallowsneurons torespondeffectivelytovisualstimulibypoolinginformationacrosspopulationsof corticalneurons. ThechapterbyHughWilsondealswiththereceptivefieldproper- tiesofextrastriateareasandintroducesnewworkanalyzingface-selectiveneurons. Thefinalsetofchaptersconsidermodelsofensemblesofthalamicandcortical neurons. ThechapterbyWilliamLyttonandElizabethThomasusesthetheoryof dynamicalsystemstoanalyzethetemporalrelationshipsbetweenthalamicand corticalneurons.Animportantfeatureoftheinteractionbetweenthalamusand cortexisthepresenceofoscillationsthatdependinpartuponthevoltage-gated conductancespresentonindividualneuronsandinpartonthestructureofthe overallnetwork. PaulBushcontinuesthisemphasisonoscillationsbydiscussinga modelthatdealswiththegenerationofsynchronizedoscillationsinvisualcortex. Oscillationsofthiskindhaveattractedsubstantialattentioninrecentyearsbecause oftheirpotentialroleincognitiveprocesses. Thelastchapter,byMichaelHasselmo andChristianeLinster,reviewstheirworkonmodelingpiriformcortex,emphasiz- ingtheroleofcholinergicmechanismsinmodulatingtheactivityofcorticalneu- rons. Anattempthasbeenmadethroughouttomakethevolumeaccessibleto readerswithminimalmathematicalbackgrounds. Thevolumethusbeginswitha shorthistoryofmodelsofcorticalneuronsandcircuitrythatintroducestheprinci- palmodelingstyles. ThechaptersbyWorgotterandUlinskicontainmoreextensive ix introductionstosomeofthemodelingmethodsthathavebeenusedtostudyvisual cortex,andthemathematicallychallengedreaderwillfindthatthechapterby PREFACE LyttonandThomascontainsareadableintroductiontotheuseofdynamical systemstheoryinneurobiology. PhilipS. Ulinski EdwardG.Jones Chicago and Davis Contents Chapter 1 ModelingCorticalCircuitry:AHistoryandProspectus PhilipS. Ulinski 1. Introduction "...1 2. LorentedeNothroughDynamicalSystemsModels...2 2. 1. LorentedeNo...2 2. 2. CellAssembliesandNeuralNets...3 2. 3. DynamicSystemsModels...8 3. HodgkinandHuxleythroughNetworkModels...11 3. 1. HodgkinandHuxley...11 3. 2. WilfridRall...11 3. 3. SoftwarePackages...13 3. 4. RealisticModelsofCorticalNetworks...14 4. Prospectus...14 5. References...15 Chapter 2 InterpretationsofDataandMechanismsforHippocampalPyramidal CellModels LyleJ Borg-Graham 1. Introduction...19 1. 1. NeuronModelEvolution-followingElectrophysiology...19 1. 2. NeuronModelEvaluation-followingtheParameters...21 1. 3. WhyHippocampus? 21 1. 4. OrganizationofThisChapter...22 xi xii 2. TheDatabaseforSingle-NeuronModels...23 2. 1. VoltageClampversusCurrentClamp...23 CONTENTS 2. 2. Single-ChannelversusMacroscopicCurrents...24 2. 3. TypeofPreparation...24 2. 4. KineticandPharmacologicalDissection...25 2. 5. TemperatureDependence...26 2. 6. AgeDependence...27 2. 7. HippocampalSubfieldDependence...27 2. 8. DifferencesinFiringPropertiesbetweenSharpversusPatch Recordings...28 2. 9. TheMeasuredVoltage...

Volume 2 of Cerebral Cortex continues our policy of dealing with the individual elements of the cerebral cortex before moving on in subsequent volumes to a consideration of the details of the various functional areas. Volume 1 of the treatise dealt with the morphology of cortical neurons, and Volume 2 continues this theme to some extent by including chapters devoted to the morphology of cortical neuroglial cells, of immunocytochemically labeled neurons, and of in­ tracellularly i~ected neurons. However, the major emphasis of this volume and of Volume 3, which will follow it, is on the functional characteristics of cortical neurons and neuroglial cells, particularly those of transmitter and receptor iden­ tity and of electrophysiological uniqueness. Volume 2 emphasizes these char­ acteristics in relation to the intrinsic cortical elements; Volume 3 will continue this and add chapters on the afferent and efferent systems of the cortex. Together, Volumes 2 and 3 will cover all of the transmitters, receptors, and related compounds that have so far been discovered in the cerebral cortex. It is the interrelations among the neuronal elements expressing these materials that determine the functional operations of the cerebral cortex, and the necessity for understanding how the appropriate cooperation between the neuronal ele­ ments is achieved is highlighted by Sir John C. Eccles's introductory chapter on "The Cerebral Neocortex: A Theory of Its Operation.

Volume 6 of Cerebral Cortex is in some respects a continuation of Volume 2, which dealt with the functional aspects of cortical neurons from the physiological and pharmacological points of view. In the current volume, chapters are devoted to the catecholamines, which for a number of reasons were not represented in the earlier volume, and to acetylcholine and the neuropeptides, about which much new information has recently appeared. Volume 6 deals in part with the structure and function of cholinergic and catecholaminergic neuronal systems in the cerebral cortex and with new aspects of the cortical peptidergic neurons, notably the almost universal propensity of the known cortical peptides for being colocalized with classical transmitters and with one another. It thus completes our coverage of the major cortical neuro­ transmitter and neuromodulatory systems. Other chapters in this volume deal with data pertaining to the proportions of different types of cells and synapses in the neocortex and the physiology of the cortical neuroglial cells. These latter are topics that rarely receive separate treatment and the current chapters serve again to continue discussions of subjects that were introduced in Volume 2. The previous volumes have all been devoted to the neocortex but the present one introduces the subject of the archicortex. To this end, separate chapters are devoted to the physiology and anatomy of the hippocampal formation.

