Eccles Institute of Neuroscience Seminar Series: How GABAB receptor regulates neuronal excitability in the cerebral cortex?

Dr Jean-Didier Breton, Neuronal Integration Group, Eccles Institute of Neuroscience, JCSMR, ANU.

Inhibition in the central nervous system is primarily mediated by the release of the neurotransmitter GABA. GABA is responsible for slow inhibitory via the activation of the metabotropic GABAB receptor (G-protein Gi/o coupled receptor). This receptor is widely distributed throughout the brain, and plays an important role in physiology and disease. Classically, GABAB receptor-mediated inhibition activates G-protein coupled inwardly rectifying potassium channels: GIRK channels. By increasing membrane permeability to potassium, GABAB receptors play a crucial role in decreasing neuronal excitability (reduction of neuronal firing) via hyperpolarizing the resting membrane potential and reducing neuron input resistance. In addition, GABAB receptors can act presynaptically to inhibit voltage-dependent calcium channels and thereby modulate transmitters release. While this action of GABAB receptors was initially thought to only be important in presynaptic terminals, there is increasing evidence that GABAB receptors can also act to modulate voltage-dependent calcium channels in dendrites and spines. In the cerebral cortex, pyramidal neurones receive inhibitory inputs from several classes of inhibitory neurones targeting somatic, dendritic and axonal compartments. Because of its metabotropic nature and also because the GABAB receptor is widely expressed on pyramidal neurones, GABAB receptors can have diverse effects on neuronal excitability. In my talk I will discuss the importance of the postsynaptic localisation of GABAB receptors in regulating neuronal output. Indeed, different cellular mechanisms are recruited by GABAB receptors to induce inhibition at the somatic and dendritic compartment of pyramidal neurones. Furthermore, some of these mechanisms are also dependent on the external pH, leading to a potential role of the GABAB receptors in hypoxia.

Date & time

4–5pm 8 March 2013

Location

The Finkel Lecture Theatre The John Curtin School of Medical Research, Building 131, Garran Road, ANU

Contacts

 Danielle Khalidi
 +61 2 612 53926

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