Pyramidal neuron synapses in M2 exhibit properties intermediate between prefrontal cortex and M1 synapses

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Abstract

Motor planning and control is executed by different motor areas within the neocortex. Despite their distinct functions these areas are built by the same archetypes of neurons as the rest of the cortex, with the pyramidal neurons (PNs) as their principal building blocks. Recent results suggest that the synapses of the PNs are modeled and adapted to their required functions in an area specific manner. PN synapses in a cortical area engaged in higher order functions, the prefrontal cortex (PFC), were found to operate with loose microdomain calcium-influx-to-release coupling and showed short-term facilitation, whereas synapses processing sensory information in a lower order cortical area, the primary somatosensory cortex (S1), featured tight nanodomain coupling and showed short-term depression. In the present study, we asked for the functional coupling configuration of an intermediate processing area. We focused on PN synapses in the premotor cortex M2 and compared their properties to those of PN synapses in the primary motor cortex M1. In both areas we found tight nanodomain coupling and high release probability, but a significant difference in short-term plasticity. Synapses in M1 showed paired-pulse depression similar to S1. In contrast, synapses in M2 exhibited paired-pulse facilitation. Our data suggest that this facilitation results from an accelerated recruitment of synaptic vesicles to the readily releasable pool from an enlarged replenishment pool. Thus, PN synapses in M2 appear to have properties intermediate between those in PFC and M1.

Significance Statement

Neocortical areas perform diverse computations despite being composed of the same principal neuronal cell types. How synaptic properties are adapted to these functional demands remains poorly understood. We show that L2/3–L5 pyramidal neuron synapses in the secondary motor cortex (M2) combine features of the primary motor cortex (M1), including tight nanodomain Ca²⁺-influx-to-release coupling and high release probability, with paired-pulse facilitation, previously associated with higher-order cortical areas such as the prefrontal cortex (PFC). Our data suggest that this facilitation is mediated by an enlarged replenishment pool and accelerated vesicle recruitment rather than differences in coupling architecture, highlighting vesicle pool organization as an additional mechanism of area-specific synaptic specialization. Thus, L2/3–L5 pyramidal neuron synapses in M2 exhibit intermediate properties between M1 and PFC.

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