title: Somatic and dendritic GABA(B) receptors regulate neuronal excitability via different mechanisms.
abstract: GABA(B) receptors play a key role in regulating neuronal excitability in the brain. Whereas the impact of somatic GABA(B) receptors on neuronal excitability has been studied in some detail, much less is known about the role of dendritic GABA(B) receptors. Here, we investigate the impact of GABA(B) receptor activation on the somato-dendritic excitability of layer 5 pyramidal neurons in the rat barrel cortex. Activation of GABA(B) receptors led to hyperpolarization and a decrease in membrane resistance that was greatest at somatic and proximal dendritic locations. These effects were occluded by low concentrations of barium (100 μM), suggesting that they are mediated by potassium channels. In contrast, activation of dendritic GABA(B) receptors decreased the width of backpropagating action potential (APs) and abolished dendritic calcium electrogenesis, indicating that dendritic GABA(B) receptors regulate excitability, primarily via inhibition of voltage-dependent calcium channels. These distinct actions of somatic and dendritic GABA(B) receptors regulated neuronal output in different ways. Activation of somatic GABA(B) receptors led to a reduction in neuronal output, primarily by increasing the AP rheobase, whereas activation of dendritic GABA(B) receptors blocked burst firing, decreasing AP output in the absence of a significant change in somatic membrane properties. Taken together, our results show that GABA(B) receptors regulate somatic and dendritic excitability of cortical pyramidal neurons via different cellular mechanisms. Somatic GABA(B) receptors activate potassium channels, leading primarily to a subtractive or shunting form of inhibition, whereas dendritic GABA(B) receptors inhibit dendritic calcium electrogenesis, leading to a reduction in bursting firing.
authors.affiliation: Eccles Institute of Neuroscience, The John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: Jean-Didier
authors.initials: JD
authors.lastname: Breton
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Stuart
mesh_terms: D000200:Action Potentials; D000818:Animals; D001464:Barium / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D003712:Dendrites / Q000378:metabolism / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism*; D013003:Somatosensory Cortex / Q000166:cytology / Q000502:physiology
chemical_list: D015220:Calcium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018080:Receptors, GABA-B; D001464:Barium