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Cholinergic afferent stimulation induces axonal function plasticity in adult hippocampal granule cells.

Martinello, K; Huang, Z; Lujan, R; Tran, B; Watanabe, M; Cooper, EC; Brown, DA; (2015) Cholinergic afferent stimulation induces axonal function plasticity in adult hippocampal granule cells. Neuron , 85 (2) 346 - 363. 10.1016/j.neuron.2014.12.030. Green open access

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Abstract

Acetylcholine critically influences hippocampal-dependent learning. Cholinergic fibers innervate hippocampal neuron axons, dendrites, and somata. The effects of acetylcholine on axonal information processing, though, remain unknown. By stimulating cholinergic fibers and making electrophysiological recordings from hippocampal dentate gyrus granule cells, we show that synaptically released acetylcholine preferentially lowered the action potential threshold, enhancing intrinsic excitability and synaptic potential-spike coupling. These effects persisted for at least 30 min after the stimulation paradigm and were due to muscarinic receptor activation. This caused sustained elevation of axonal intracellular Ca(2+) via T-type Ca(2+) channels, as indicated by two-photon imaging. The enhanced Ca(2+) levels inhibited an axonal KV7/M current, decreasing the spike threshold. In support, immunohistochemistry revealed muscarinic M1 receptor, CaV3.2, and KV7.2/7.3 subunit localization in granule cell axons. Since alterations in axonal signaling affect neuronal firing patterns and neurotransmitter release, this is an unreported cellular mechanism by which acetylcholine might, at least partly, enhance cognitive processing.

Type: Article
Title: Cholinergic afferent stimulation induces axonal function plasticity in adult hippocampal granule cells.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuron.2014.12.030
Publisher version: http://dx.doi.org/10.1016/j.neuron.2014.12.030
Language: English
Additional information: This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Keywords: Acetylcholine, Action Potentials, Animals, Axons, Calcium, Calcium Channels, T-Type, Cholinergic Fibers, Dentate Gyrus, Hippocampus, KCNQ2 Potassium Channel, KCNQ3 Potassium Channel, Mice, Mossy Fibers, Hippocampal, Neuronal Plasticity, Neurons, Neurons, Afferent, Potassium, Receptor, Muscarinic M1, Receptors, Muscarinic, Synaptic Potentials, Synaptic Transmission
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/1461101
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