The previous volumes in this series have dealt with the mature cerebral cortex. In those volumes many of the structurally and physiologically distinct areas of the cerebral cortex, their connections, the various types of neurons and neuroglial cells they contain, and the functions of those cells have been considered. In the present volume the contributions focus on the development of the neocortex and hippocampus. Chapters in this volume describe how the neurons migrate in the cortex to attain their ultimate positions, and emphasize the role played by the preexisting pallium or primordial plexiform layer of the cerebral vesicle in the development of the cerebral cortex. The primordial plexiform layer becomes split by the invasion of neurons that will form the cortical plate, and mutants in which the neuronal migration is abnormal provide valuable information about the role of the radial glial cells in this migration. It is also made clear that although the mechanics of development in the hippocampus are similar to those in the neocortex, the development of the hippocampus involves some unique features. For example, neuronal proliferation in the dentate gyrus continues well into postnatal life.

This volume of the series on "Cerebral Cortex" deals with a variety of topics that need to be considered in our overall understanding of the functions of the cerebral hemispheres. Chapters in the first part of this volume deal with normal functions that were not covered in earlier volumes, while chapters in the latter part deal with the functioning of the cortex in various altered states. The first chapter is by Eberhard Fetz, Keisuke Toyama, and Wade Smith, and it considers the interactions that can be demonstrated to exist between cortical neurons by using the technique of cross-correlation. The second chapter is by Brent Vogt who examines the connections and functions of layer I of the cerebral cortex, a layer that has been largely ignored in the past, and he proposes that this layer probably plays an important role in learning and memory acquisi­ tion. This is followed by a chapter in which Oswald Steward presents a review of what is currently known about synaptic replacement following denervation of cortical neurons, and especially those in the hippocampus.

Lorente de N 6 (1922) later observed dense focal concentrations of afferent fiber ramifications in Golgi preparations of the mouse cortex, calling them glomeruli, and these can now be seen as the structures that form the hearts of the barrels and around which the granule cells concentrate.

This volume deals with some of the association areas of the cerebral cortex and with the auditory cortex. In the first chapter, by Deepak Pandya and Edward Yeterian, the general architectural features and connections of cortical associ­ ation areas are considered; as these authors point out, in primates the association areas take up a considerable portion of the total cortical surface. Indeed, it is the development of the association areas that accounts for the greatest differ­ ences between the brains of primate and non primate species, and these areas have long been viewed as crucial in the formation of higher cognitive and be­ havioral functions. In the following chapter, Irving Diamond, David Fitzpatrick, and James Sprague consider the question of whether the functions of the as­ sociation areas depend on projections from the sensory areas of the cortex. They use the visual cortex to examine this question and show that there is a great deal of difference between species in the amount of dependence, the differences being paralleled by variations in the manner in which the geniculate and pulvinar nuclei of the thalamus project to the striate and extra striate cortical areas. One of the more interesting and perhaps least understood of the association areas is the cingulate cortex, discussed by Brent Vogt. Cingulate cortex has been linked with emotion and with affective responses to pain, and in his chapter Vogt gives an account of its cytoarchitecture, connections, and functions.

The cerebral cortex, especially that part customarily designated "neocortex," is one of the hallmarks of mammalian evolution and reaches its greatest size, relatively speaking, and its widest structural diversity in the human brain. The evolution of this structure, as remarkable for the huge numbers of neurons that it contains as for the range of behaviors that it controls, has been of abiding interest to many generations of neuroscientists. Yet few theories of cortical evo­ lution have been proposed and none has stood the test of time. In particular, no theory has been successful in bridging the evolutionary gap that appears to exist between the pallium of nonmammalian vertebrates and the neocortex of mam­ mals. Undoubtedly this stems in large part from the rapid divergence of non­ mammalian and mammalian forms and the lack of contemporary species whose telencephalic wall can be seen as having transitional characteristics. The mono­ treme cortex, for example, is unquestionably mammalian in organization and that of no living reptile comes close to resembling it. Yet anatomists such as Ramon y Cajal, on examining the finer details of cortical structure, were struck by the similarities in neuronal form, particularly of the pyramidal cells, and their predisposition to laminar alignment shared by representatives of all vertebrate classes.

Over the last twenty-five years, there has been an extensive effort, still growing for that matter, to explore and understand the organization of extrastriate cor­ tex in primates. We now recognize that most of caudal neocortex is visual in some sense and that this large visual region includes many distinct areas. Some of these areas have been well defined, and connections, neural properties, and the functional consequences of deactivations have been studied. More recently, non­ invasive imaging of cortical activity patterns during visual tasks has led to an expanding stream of papers on extrastriate visual cortex of humans, and results have been related to theories of visual cortex organization that have emerged from research on monkeys. Against this backdrop, the time seems ripe for a review of progress and a glance at the future. One caveat important to emphasize at the very onset is that the reader may be puzzled or confused by the use of different terminologies. Individual investi­ gators commonly tend to favor different terminologies, but in general some prove more advantageous than others. As discussed by Rowe and Stone (1977) as well as by others, there is an unfortunate tendency for role-indicating names to lead to fixed ideas about function, in contrast to those that are more neutral and adaptable to new findings.