|Budget Amount *help
¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1997 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1996 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Working memory is a brain system for the temporary storage and manipulation of information, and is critical for various cognitive operations, such as reasoning, planning and problem-solving. Whereas it is well known that dorsolateral regions of the prefrontal cortex (PFC) are involved in working memory, its neurochemical basis is poorly understood yet. Recently, noradrenaline and its alpha_2-adrenergic receptors in the dorsolateral PFC have been implicated in working memory, but direct or significant evidence on this hypothesis is lacking.
To address this problem, we have performed a series of study in monkeys ; 1) studies combining intracerebral microinjections of noradrenaline antagonists with an oculomotor delayd-response (ODR) task, and 2) studies combining iontophoretic analysis of noradrenaline with single-neuron recording during the ODR task. The ODR task is sensitive to working memory, and a subset of PFC neurons show directional delay-period activity which represents a "memory
filed" for visuospatial working memory processes.
In the present studies, we found that 1) local injections of yohimbine, an alpha_2-adrenergic receptor antagonist, into the dor S olateral PFC induced a specific deficit on ODR performance, whereas alpha_1-adrenergic receptor anatagonist prazosin or beta-adrenergic receptor anatagonist propranolol did not have any clear effect ; and 2) iontophoretic applications of yohimbine, but not prazosin or propranolol, attenuated significantly and preferentially directional delay-period activity in PFC neurons during ODR performance.
These findings are first to provide significant and direct evidence on the involvement of alpha_2-adrenergic receptors in working memory processes mediated by the dorsolateral PFC.Sufficient/adequate activation of alpha_2-adrenergic receptors in the dorsolateral PFC are suggested to be required for maintaining/facilitating neuronal activities for working memory processes ; without such an activation, working memory is attenuated or lost and behavioral tasks requiring this cognitive function are poorly performed. Since dysfunction of alpha_2-adrenergic receptors in the PFC is evident in working memory deficits which accompany some mental disorders, such as schizophrenia and Korsakoff's amnesia, as well as aging, the present data may be useful for understanding, at the cellular level, cognitive deficits/declines associated with such mental disorders and aging. Less