کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6019010 1186531 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Regular ArticleDual actions of brain-derived neurotrophic factor on GABAergic transmission in cerebellar Purkinje neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Regular ArticleDual actions of brain-derived neurotrophic factor on GABAergic transmission in cerebellar Purkinje neurons
چکیده انگلیسی

The ability to regulate inhibitory synapses is a critical feature of the nervous system and a growing body of evidence indicates that brain-derived neurotrophic factor (BDNF) acutely modulates the efficacy of GABA synaptic transmission. Although the neuronal potassium-chloride cotransporter 2 (KCC2) has been implied in this BDNF-induced ionic plasticity, the reports about actions of BDNF on GABA signaling remain conflicting. Here we show dual effects of BDNF on GABAergic synaptic transmission in Purkinje neurons in rat cerebellar slices. BDNF decreased the amplitude of evoked outward IPSCs postsynaptically. It induced a depolarizing shift in the reversal potential (EIPSC), which reduced the driving force for outward IPSCs. However, in the absence of KCC2 activity, BDNF directly potentiated rather than inhibited GABAA receptor, which was reflected by an increase in the amplitude of outward IPSCs. This action of BDNF coincided with its effect in increasing the amplitude of inward IPSCs. Furthermore, an interaction between GABAA receptor and KCC2 was revealed by co-immunoprecipitation. The effects of BDNF on both GABAA receptor and KCC2 were dependent on TrkB and also activation of cyclin-dependent kinase 5 (Cdk5). However, only the effect of BDNF on KCC2 activity was dependent on a rise of intracellular calcium. Taken together, these data highlight distinct actions of BDNF on KCC2 and GABAA receptor in the regulation of GABAergic synaptic transmission.

► BDNF exerts dual effects on GABAergic transmission postsynaptically. ► BDNF facilitates GABAA receptor and suppresses KCC2 activity. ► Both effects are TrkB and Cdk5 dependent. ► Only the effect on KCC2 activity is dependent on a rise of intracellular calcium. ► An interaction between GABAA receptor and KCC2 was found.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 233, Issue 2, February 2012, Pages 791-798
نویسندگان
, , , , , , , , , ,