Gabriel M, Taylor C
Department of Psychology, Beckman Institute for Advanced Science and Technology, Urbana, Illinois 61801, USA.
Ann N Y Acad Sci. 1998 Jun 21;846:194-212.
Cingulate cortex and related areas of the thalamus are critically involved in the mediation of discriminative avoidance learning, wherein rabbits step in response to an acoustic conditional stimulus (CS+) to avoid foot shock and they learn to ignore a different acoustic stimulus (CS-) not followed by shock. Studies of multi-unit neuronal activity recorded simultaneously in many cingulothalamic areas have documented massive learning-related neuronal firing changes during the course of behavioral acquisition. Stimulated by findings (this volume) of neurobiological changes in anterior cingulate cortex in rabbits exposed in utero to cocaine, we investigated behavioral learning and correlated neuronal activity in several cingulothalamic areas in cocaine-exposed rabbits. In an initial study, training-induced enhancement of cingulate cortical neuronal firing in response to the CS+ and CS- was abolished in rabbits exposed to cocaine in utero. Yet discriminative neuronal activity (greater firing in response to the CS+ than to the CS-) did develop during training, and behavioral learning was normal in the cocaine-exposed rabbits. In a second study, we reduced the salience of the CS+ and CS- by employing 200 msec CSs rather than standard 500 msec CSs. Early training-stage development of anterior cingulate cortical discriminative neuronal activity was abolished, the elicited neuronal discharge profiles were altered, and behavioral learning was impaired in rabbits exposed to cocaine, relative to saline-exposed controls. The specificity of these changes to low-salience CSs suggested that prenatal cocaine results in disturbed associative attentional processes of anterior cingulate cortex in adult rabbits. Consideration of the neuronal response profile alterations together with other reported neurobiological changes suggested that the cocaine-related attentional deficit is due to impaired dopaminergic afferent activation of GABA neurons in anterior cingulate cortex.
扣带回皮质和丘脑的相关区域在辨别性回避学习的调节中起着关键作用。在这种学习过程中，兔子会对听觉条件刺激（CS+）做出反应以避免足部电击，并学会忽略另一种不伴随电击的不同听觉刺激（CS-）。对多个扣带丘脑区域同时记录的多单位神经元活动的研究表明，在行为习得过程中，大量与学习相关的神经元放电发生了变化。受子宫内暴露于可卡因的兔子前扣带回皮质神经生物学变化研究结果（本卷）的启发，我们研究了可卡因暴露兔子几个扣带丘脑区域的行为学习和相关神经元活动。在最初的一项研究中，子宫内暴露于可卡因的兔子在训练诱导下，扣带回皮质神经元对CS+和CS-的放电增强被消除。然而，在训练过程中确实出现了辨别性神经元活动（对CS+的放电比对CS-的放电更强），并且可卡因暴露兔子的行为学习是正常的。在第二项研究中，我们通过使用200毫秒的CS而不是标准的500毫秒的CS来降低CS+和CS-的显著性。相对于生理盐水暴露的对照组，子宫内暴露于可卡因的兔子在前扣带回皮质辨别性神经元活动的早期训练阶段发育被消除，诱发的神经元放电模式发生改变，行为学习受损。这些变化对低显著性CS的特异性表明，产前可卡因会导致成年兔子前扣带回皮质的联想性注意力过程受到干扰。结合其他报道的神经生物学变化来考虑神经元反应模式的改变，表明与可卡因相关的注意力缺陷是由于前扣带回皮质中GABA神经元的多巴胺能传入激活受损所致。
