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

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.

journal_name

Neural Comput

journal_title

Neural computation

authors

Gabrieli D,Schumm SN,Vigilante NF,Meaney DF

doi

10.1162/neco_a_01343

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

67-95

issue

1

eissn

0899-7667

issn

1530-888X

journal_volume

33

pub_type

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