title: Dual actions of brain-derived neurotrophic factor on GABAergic transmission in cerebellar Purkinje neurons.
abstract: 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 (E(IPSC)), which reduced the driving force for outward IPSCs. However, in the absence of KCC2 activity, BDNF directly potentiated rather than inhibited GABA(A) 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 GABA(A) receptor and KCC2 was revealed by co-immunoprecipitation. The effects of BDNF on both GABA(A) 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 GABA(A) receptor in the regulation of GABAergic synaptic transmission.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China. yinghuang@shmu.edu.cn
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Ho
authors.initials: H
authors.lastname: Ko
authors.forename: Zelda H
authors.initials: ZH
authors.lastname: Cheung
authors.forename: Ken K L
authors.initials: KK
authors.lastname: Yung
authors.forename: Tai
authors.initials: T
authors.lastname: Yao
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wang
authors.forename: Alexei
authors.initials: A
authors.lastname: Morozov
authors.forename: Ya
authors.initials: Y
authors.lastname: Ke
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Ip
authors.forename: Wing-Ho
authors.initials: WH
authors.lastname: Yung
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002531:Cerebellum / Q000378:metabolism / Q000502:physiology; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D009924:Organ Culture Techniques; D011689:Purkinje Cells / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D027981:Symporters / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*; D000096922:K Cl- Cotransporters
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011963:Receptors, GABA-A; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters