Approaching behavior and its synaptic and transcriptomic signatures in medial prefrontal cortex pyramidal neurons: the involvement of excitatory neurotransmission and immune system

Approaching (AP) and avoiding (AV) tendencies are basic behavioral aptitudes in responding to rewarding and aversive stimuli, and their balancing (BA) tendency is critical for successful adaptation to the environment. The AP tendency is associated to novelty seeking and it has important evolutionary value in the identification of new sources of reward. However, the AP tendency exposes individuals to potential risks, increasing the predisposition to externalizing behaviors, such as attention deficit and hyperactivity disorder, addiction, and eating disorders. In this framework, even if the medial prefrontal cortex (mPFC) is a crucial hub that supports AP behavior by sustaining attention towards relevant and novel stimuli, its specific synaptic and transcriptomic signatures have not yet been identified. In this research, we used an experimental model of individual differences permitting the selection of a subpopulation of mice that spontaneously responded with AP or BA behaviors toward conflicting emotional stimuli, and expressed yellow fluorescent protein (YFP) in pyramidal neurons of mPFC. Patch-clamp electrophysiological recordings showed that mPFC pyramidal neurons of AP mice had a significantly higher frequency. of spontaneous excitatory post-synaptic currents when compared with BA mice. YFP-expressing pyramidal neurons from mPFC of AP and BA mice have been sorted to purify cell-specific RNA for a transcriptome-wide analyses. The omic results showed differential gene expression between AP and BA mice in the pathways associated to the regulation of immune system. Namely, AP mice were characterized by a gene overexpression for immune system response pathways and a significant change in cell number and activation of specific peripheral and central immune cells such as CD3+ T lymphocytes and microglia. Overall, our findings suggest that in the mPFC both the increased excitatory neurotransmission and the altered immune response are crucial underpinnings of AP tendency