NE and ACh workshop 2004

ABSTRACTS

Venue
B10 Seminar Room, Alexandra House, 17 Queen Square
London, WC1N 3AR

There appears little doubt that both acetylcholine (ACh) and noradrenaline (NA) modulate cellular excitability and function in the mammalian cerebral cortex yet it remains poorly understood how these effects are mediated precisely and whether cortically-projecting ACh and NA neurons are engaged by distinct psychological processes. This presentation focuses on functional neurochemical studies in laboratory rats using in-vivo microdialysis, specifically within the context of visual attentional function as assessed by performance of subjects on a 5-choice serial reaction time task (5-CSRTT). The task requires subjects to distribute attentional resources across a spatial array to detect successfully the occurrence of brief visual stimuli over a large number of discrete trials. Evidence will be presented for functional dissocations in ACh and NA release in the prefrontal cortex under defined conditions, specifically during schedules where reinforcement for correct target detection is made either contingent or non-contingent on the subject’s behaviour. These effects are compared are contrasted with prefrontal DA and 5-HT release during performance on a variant of this task as well as performance on a task that places less explicit demands on attentional processing, namely a delay-of-reward test of choice impulsivity. The necessity of the prefrontal cholinergic system to attentional performance is also addressed by an examination of the effects of selective depletion of ACh from the prefrontal cortex using 192 IgG-saporin, the cholinergic immunotoxin. Finally, the possible relevance of these findings to the cognitive sequalae of intravenously self-administered amphetamine will be discussed.

Supported by the Wellcome Trust within the Cambridge MRC Center in Behavioural and Clinical Neuroscience.