Circuit-selective properties of glutamatergic inputs to the rat prelimbic cortex and their alterations in neuropathic pain

Crystle J. Kelly, Marco Martina*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Functional deactivation of the prefrontal cortex (PFC) is a critical step in the neuropathic pain phenotype. We performed optogenetic circuit dissection to study the properties of ventral hippocampal (vHipp) and thalamic (MDTh) inputs to L5 pyramidal cells in acute mPFC slices and to test whether alterations in these inputs contribute to mPFC deactivation in neuropathic pain. We found that: (1) both the vHipp and MDTh inputs elicit monosynaptic excitatory and polysynaptic inhibitory currents. (2) The strength of the excitatory MDTh input is uniform, while the vHipp input becomes progressively stronger along the dorsal–ventral axis. (3) Synaptic current kinetics suggests that the MDTh inputs contact distal, while the vHipp inputs contact proximal dendritic sections. (4) The longer delay of inhibitory currents in response to vHipp compared to MDTh inputs suggests that they are activated by feedback and feed-forward circuitries, respectively. (5) One week after a peripheral neuropathic injury, both glutamatergic inputs are modified: MDTh responses are smaller, without evidence of presynaptic changes, while the probability of release at vHipp–mPFC synapses becomes lower, without significant change in current amplitude. Thus, dysregulation of both these inputs likely contributes to the mPFC deactivation in neuropathic pain and may impair PFC-dependent cognitive tasks.

Original languageEnglish (US)
Pages (from-to)2627-2639
Number of pages13
JournalBrain Structure and Function
Volume223
Issue number6
DOIs
StatePublished - Jul 1 2018

Funding

Funding This work was supported by Grants from the National Institutes of Health (Grant Number: NS064091).

Keywords

  • Channelrhodopsin
  • Connectivity
  • Hippocampus
  • Pyramidal cell
  • SNI
  • Thalamus

ASJC Scopus subject areas

  • Anatomy
  • General Neuroscience
  • Histology

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