title: Hippocampal "cholinergic interneurons" visualized with the choline acetyltransferase promoter: anatomical distribution, intrinsic membrane properties, neurochemical characteristics, and capacity for cholinergic modulation.
abstract: Release of acetylcholine (ACh) in the hippocampus (HC) occurs during exploration, arousal, and learning. Although the medial septum-diagonal band of Broca (MS-DBB) is the major extrinsic source of cholinergic input to the HC, cholinergic neurons intrinsic to the HC also exist but remain poorly understood. Here, ChAT-tauGFP and ChAT-CRE/Rosa26YFP (ChAT-Rosa) mice were examined in HC. The HC of ChAT-tauGFP mice was densely innervated with GFP-positive axons, often accompanied by large GFP-positive structures, some of which were Neurotrace/DAPI-negative and likely represent large axon terminals. In the HC of ChAT-Rosa mice, ChAT-YFP cells were Neurotrace-positive and more abundant in CA3 and dentate gyrus than CA1 with partial overlap with calretinin/VIP. Moreover, an anti-ChAT antibody consistently showed ChAT immunoreactivity in ChAT-YFP cells from MS-DBB but rarely from HC. Furthermore, ChAT-YFP cells from CA1 stratum radiatum/stratum lacunosum moleculare (SR/SLM) exhibited a stuttering firing phenotype but a delayed firing phenotype in stratum pyramidale (SP) of CA3. Input resistance and capacitance were also different between CA1 SR/LM and CA3 SP ChAT-YFP cells. Bath application of ACh increased firing frequency in all ChAT-YFP cells; however, cholinergic modulation was larger in CA1 SR/SLM than CA3 SP ChAT-YFP cells. Finally, CA3 SP ChAT-YFP cells exhibited a wider AP half-width and weaker cholinergic modulation than YFP-negative CA3 pyramidal cells. Consistent with CRE expression in a subpopulation of principal cells, optogenetic stimulation evoked glutamatergic postsynaptic currents in CA1 SR/SLM interneurons. In conclusion, the presence of fluorescently labeled hippocampal cells common to both ChAT-tauGFP and ChAT-Rosa mice are in good agreement with previous reports on the existence of cholinergic interneurons, but both transgenic mouse lines exhibited unexpected anatomical features that departed considerably from earlier observations.
authors: COBRE Center for Structural and Functional Neuroscience, The University of Montana Missoula, MT, USA ; Department of Biomedical and Pharmaceutical Sciences, The University of Montana Missoula, MT, USA.
authors: Feng
authors: F
authors: Yi
authors: COBRE Center for Structural and Functional Neuroscience, The University of Montana Missoula, MT, USA ; Department of Biomedical and Pharmaceutical Sciences, The University of Montana Missoula, MT, USA ; Davidson's Honors College, The University of Montana Missoula, MT, USA.
authors: Elizabeth
authors: E
authors: Catudio-Garrett
authors: Department of Experimental Zoology and Neurobiology, University of Pécs Pécs, Hungary ; János Szentágothai Research Center Pécs, Hungary.
authors: Robert
authors: R
authors: Gábriel
authors: Department of Experimental Zoology and Neurobiology, University of Pécs Pécs, Hungary ; Department of Sport Biology, University of Pécs Pécs, Hungary.
authors: Marta
authors: M
authors: Wilhelm
authors: Laboratory of Molecular Biology and Genetics, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary.
authors: Ferenc
authors: F
authors: Erdelyi
authors: Laboratory of Molecular Biology and Genetics, Institute of Experimental Medicine, Hungarian Academy of Sciences Budapest, Hungary.
authors: Gabor
authors: G
authors: Szabo
authors: Department of Bioengineering, Stanford University Stanford, CA, USA.
authors: Karl
authors: K
authors: Deisseroth
authors: COBRE Center for Structural and Functional Neuroscience, The University of Montana Missoula, MT, USA ; Department of Biomedical and Pharmaceutical Sciences, The University of Montana Missoula, MT, USA.
authors: Josh
authors: J
authors: Lawrence
keywords: cholinergic modulation; glutamate transmission; hippocampus; optogenetics; transgenic mice