VIP-to-SST Cell Circuit Motif Shows Differential Short-Term Plasticity across Sensory Areas of Mouse Cortex

J Neurosci. 2025 Mar 26;45(13):e0949242025. doi: 10.1523/JNEUROSCI.0949-24.2025.

Abstract

Inhibition of GABAergic interneurons has been found to critically fine-tune the excitation-inhibition balance of the cortex. Inhibition is mediated by many connectivity motifs formed by GABAergic neurons. One such motif is the inhibition of somatostatin (SST)-expressing neurons by vasoactive intestinal polypeptide (VIP)-expressing neurons. We studied the synaptic properties of layer (L) 2/3 VIP cells onto L4 SST cells in somatosensory (S1) and visual (V1) cortices of mice of either sex using paired whole-cell patch-clamp recordings, followed by morphological reconstructions. We identified strong differences in the morphological features of L4 SST cells, wherein cells in S1 fell into the non-Martinotti cell (nMC) subclass, while in V1 presented with Martinotti cell (MC)-like features. Approximately 40-45% of tested SST cells were inhibited by VIP cells in both cortices. While unitary connectivity properties of the VIP-to-nMC and VIP-to-MC motifs were comparable, we observed stark differences in short-term plasticity. During high-frequency stimulation of both motifs, some connections showed short-term facilitation while others showed a stable response, with a fraction of VIP-to-nMC connections showing short-term depression. We thus provide evidence that VIP cells target morphological subclasses of SST cells differentially, forming cell-type-specific inhibitory motifs.

Keywords: Martinotti cell; non-Martinotti cell; plasticity; short-term depression; short-term facilitation; somatosensory cortex; somatostatin; vasoactive intestinal polypeptide; visual cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Interneurons / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Net* / physiology
  • Neural Inhibition / physiology
  • Neuronal Plasticity* / physiology
  • Patch-Clamp Techniques
  • Somatosensory Cortex* / cytology
  • Somatosensory Cortex* / physiology
  • Somatostatin* / metabolism
  • Somatostatin* / physiology
  • Vasoactive Intestinal Peptide* / metabolism
  • Vasoactive Intestinal Peptide* / physiology
  • Visual Cortex* / cytology
  • Visual Cortex* / physiology

Substances

  • Vasoactive Intestinal Peptide
  • Somatostatin