• M M Hoskison, A N Moore, B Hu, S Orsi, N Kobori, and P K Dash.
• Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, The University of Texas Medical School, Houston, TX 77225, USA.
• Neuroscience. 2009 Mar 17;159(2):483-91.

AbstractThe prefrontal cortex is highly vulnerable to traumatic brain injury (TBI) resulting in the dysfunction of many high-level cognitive and executive functions such as planning, information processing speed, language, memory, attention, and perception. All of these processes require some degree of working memory. Interestingly, in many cases, post-injury working memory deficits can arise in the absence of overt damage to the prefrontal cortex. Recently, excess GABA-mediated inhibition of prefrontal neuronal activity has been identified as a contributor to working memory dysfunction within the first month following cortical impact injury of rats. However, it has not been examined if these working memory deficits persist, and if so, whether they remain amenable to treatment by GABA antagonism. Our findings show that working memory dysfunction, assessed using both the delay match-to-place and delayed alternation T-maze tasks, following lateral cortical impact injury persists for at least 16 weeks post-injury. These deficits were found to be no longer the direct result of excess GABA-mediated inhibition of medial prefrontal cortex neuronal activity. Golgi staining of prelimbic pyramidal neurons revealed that TBI causes a significant shortening of layers V/VI basal dendrite arbors by 4 months post-injury, as well as an increase in the density of both basal and apical spines in these neurons. These changes were not observed in animals 14 days post-injury, a time point at which administration of GABA receptor antagonists improves working memory function. Taken together, the present findings, along with previously published reports, suggest that temporal considerations must be taken into account when designing mechanism-based therapies to improve working memory function in TBI patients.

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