Postsynaptic induction and presynaptic expression of long-term potentiation at excitatory synapses on layer 2/3 VIP interneurons in the somatosensory cortex

Aims

The complex function of the neocortex depends on neuronal circuits composed of highly interconnected excitatory (glutamatergic) neurons and diverse types of inhibitory (GABAergic) interneurons. Synaptic transmission between specific connection motifs undergoes plastic changes during learning process, however, 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 intestine polypeptide-expressing interneurons (VIP-INs) in the mouse somatosensory (barrel) cortex.

Methods

Acute brain slices were prepared from transgenic mice with fluorescently labeled VIP-INs. LTP was induced by a pairing protocol of postsynaptic depolarization with extracellular stimulation.

Results

The pairing protocol evoked LTP in L2/3 VIP-INs in control condition, however, pharmacological blocking GABAaR inhibition enhanced LTP. Looking for mechanisms of LTP induction, we found that LTP at excitatory connections to VIP-INs is dependent on metabotropic glutamate receptor type 1 (mGluR-1) and L-type voltage-gated calcium channels (L-type VGCC) but not on NMDARs nor mGluR-5. Next, we showed that mGluR-1 acts through G-coupled signaling, Src-family pathway, independently of transient receptor potential channels (TRPC). Analyses of paired-pulse ratio (PPR) and coefficient of variation (CV) indicated 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).

Conclusions

We dissected 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 learning process.

Highlights

• GABAaR blockage enhances LTP at excitatory inputs to VIP-INs

• LTP in VIP-INs is NMDAR-independent

• Induction of LTP in VIP-INs is mediated by mGluR-1 but not mGluR-5

• mGluR-1 acts through Src-family signaling pathway, independently of TRPC

• L-type VGCC provide calcium influx necessary for LTP induction

• eCBs but not BDNF act as retrograde signaling in LTP in VIP-INs