The GABA B1b Isoform Mediates Long-Lasting Inhibition of Dendritic Ca 2+ 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 Ca 2+ 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 (∼150 ms) inhibition. Our results suggest that the mechanism underlying the GABA B inhibition of Ca 2+ spikes involves direct blockade of dendritic Ca 2+ channels. By using knockout mice for the two predominant GABA B1 isoforms, GABA B1a and GABA B1b, we showed that postsynaptic inhibition of Ca 2+ 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.