Dissertation > Medicine, health > Neurology and psychiatry > Psychiatry > Neurosis

Roles of BKCa Channels in the Synaptic Plasticity in Amygdala

Author GuoYanYan
Tutor ZhaoMingGao
School Fourth Military Medical University
Course Pharmacology
Keywords BKCa long-term plasticity NMDA receptor amygdala
CLC R749.7
Type Master's thesis
Year 2010
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Anxiety is one of the most common mental disorders. Recent studies are focused on its pathogenesis and therapeutics. Large-conductance Ca2+ - activated K+ (BKCa) channels are highly expressed in the lateral amygdala (LA) and play key roles in regulation of neuronal excitability.The activation of channel can produce after-hyperpolarization potential (AHP) and decrease membrane excitability, thereby reducing the electrical activity of neurons on neurotransmitter release and neural network function. It plays an important role in regulating neuronal excitability. However, it is not known if membrane hyperpolarization induced by activation of BKCa channels has potential inhibitory effects on the local amygdala networks and the incidence of anxiety disorders.In present study, we investigated roles of BKCa channels in the neuronal excitability and synaptic transmission in the amygdala by using the electrophysiological, biological, and behavioral methods. It suggested that dysfunction of BKCa channels might be involved in the pathogenesis of anxiety disorders. AIMS(1) To clarify the role of BKCa channels in neuronal excitability and synaptic plasticity in the lateral amygdala.(2) To explore potential treatment targeted on BKCa channels.METHODS1) Whole-cell patch clamp technique was used to study the effects of BKCa channels on the excitability of pyramidal neurons, after hyperpolarization (AHP) and synaptic plasticity in hypothalamic pathway.2) Immunohistochemistry was applied to detect the expression of BKCa channels in the interneuron and pyramidal neuron in the lateral amygdala.3) Elevated plus-maze and open field tests were performed to exam the effects of BKCa channels on the formation of anxiety. Local micro-injection of specific BKCa channel agonist or blocker was used in the behavioral experiments.RESULTSOur results showed that BKCa channels and NMDARs were colocalized in interneurons and pyramidal neurons in the LA. Activation of BKCa channels induced after hyperpolarization (AHP) and regulated neuronal excitation. Intracellular application of BAPTA, a potent calcium chelator,could abolish the effects of BKCa channels on the neuronal excitability. Blockage of the BKCa channel with iberiotoxin significantly enhanced the evoked NMDA receptor-mediated EPSCs and LTP in the thalamic pathway; however, it did not alter the probability of presynaptic transmitter release. CONCLUSIONThese results show that BKCa channel and NMDARs are colocalized in interneurons and pyramidal neurons in the LA. Calcium influx from the NMDARs activates BKCa channels and regulates neuronal excitation. The results indicate that BKCa channels play a key role in synaptic plasticity in the amygdala.

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