Somatic and dendritic GABA_B receptors regulate neuronal excitability via different mechanisms

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.