Excitatory synaptic transmission in hippocampal area CA1 is enhanced then reduced as chronic epilepsy progresses

Neurobiol Dis. 2021 Jul:154:105343. doi: 10.1016/j.nbd.2021.105343. Epub 2021 Mar 20.

Abstract

This study examines changes in synaptic transmission with progression of the chronic epileptic state. Male Sprague-Dawley rats (P40-45) were injected with either saline or pilocarpine. In rats injected with pilocarpine, status epilepticus ensued. Hippocampal slices were cut 20-60 days or 80-110 days post-treatment. Evoked and miniature EPSCs (mEPSCs) were recorded from CA1 pyramidal neurons using whole-cell voltage-clamp. Fiber volleys were also recorded from stratum radiatum. Evoked EPSCs from the pilocarpine-treated cohort showed enhanced amplitudes 20-60 days post-treatment compared to the saline-treated cohort, whereas mEPSCs recorded from the same age group showed no change in event frequency and a slight but significant decrease in mEPSC amplitude distribution. In contrast, comparing evoked EPSCs and mEPSCs recorded 80-110 days after treatment indicated reduced amplitudes from pilocarpine-treated animals compared to controls. mEPSC inter-event interval decreased. This could be explained by a partial depletion of the ready releasable pool of neurotransmitter vesicles in Schaffer collateral presynaptic terminals of the pilocarpine-treated rats. In both saline- and pilocarpine-treated cohorts, concomitant decreases in mEPSC amplitudes as time after treatment progressed suggest that age-related changes in CA1 circuitry may be partially responsible for changes in synaptic transmission that may influence the chronic epileptic state.

Keywords: Aging; EPSCs; Epilepsy; Fiber volleys; Hippocampus; Pilocarpine; Status epilepticus; Synaptic transmission; mEPSCs.

Publication types

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

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / physiopathology*
  • Chronic Disease
  • Disease Progression*
  • Epilepsy / chemically induced
  • Epilepsy / physiopathology*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Male
  • Muscarinic Agonists / toxicity
  • Pilocarpine / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Status Epilepticus / chemically induced
  • Status Epilepticus / physiopathology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*

Substances

  • Muscarinic Agonists
  • Pilocarpine