Developmental Age and Biological Sex Influence Muscarinic Receptor Function and Neuron Morphology within Layer VI of the Medial Prefrontal Cortex

Abstract

Abstract Acetylcholine (ACh) neurotransmission within the medial prefrontal cortex (mPFC) plays an important modulatory role to support mPFC-dependent cognitive functions. This role is mediated by ACh activation of its nicotinic (nAChR) and muscarinic (mAChR) classes of receptors, which are both present on mPFC layer VI pyramidal neurons. While the expression and function of nAChRs have been characterized thoroughly for rodent mPFC layer VI neurons during postnatal development, mAChRs have not been characterized in detail. We employed whole-cell electrophysiology with biocytin filling to demonstrate that mAChR function is greater during the juvenile period of development than in adulthood for both sexes. Pharmacological experiments suggest that each of the M1, M2, and M3 mAChR subtypes contributes to ACh responses in these neurons in a sex-dependent manner. Analysis of dendrite morphology identified effects of age more often in males, as the amount of dendrite matter was greatest during the juvenile period. Interestingly, a number of positive correlations were identified between the magnitude of ACh/mAChR responses and dendrite morphology in juvenile mice that were not present in adulthood. To our knowledge, this work describes the first detailed characterization of mAChR function and its correlation with neuron morphology within layer VI of the mPFC.