The GABAB1b isoform mediates long-lasting inhibition of dendritic Ca2+ spikes in layer 5 somatosensory pyramidal neurons

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 GABA(B) receptors was responsible for a gradual and long-lasting inhibitory effect, whereas GABA(A) receptors mediated a short-lasting (similar to 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 GABA(B1) isoforms, GABA(B1a). and GABA(B1b), we showed that postsynaptic inhibition of Ca2+ spikes is mediated by GABA(B1b), whereas presynaptic inhibition of GABA release is mediated by GABA(B1a). We conclude that the molecular subtypes of GABA(B) receptors play strategically different physiological roles in neocortical neurons.