title: The GABAB1b isoform mediates long-lasting inhibition of dendritic Ca2+ spikes in layer 5 somatosensory pyramidal neurons.
abstract: The apical tuft of layer 5 pyramidal neurons is innervated by a large number of inhibitory inputs with unknown functions. Here, we studied the functional consequences and underlying molecular mechanisms of apical inhibition on dendritic spike activity. Extracellular stimulation of layer 1, during blockade of glutamatergic transmission, inhibited the dendritic Ca2+ spike for up to 400 ms. Activation of metabotropic GABAB receptors was responsible for a gradual and long-lasting inhibitory effect, whereas GABAA receptors mediated a short-lasting (approximately 150 ms) inhibition. Our results suggest that the mechanism underlying the GABAB inhibition of Ca2+ spikes involves direct blockade of dendritic Ca2+ channels. By using knockout mice for the two predominant GABAB1 isoforms, GABAB1a and GABAB1b, we showed that postsynaptic inhibition of Ca2+ spikes is mediated by GABAB1b, whereas presynaptic inhibition of GABA release is mediated by GABAB1a. We conclude that the molecular subtypes of GABAB receptors play strategically different physiological roles in neocortical neurons.
authors.affiliation: Institute of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland.
authors.forename: Enrique
authors.initials: E
authors.lastname: Pérez-Garci
authors.forename: Martin
authors.initials: M
authors.lastname: Gassmann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bettler
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Larkum
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009433:Neural Inhibition / Q000502:physiology*; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D018080:Receptors, GABA-B / Q000378:metabolism; D013003:Somatosensory Cortex / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D002118:Calcium