Fig. 2. Synaptic efficacy in the mPFC bidirectionally regulates social hierarchy.

Excitatory synaptic transmission in the mPFC is greater in social dominants than in subordinates. Synaptic potentiation induced by the expression of Ras or GluA4 in the mPFC increases social hierarchy, whereas social rank is decreased by the expression of Rap or R4Ct in the mPFC³¹. Glutamate and ATP released from astrocytes in the mPFC regulate synaptic efficacy, resulting in changes in social hierarchy⁵⁵. Antisense long noncoding RNA of synapsin II (AtLAS) regulates the expression of synapsin 2b (Syn2b), which binds to AMPA receptors (AMPARs) to inhibit the delivery of AMPARs to synapses, resulting in a reduction in social rank. However, the delivery of AMPARs to synapses by the expression of a membrane-permeable peptide (P-2B) via the fusion of the TAT sequence to the C-terminus of Syn2b disrupts the binding of Syn2b to AMPARs, resulting in an increase in social status⁶⁷. AMPAR trafficking to the synapse by the phosphorylation of Ser818 and Ser831 of the GluA1 subunit is highly correlated with social winning in the tube test⁶⁹.