Somatic and dendritic GABAB receptors regulate neuronal excitability via different mechanisms
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Breton, Jean-Didier; Stuart, Greg
Description
GABAB receptors play a key role in regulating neuronal excitability in the brain. Whereas the impact of somatic GABAB receptors on neuronal excitability has been studied in some detail, much less is known about the role of dendritic GABAB receptors. Here, we investigate the impact of GABAB receptor activation on the somato-dendritic excitability of layer 5 pyramidal neurons in the rat barrel cortex. Activation of GABAB receptors led to hyperpolarization and a decrease in membrane resistance...[Show more]
dc.contributor.author | Breton, Jean-Didier | |
---|---|---|
dc.contributor.author | Stuart, Greg | |
dc.date.accessioned | 2014-01-10T02:06:02Z | |
dc.date.available | 2014-01-10T02:06:02Z | |
dc.identifier.issn | 0022-3077 | |
dc.identifier.issn | 1522-1598 | |
dc.identifier.uri | http://hdl.handle.net/1885/11164 | |
dc.description.abstract | GABAB receptors play a key role in regulating neuronal excitability in the brain. Whereas the impact of somatic GABAB receptors on neuronal excitability has been studied in some detail, much less is known about the role of dendritic GABAB receptors. Here, we investigate the impact of GABAB receptor activation on the somato-dendritic excitability of layer 5 pyramidal neurons in the rat barrel cortex. Activation of GABAB 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 GABAB receptors decreased the width of backpropagating action potential (APs) and abolished dendritic calcium electrogenesis, indicating that dendritic GABAB receptors regulate excitability, primarily via inhibition of voltage-dependent calcium channels. These distinct actions of somatic and dendritic GABAB receptors regulated neuronal output in different ways. Activation of somatic GABAB receptors led to a reduction in neuronal output, primarily by increasing the AP rheobase, whereas activation of dendritic GABAB receptors blocked burst firing, decreasing AP output in the absence of a significant change in somatic membrane properties. Taken together, our results show that GABAB receptors regulate somatic and dendritic excitability of cortical pyramidal neurons via different cellular mechanisms. Somatic GABAB receptors activate potassium channels, leading primarily to a subtractive or shunting form of inhibition, whereas dendritic GABAB receptors inhibit dendritic calcium electrogenesis, leading to a reduction in bursting firing. | |
dc.description.sponsorship | NHMRC | |
dc.format | 36 pages | |
dc.publisher | American Physiological Society | |
dc.rights | http://www.sherpa.ac.uk/romeo/issn/0022-3077/ From Sherpa/Romeo website as at 9/1/14: Author can archive pre-print (ie pre-refereeing) | |
dc.source | Journal of Neurophysiology 108.10 (2012):2810-2818 | |
dc.subject | GABA(B) receptor | |
dc.subject | excitability | |
dc.subject | GIRK channels | |
dc.subject | calcium channels | |
dc.subject | output gain | |
dc.title | Somatic and dendritic GABAB receptors regulate neuronal excitability via different mechanisms | |
dc.type | Journal article | |
local.identifier.citationvolume | 108 | |
dc.date.issued | 2012-09-05 | |
local.identifier.absfor | 110900 - NEUROSCIENCES | |
local.identifier.ariespublication | u4693331xPUB106 | |
local.publisher.url | http://www.the-aps.org/ | |
local.type.status | Submitted Version | |
local.contributor.affiliation | Stuart, Greg, ANU, Eccles Institute of Neuroscience, The John Curtin School of Medical Research | |
dc.relation | http://purl.org/au-research/grants/nhmrc/1009425 | |
local.bibliographicCitation.issue | 10 | |
local.bibliographicCitation.startpage | 2810 | |
local.bibliographicCitation.lastpage | 2880 | |
local.identifier.doi | 10.1152/jn.00524.2012 | |
dc.date.updated | 2015-12-08T09:15:33Z | |
local.identifier.scopusID | 2-s2.0-84869155440 | |
local.identifier.thomsonID | 000311226600014 | |
Collections | ANU Research Publications |
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