The proposed project explores the hypothesis that ethanol impairs sustained visual attention by disrupting synaptic processing in the medial prefrontal cortex (mPFC). A series of experiments will systematically characterize the behavioral and neurophysiological components of the ethanol-induced attentional deficit, and then determine the extent to which the disruption of mPFC is due to an interaction of ethanol with cholinergic projections from the basal forebrain. The experiments will apply multiple single unit recording techniques to rats performing an operant procedure that closely models neuropsychological tests used in humans. The simultaneous assessment of mPFC neuronal activity and higher cognitive processes represents a new approach to understanding cognitive dysfunction associated with ethanol use. We have established that ethanol impairs sustained attention and that mPFC neural activity correlates with performance of a sustained attention task in rats. Preliminary data indicate that ethanol produces selective alterations in the neural correlates of performance in the sustained attention task. These studies will first establish the effects of low doses of ethanol on both attentional performance and single unit activity, then systematically investigate the role of basal forebrain cholinergic inputs to mPFC in these effects. With the advent of new neuroscientific techniques for monitoring brain activity, and more valid animal testing procedures, there are new opportunities for studying the brain mechanisms of ethanol intoxication. There is an urgent need for studies that relate the function of critical brain circuits to ongoing behavioral performance during the decline in cognition that follows acute exposure to ethanol. By revealing the precise neural mechanisms that underlie ethanol-induced attentional dysfunction, this research may ultimately provide clues that aid in the development of new strategies, treatments and interventions for alcohol abuse and alcoholism.
| Broussard, John I; Karelina, Kate; Sarter, Martin et al. (2009) Cholinergic optimization of cue-evoked parietal activity during challenged attentional performance. Eur J Neurosci 29:1711-22 |
