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.
Highlights
Release of the neurotransmitter acetylcholine (ACh) in the HC is important for learning and memory (Micheau and Marighetto, 2011; Teles-Grilo Ruivo and Mellor, 2013)
Large, globular structures were observed among choline acetyltransferase (ChAT)-tauGFP-positive fibers, suggestive of cholinergic interneurons (Grybko et al, 2011)
To define HC layers and determine the cellular distribution of ChAT-tauGFP interneurons, sections were counterstained with DAPI and Neurotrace 640/660
Summary
Release of the neurotransmitter acetylcholine (ACh) in the HC is important for learning and memory (Micheau and Marighetto, 2011; Teles-Grilo Ruivo and Mellor, 2013). The major source of acetylcholine in the HC is extrinsic and supplied by the medial septum-diagonal band of Broca (MS-DBB) (Dutar et al, 1995). Lack of HC ACh is associated with cognitive deficits that are observed in Alzheimer’s disease (Coyle et al, 1983). In addition to the MS-DBB cholinergic projection, cholinergic interneurons intrinsic to the hippocampus have been found that may comprise an intrinsic source of ACh (Frotscher et al, 1986, 2000; Freund and Buzsáki, 1996; Romo-Parra et al, 2003). Frotscher and colleagues demonstrated that this population does not contain mRNA for Frontiers in Synaptic Neuroscience www.frontiersin.org
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