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M3 MuscarinicAcetylcholineReceptor ExpressionConfers DifferentialCholinergicModulation toNeurochemicallyDistinct HippocampalBasket Cell Subtypes Christian A. Cea-Del RioJ. Josh LawrenceLudovic Tricoire2010 год

M3 Muscarinic Acetylcholine Receptor Expression Confers Differential Cholinergic Modulation to Neurochemically Distinct Hippocampal Basket Cell Subtypes
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Аннотация: Cholinergic neuromodulation of hippocampal circuitry promotes network oscillations and facilitates learning and memory through cellular actions on both excitatory and inhibitory circuits. Despite widespread recognition that neurochemical content discriminates between functionally distinct interneuron populations, there has been no systematic examination of whether neurochemically distinct interneuron classes undergo differential cholinergic neuromodulation in the hippocampus. Using GFP transgenic mice that enable the visualization of perisomatically targeting parvalbumin-positive (PV+) or cholecystokinin-positive (CCK+) basket cells (BCs), we tested the hypothesis that neurochemically distinct interneuron populations are differentially engaged by muscarinic acetylcholine receptor (mAChR) activation. Cholinergic fiber activation revealed that CCK BCs were more sensitive to synaptic release of ACh than PV BCs. In response to depolarizing current steps, mAChR activation of PV BCs and CCK BCs also elicited distinct cholinergic response profiles, differing in mAChR-induced changes in action potential (AP) waveform, firing frequency, and intrinsic excitability. In contrast to PV BCs, CCK BCs exhibited a mAChR-induced afterdepolarization (mADP) that was frequency and activity-dependent. Pharmacological, molecular, and loss-of-function data converged on the presence of M3 mAChRs in distinguishing CCK BCs from PV BCs. Firing frequency of CCK BCs was controlled through M3 mAChRs but PV BC excitability was altered solely through M1 mAChRs. Finally, upon mAChR activation, glutamatergic transmission enhanced cellular excitability preferentially in CCK BCs but not in PV BCs. Our findings demonstrate that cell type-specific cholinergic specializations are present on neurochemically distinct interneuron subtypes in the hippocampus, revealing an organizing principle that cholinergic neuromodulation depends critically on neurochemical identity.
Год издания: 2010
Авторы: Christian A. Cea-Del Rio, J. Josh Lawrence, Ludovic Tricoire, Ferenc Erdélyi, Gábor Szabó, Chris J. McBain
Издательство: Society for Neuroscience
Источник: Journal of Neuroscience
Ключевые слова: Neuroscience and Neuropharmacology Research, Receptor Mechanisms and Signaling, Nicotinic Acetylcholine Receptors Study
Другие ссылки: Journal of Neuroscience (PDF)
Journal of Neuroscience (HTML)
PubMed Central (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed (HTML)