Lamina-specific differences in GABA_B autoreceptor-mediated regulation of spontaneous GABA release in rat entorhinal cortex

Spontaneous synaptic inhibition plays an important role in regulating the excitability of cortical networks. Here we have investigated the role of GABA_B autoreceptors in regulating spontaneous GABA release in the entorhinal cortex (EC), a region associated with temporal lobe epilepsies. We have previously shown that the level of spontaneous inhibition in superficial layers of the EC is much greater than that seen in deeper layers. In the present study, using intracellular and whole cell patch clamp recordings in rat EC slices, we have demonstrated that evoked GABA responses are controlled by feedback inhibition via GABA_B autoreceptors. Furthermore, recordings of spontaneous, activity-independent inhibitory postsynaptic currents in layer II and layer V neurones showed that the GABA_B receptor agonist, baclofen, reduced the frequency of GABA-mediated currents indicating the presence of presynaptic GABA_B receptors in both layers. Application of the antagonist, CGP55845, blocked the effects of baclofen and also increased the frequency of GABA-mediated events above baseline, but the latter effect was restricted to layer V. This demonstrates that GABA_B autoreceptors are tonically activated by synaptically released GABA in layer V, and this may partly explain the lower level of spontaneous GABA release in the deep layer.