Unique nicotinic responses are present in distinct subtypes of mouse medial prefrontal layer V pyramidal neurons.

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 nicotinic receptor responses that are present in distinct subtypes of layer V pyramidal neurons. Broadly, we observed responses mediated by (i) postsynaptic α7 nicotinic receptors in burst-firing neurons that project to the contralateral cortex, (ii) a combination of postsynaptic α7 and presynaptic β2* nicotinic receptors in burst-firing neurons that project to the nucleus accumbens, and (iii) postsynaptic β2* nicotinic receptors in regular-firing neurons that project to the ventromedial thalamus. These findings provide insight into a mechanism by which nicotinic acetylcholine neurotransmission may support cognitive functions via the unique receptor isoform responses found in distinct efferent projections from this brain region.