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Distinct Nicotinic Responses Map onto Electrophysiologically‐ and Morphologically‐Distinct Pyramidal Neurons Within Layer 5 of The Mouse Prefrontal Cortex
Author(s) -
Patel Ashutosh,
Nguyen Anthony,
Paletta Pietro,
Choleris Elena,
Bailey Craig
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.01737
Subject(s) - neuroscience , soma , neuron , nicotinic acetylcholine receptor , neurotransmission , nicotinic agonist , bursting , excitatory postsynaptic potential , inhibitory postsynaptic potential , prefrontal cortex , pyramidal cell , dendrite (mathematics) , apical dendrite , postsynaptic potential , electrophysiology , biology , chemistry , receptor , hippocampal formation , biochemistry , cognition , geometry , mathematics
Neurotransmission mediated by acetylcholine at its nicotinic receptors (nAChRs) within the medial prefrontal cortex (mPFC) is critical for higher‐order cognitive tasks. Pyramidal neurons within layer 5 of the mPFC express nAChRs and form the primary signalling outputs from this brain region. These neurons may be categorized as either regular‐firing or initial burst‐firing, based on threshold responses to positive current injection. The objective of this study was to use whole‐cell electrophysiology and biocytin neuron labelling in young postnatal mice (age 15‐20 days) of both sexes to characterize the morphology and nAChR function within each of these neuron categories. When comparing the neuron categories, we first determined that regular‐firing neurons have a greater membrane resistance and spike adaptation ratio, and a lower magnitude post‐firing hyperpolarization. Regular‐firing neurons also exhibited a lower frequency of spontaneous excitatory postsynaptic potentials. Detailed morphological analysis determined that regular‐firing neurons have more apical dendrite matter distal to the soma and more basal dendrite matter proximal to the soma. Pharmacological experiments using receptor‐selective antagonists revealed that nicotinic responses are mediated by distinct nAChR isoforms that are expressed selectively on each of the two pyramidal neuron categories. Specifically, these experiments demonstrate that heteromeric α4β2* nAChRs are present on regular‐firing pyramidal neurons and homomeric α7 nAChRs are present on burst‐firing pyramidal neurons. Ongoing experiments aim to determine the projection targets for each type of pyramidal neuron within each sex. These novel findings suggest a detailed receptor‐based mechanism by which acetylcholine neurotransmission is regulated within output neurons of mPFC layer 5, which may impact the development of cognitive circuits involving this brain region.

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