ComplementaryRolesofCholecystokinin-andParvalbumin- ExpressingGABAergicNeuronsinHippocampalNetwork Oscillations

In the hippocampal CA1 area, a relatively homogenous population of pyramidal cells is accompanied by a diversity of GABAergic interneurons. Previously, we found that parvalbumin-expressing basket, axo-axonic, bistratified, and oriens-lacunosum moleculare cells,innervatingdifferentdomainsofpyramidalcells,havedistinctfiringpatternsduringnetworkoscillationsinvivo.Asecondfamily of interneurons, expressing cholecystokinin but not parvalbumin, is known to target the same domains of pyramidal cells as do the parvalbumincells.TotestthetemporalactivityoftheseindependentandparallelGABAergicinputs,werecordedtheprecisespiketiming ofidentifiedcholecystokinininterneuronsduringhippocampalnetworkoscillationsinanesthetizedratsanddeterminedtheirmolecular expressionprofilesandsynaptictargets.Thecellswerecannabinoidreceptortype1immunopositive.Contrarytothestereotypedfiring ofparvalbumininterneurons,cholecystokinin-expressingbasketanddendrite-innervatingcellsdischarge,onaverage,with1.72.0Hz duringhigh-frequencyrippleoscillationsinanepisode-dependentmanner.Duringthetaoscillations,cholecystokinin-expressinginterneuronsfirewith8.83.3Hzatacharacteristictimeontheascendingphaseofthetawaves(15581°),whenplacecellsstartfiringin freelymovinganimals.Thefiringpatternsofsomeinterneuronsrecordedindrug-freebehavingratsweresimilartocholecystokinincells in anesthetized animals. Our results demonstrate that cholecystokinin- and parvalbumin-expressing interneurons make different contributions to network oscillations and play distinct roles in different brain states. We suggest that the specific spike timing of cholecystokinin interneurons and their sensitivity to endocannabinoids might contribute to differentiate subgroups of pyramidal cells forming neuronalassemblies,whereasparvalbumininterneuronscontributetosynchronizingtheentirenetwork.