Functional network changes in hippocampal CA1 after status epilepticus predict spatial memory deficits in rats

J Neurosci. 2012 Aug 15;32(33):11365-76. doi: 10.1523/JNEUROSCI.1516-12.2012.

Abstract

Status epilepticus (SE) is a common neurological emergency, which has been associated with subsequent cognitive impairments. Neuronal death in hippocampal CA1 is thought to be an important mechanism of these impairments. However, it is also possible that functional interactions between surviving neurons are important. In this study we recorded in vivo single-unit activity in the CA1 hippocampal region of rats while they performed a spatial memory task. From these data we constructed functional networks describing pyramidal cell interactions. To build the networks, we used maximum entropy algorithms previously applied only to in vitro data. We show that several months following SE pyramidal neurons display excessive neuronal synchrony and less neuronal reactivation during rest compared with those in healthy controls. Both effects predict rat performance in a spatial memory task. These results provide a physiological mechanism for SE-induced cognitive impairment and highlight the importance of the systems-level perspective in investigating spatial cognition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / pathology*
  • Disease Models, Animal
  • Electrodes, Implanted
  • Entropy
  • Image Processing, Computer-Assisted
  • Lithium / toxicity
  • Male
  • Maze Learning / physiology
  • Memory Disorders / diagnosis*
  • Memory Disorders / etiology*
  • Models, Neurological
  • Muscarinic Agonists / toxicity
  • Nerve Net / pathology
  • Neurons / physiology
  • Pilocarpine / toxicity
  • Predictive Value of Tests
  • Probability
  • Rats
  • Rats, Sprague-Dawley
  • Space Perception / physiology*
  • Statistics as Topic
  • Statistics, Nonparametric
  • Status Epilepticus / chemically induced
  • Status Epilepticus / complications*
  • Status Epilepticus / pathology*

Substances

  • Muscarinic Agonists
  • Pilocarpine
  • Lithium