Posluszny Anna, Liguz-Lecznar Monika, Turzynska Danuta, Zakrzewska Renata, Bielecki Maksymilian, Kossut Malgorzata
Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Warsaw, Poland.
Department of Neurochemistry, Institute of Psychiatry and Neurology, Warsaw, Poland.
PLoS One. 2015 Dec 7;10(12):e0144415. doi: 10.1371/journal.pone.0144415. eCollection 2015.
Experience-induced plastic changes in the cerebral cortex are accompanied by alterations in excitatory and inhibitory transmission. Increased excitatory drive, necessary for plasticity, precedes the occurrence of plastic change, while decreased inhibitory signaling often facilitates plasticity. However, an increase of inhibitory interactions was noted in some instances of experience-dependent changes. We previously reported an increase in the number of inhibitory markers in the barrel cortex of mice after fear conditioning engaging vibrissae, observed concurrently with enlargement of the cortical representational area of the row of vibrissae receiving conditioned stimulus (CS). We also observed that an increase of GABA level accompanied the conditioning. Here, to find whether unaltered GABAergic signaling is necessary for learning-dependent rewiring in the murine barrel cortex, we locally decreased GABA production in the barrel cortex or reduced transmission through GABAA receptors (GABAARs) at the time of the conditioning. Injections of 3-mercaptopropionic acid (3-MPA), an inhibitor of glutamic acid decarboxylase (GAD), into the barrel cortex prevented learning-induced enlargement of the conditioned vibrissae representation. A similar effect was observed after injection of gabazine, an antagonist of GABAARs. At the behavioral level, consistent conditioned response (cessation of head movements in response to CS) was impaired. These results show that appropriate functioning of the GABAergic system is required for both manifestation of functional cortical representation plasticity and for the development of a conditioned response.
大脑皮层中由经验引起的可塑性变化伴随着兴奋性和抑制性传递的改变。可塑性所必需的兴奋性驱动增加先于可塑性变化的发生,而抑制性信号的减少通常会促进可塑性。然而,在某些依赖经验的变化中也观察到抑制性相互作用的增加。我们之前报道,在涉及触须的恐惧条件反射后,小鼠桶状皮层中抑制性标记物的数量增加,同时接受条件刺激(CS)的触须排的皮层代表区扩大。我们还观察到条件反射伴随着GABA水平的升高。在此,为了探究未改变的GABA能信号对于小鼠桶状皮层中依赖学习的神经回路重连是否必要,我们在条件反射时局部降低桶状皮层中的GABA产生或减少通过GABAA受体(GABAARs)的传递。向桶状皮层注射谷氨酸脱羧酶(GAD)抑制剂3-巯基丙酸(3-MPA)可防止学习诱导的条件触须表征扩大。注射GABAARs拮抗剂gabazine后也观察到类似效果。在行为水平上,一致的条件反应(对CS做出的头部运动停止)受损。这些结果表明,GABA能系统的正常功能对于功能性皮层表征可塑性的表现以及条件反应的发展都是必需的。