Cholinergic modulation of excitatory synapses of the ACC and LPFC
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Acetylcholine modulates neuronal activity in the brain with different responses in activity depending on the region of the brain. Our study was focused on the cholinergic modulation of excitatory synaptic transmission in the monkey anterior cingulate cortex (ACC) and lateral prefrontal cortex (LPFC), with specific focus on the effects of carbachol, a cholinergic agonist, on spontaneous excitatory postsynaptic currents (sEPSCs) and on the expression the muscarinic cholinergic type II (M2) receptor in these regions. We used electrophysiology to analyze the effects of carbachol on sEPSC of layer 3 (LIII) pyramidal neurons from each area. We used confocal microscopy to study the M2 colocalization with axon terminals labeled with vesicular glutamate transporter 1 (VGLUT1) in the ACC and LPFC, and the colocalization of M2 with specific axon terminals from the amygdala labeled with tracer and terminating in the ACC. Results from the electrophysiological experiments showed that both the ACC and LPFC L3 neurons responded to carbachol by decreasing the frequency of sEPSCs. Cells from the LPFC showed a decrease in sEPSC frequency after 4 minutes in carbachol, an earlier timepoint than ACC neurons, which showed a decrease in sEPSCs frequency after 6 minutes in carbachol. In the confocal studies, M2 expression and colocalization with VGLUT1 terminals in the ACC and LPFC were observed. However, we observed a greater total area of M2 expression in the ACC versus the LPFC in layer 1. We found minimal colocalization of the M2 receptor with axon terminals from the amygdala in the ACC. Together, our data show that acetylcholine has distinct interactions with neurons and pathways in ACC and LPFC, which may be related to the distinct function of the two areas in cognition, learning and memory.