Patel Ashutosh V, Nguyen Anthony, Geremia Ashley A, Zeng Donia, Paletta Pietro, Choleris Elena, Bailey Craig D C
Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada.
Department of Psychology, University of Toronto Scarborough, Toronto, ON, Canada.
Sci Rep. 2025 Jul 11;15(1):25025. doi: 10.1038/s41598-025-10465-5.
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.
神经递质乙酰胆碱通过激活前额叶皮质内的烟碱型和毒蕈碱型受体来支持目标导向的认知功能。这些受体在前额叶皮质第V层的锥体神经元上表达，该层整合传入信号，并通过向皮质和皮质下靶点的传出投射对认知回路做出贡献。利用幼年小鼠前额叶皮质的全细胞膜片钳电生理学、逆行标记和神经元重建技术，我们在第V层锥体神经元的不同亚型中鉴定出三种独特的烟碱型受体反应。大致而言，我们观察到由以下受体介导的反应：（i）投射到对侧皮质的爆发式放电神经元中的突触后α7烟碱型受体；（ii）投射到伏隔核的爆发式放电神经元中的突触后α7和突触前β2烟碱型受体的组合；（iii）投射到腹内侧丘脑的规则放电神经元中的突触后β2烟碱型受体。这些发现为一种机制提供了见解，即烟碱型乙酰胆碱神经传递可能通过在该脑区不同传出投射中发现的独特受体亚型反应来支持认知功能。
