Postsynaptic Induction and Presynaptic Expression of Long‐Term Potentiation at Excitatory Synapses on Layer 2/3 VIP Interneurons in the Somatosensory Cortex

Synaptic transmission between specific connection motifs undergoes plastic changes during the learning process; however, the exact mechanisms underlying synaptic plasticity are still under intense investigation. Long-term potentiation (LTP) of synaptic transmission is a widely used cellular model of synaptic plasticity occurring during learning. Here, we focused on studying LTP at excitatory synapses on layer (L) 2/3 vasoactive intestinal polypeptide-expressing interneurons (VIP-INs) in the mouse somatosensory (barrel) cortex. LTP was induced by a pairing protocol of postsynaptic depolarization with extracellular stimulation in acute brain slices of young mice (P21-P28). The pairing protocol evoked LTP in L2/3 VIP-INs under control conditions; however, pharmacological blockade of GABAaR inhibition enhanced LTP. Next, we found that LTP in L2/3 VIP-INs is dependent on metabotropic glutamate receptor type 1 (mGluR-1) and L-type voltage-gated calcium channels (L-type VGCCs) but not on NMDARs or mGluR-5. Here, mGluR-1 acts through a G-protein-coupled signaling pathway and Src-family kinases, independently of transient receptor potential channels (TRPCs). Analyses of the paired-pulse ratio (PPR) and coefficient of variation (CV) indicate a presynaptic locus of LTP expression. Presynaptic expression of LTP in VIP-INs relies on retrograde signaling through endocannabinoids (eCBs) but not on brain-derived neurotrophic factor (BDNF). In conclusion, we dissected the mechanisms of LTP induction and expression at excitatory inputs to L2/3 VIP-INs in the mouse barrel cortex. LTP at excitatory synapses on VIP-INs might serve as a positive feedback for enhanced VIP-IN-mediated inhibition of SST-INs, leading to disinhibition of excitatory neurons from SST-IN inhibition during the learning process.