Journal
JOURNAL OF NEUROSCIENCE
Volume 26, Issue 16, Pages 4236-4246Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4687-05.2006
Keywords
brain injury; executive function; dorsolateral prefrontal cortex; medial prefrontal cortex; delay cells; GABAergic inhibition; D-1 antagonist
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Funding
- NINDS NIH HHS [NS35457, NS049160] Funding Source: Medline
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Working memory (WM), the ability to transiently hold information in mind, is essential for high- level cognitive functions that are often impaired in brain- injured patients. The cellular and molecular mechanisms contributing to WM deficits, which can manifest in the absence of overt damage, in these patients are unknown. The function of the dorsolateral prefrontal cortex in humans and monkeys, and the medial prefrontal cortex (mPFC), in rodents is critical for WM. We demonstrate that controlled cortical impact injury of rats causes a long- lasting WM impairment that is associated with increased levels of the GABA- synthesizing enzyme glutamic acid decarboxylase 67 (GAD67) in the mPFC for up to 1 month after injury. A single administration of dopamine D-1 antagonists at 14 d after injury is sufficient to decrease GAD67 levels and restore WM for at least 1 week. These findings indicate that inhibition of prefrontal neuronal activity contributes to WM deficits and that strategies to reduce GAD67 expression can offer prolonged WM improvement in brain- injured patients.
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