Anthony A. Grace 教授 講演会

日時：　 平成１８年８月２日（水曜日）
　　　　　　午後４時―午後５時半

場所：　 京都大学　総合人間学部棟　１階　１１０３講義室
　　　　　　　　　（京都大学吉田南キャンパス内、東一条通側入り口から入ってすぐの 左側の建物）

講演者：　 Anthony A. Grace 教授 　
　　　　　　Professor of Neuroscience, Psychiatry, and Psychology University of Pittsburgh, USA.

タイトル： Prefrontal cortical-limbic system interactions and the pathophysiology of psychiatric disorders

講演概要： The amygdala is a brain region involved in the expression of emotions as well as in learning of the association between stimuli and emotional responses. The amygdala is comprised of two segments: the basolateral amygdala (BLA) which has connections with areas involved in emotional and cognitive aspects of fear, and the central amygdala (CeA), which is more involved in autonomic responses. The prefrontal cortex (PFC) is known to play an important role in the modulation of responses within the amygdala, in that stimulation of the PFC will attenuate responses of BLA neurons to noxious stimuli. This is done by PFC activation of interneurons within the BLA, which in turn inhibit the output of this structure. With respect to behavior, the PFC is proposed to play a role in attenuating responses to benign stimuli or to prevent the system from responding inappropriately to nonthreatening situations. However, if the PFC is not functioning correctly, as is proposed to occur in schizophrenia or affective disorders, this suppression does not occur. Under this situation, the otherwise benign stimuli would take on threatening properties; such a condition may be analogous to paranoia.

     Another important function of the amygdala is to mediate responses to maintained stressors. We examined the effects of acute (footshock) and chronic (cold stress; 14 days at 5 degrees C) stress on the electrophysiological activity of neurons within the amygdala. Following chronic cold exposure, BLA neuronal firing rate is not significantly different from baseline; however, there is an increase in the number of spontaneously active neurons. Moreover, the activation produced by a mild footshock is markedly enhanced in these rats. Therefore, chronic stress makes the BLA more responsive to stimuli, with more active neurons capable of responding rapidly, and the amplitude of the response enhanced. In contrast, CeA neurons show a decrease in firing rate and activity levels; nonetheless, the CeA also exhibits a markedly enhanced response to acute footshock. The CeA response appears to be potently modulated by the PFC; lesions of prefrontal cortical afferents in control rats produces effects that are similar to that observed with chronic cold; there is an attenuation of baseline activity and a markedly greater response to footshock. Therefore, following chronic cold, the amygdala activity resembles that observed in rats with deficits in prefrontal cortical function. Although it is important for an organism to maintain heightened cognitive responses in stressful environments (via BLA), an overdrive of the autonomic system (via CeA) secondary to PFC dysfunction can have deleterious consequences. As a result, an underlying PFC deficit could lead to overdrive of the autonomic system and pathology within stress-sensitive structures within the brain.

     This could have important implications with respect to psychiatric disorders. A deficit in the ability of the PFC to attenuate responses within the amygdala would cause an individual to show abnormally heightened responses to stressors. A maintained over-stimulation of these stress-related systems could lead to pathology within sensitive brain regions, such as the hippocampus. Therefore, an underlying dysfunction in the PFC could lead to disruption within the hippocampus, and may be a precipitating factor in disorders such as schizophrenia.

問い合わせ先：　京都大学大学院人間・環境学研究科認知・行動科学講座
　　　　　　　　　　　船橋新太郎　e-mail: h50400@sakura.kudpc.kyoto-u.ac.jp

後援：　２１世紀ＣＯＥプログラム『心の働きの総合的研究教育拠点』