Muscarinic and Nicotinic Modulation of Neocortical Layer 6A Synaptic Microcircuits is Co-operative and Cell-Specific
- 1. Research Centre Juelich, Institute for Neuroscience and Medicine 10
- 2. Research Centre Juelich, Institute for Neuroscience and Medicine 10; RWTH Aachen University Hospital, Dept for Psychiatry, Psychoherapy and Psychosomatics; JARA-Brain
Description
Acetylcholine (ACh) is known to regulate cortical activity during different behavioral states, e.g. wakefulness and attention. Here we show a differential expression of muscarinic ACh receptors (mAChRs) and nicotinic AChRs (nAChRs) in different layer 6A (L6A) pyramidal cell (PC) types of somatosensory cortex. At low concentrations, ACh induced a persistent hyperpolarization in corticocortical (CC) but a depolarization in corticothalamic (CT) L6A PCs via M4 and M1 mAChRs, respectively. At ~1 mM ACh depolarized exclusively CT PCs via α4β2 subunit-containing nAChRs without affecting CC PCs. Miniature EPSC frequency in CC PCs was decreased by ACh but increased in CT PCs. In synaptic connections with a presynaptic CC PC, glutamate release was suppressed via M4 mAChR activation but enhanced by nAChRs via α4β2 nAChRs when the presynaptic neuron was a CT PC. Thus, in layer 6A the interaction of mAChRs and nAChRs results in an altered excitability and synaptic release, effectively strengthening corticothalamic output while weakening corticocortical synaptic signaling.
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- Preprint: https://www.biorxiv.org/content/biorxiv/early/2019/09/02/701318.full.pdf (URL)