NMDA Receptor Alterations After Mild Traumatic Brain Injury Induce Deficits in Memory Acquisition and Recall

Neural Comput. 2021 Jan;33(1):67-95. doi: 10.1162/neco_a_01343. Epub 2020 Nov 30.

Abstract

Mild traumatic brain injury (mTBI) presents a significant health concern with potential persisting deficits that can last decades. Although a growing body of literature improves our understanding of the brain network response and corresponding underlying cellular alterations after injury, the effects of cellular disruptions on local circuitry after mTBI are poorly understood. Our group recently reported how mTBI in neuronal networks affects the functional wiring of neural circuits and how neuronal inactivation influences the synchrony of coupled microcircuits. Here, we utilized a computational neural network model to investigate the circuit-level effects of N-methyl D-aspartate receptor dysfunction. The initial increase in activity in injured neurons spreads to downstream neurons, but this increase was partially reduced by restructuring the network with spike-timing-dependent plasticity. As a model of network-based learning, we also investigated how injury alters pattern acquisition, recall, and maintenance of a conditioned response to stimulus. Although pattern acquisition and maintenance were impaired in injured networks, the greatest deficits arose in recall of previously trained patterns. These results demonstrate how one specific mechanism of cellular-level damage in mTBI affects the overall function of a neural network and point to the importance of reversing cellular-level changes to recover important properties of learning and memory in a microcircuit.

Publication types

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

MeSH terms

  • Brain / physiopathology
  • Brain Concussion / physiopathology*
  • Humans
  • Memory Disorders / physiopathology*
  • Mental Recall / physiology*
  • Nerve Net / physiopathology
  • Neural Networks, Computer*
  • Neuronal Plasticity / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Unsupervised Machine Learning

Substances

  • Receptors, N-Methyl-D-Aspartate