Prefrontal layer V pyramidal neurons comprise multiple subtypes with distinct nicotinic responses and projection targets

The neurotransmitter acetylcholine supports goal-directed cognitive functions via activation of its nicotinic and muscarinic classes of receptors within the prefrontal cortex. These receptors are expressed on pyramidal neurons located within layer V of the prefrontal cortex, which integrate afferent signals and contribute toward cognitive circuits via efferent projections to cortical and subcortical targets. Using whole-cell electrophysiology, retrograde labelling, and neuron reconstruction in the juvenile mouse prefrontal cortex, we identified three unique isoform-specific nicotinic receptor responses that are present in distinct subtypes of layer V pyramidal neurons. Broadly, we observed 7 or 7/{beta}2* nicotinic responses in burst-firing neurons that project to the contralateral cortex or nucleus accumbens, respectively, and {beta}2* nicotinic responses in regular-firing neurons that project to the ventromedial thalamus. These findings provide insight into a receptor isoform-specific mechanism by which nicotinic acetylcholine neurotransmission may support cognitive functions via modulation of distinct efferent projections from this brain region.