Fast-Spiking Interneurons Supply Feedforward Control of Bursting, Calcium, and Plasticity for Efficient Learning

Cell. 2018 Feb 8;172(4):683-695.e15. doi: 10.1016/j.cell.2018.01.005.

Abstract

Fast-spiking interneurons (FSIs) are a prominent class of forebrain GABAergic cells implicated in two seemingly independent network functions: gain control and network plasticity. Little is known, however, about how these roles interact. Here, we use a combination of cell-type-specific ablation, optogenetics, electrophysiology, imaging, and behavior to describe a unified mechanism by which striatal FSIs control burst firing, calcium influx, and synaptic plasticity in neighboring medium spiny projection neurons (MSNs). In vivo silencing of FSIs increased bursting, calcium transients, and AMPA/NMDA ratios in MSNs. In a motor sequence task, FSI silencing increased the frequency of calcium transients but reduced the specificity with which transients aligned to individual task events. Consistent with this, ablation of FSIs disrupted the acquisition of striatum-dependent egocentric learning strategies. Together, our data support a model in which feedforward inhibition from FSIs temporally restricts MSN bursting and calcium-dependent synaptic plasticity to facilitate striatum-dependent sequence learning.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcium Signaling / physiology*
  • Interneurons / cytology
  • Interneurons / metabolism*
  • Learning / physiology*
  • Mice
  • Mice, Transgenic
  • N-Methylaspartate / metabolism
  • Nerve Net / cytology
  • Nerve Net / metabolism*
  • Neuronal Plasticity / physiology*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism

Substances

  • N-Methylaspartate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid