Pre- and post-synaptic functions of kainate receptors at glutamate and GABA synapses in the rat entorhinal cortex

Oscillatory network activity in cortical areas is seen as vital to physiological processes of cognition, learning, and memory, and fundamental to disorders such as epilepsy. Increasing attention is being paid to the role of kainate receptors (KAr) in the generation of network oscillations and synchrony. The entorhinal cortex (EC) plays a key role in learning and memory, and is a major site of dysfunction in temporal lobe epilepsy. KAr have been implicated in oscillogenesis in the EC, but limited information is available concerning the physiological roles of KAr in synaptic transmission in this area. Here, we make a detailed analysis of KAr function in Layer III of the EC, a site known to be highly susceptible to oscillogenesis, using whole-cell patch clamp recording of evoked and spontaneous synaptic currents in rat brain slices. We demonstrate that KAr containing the GluK1-subunit act as facilitatory autoreceptors at glutamatergic synapses on pyramidal neurones in Layer III. In addition, GluK1-containing KAr mediate an excitatory drive at glutamatergic synapses on GABAergic interneurones. In contrast, a different KAr, which is likely to contain the GluK2-subunit mediates a slow postsynaptic excitation at glutamatergic synapses on principal neurones, and may also act as a heteroreceptor, facilitating GABA release at inhibitory terminals on principal neurones. Reducing [Mg(2+) ](o) , which we have previously shown can generate KAr-dependent slow network oscillations in Layer III, enhances both glutamate and GABA release. Both effects are partly sustained by increased activation of GluK1-containing KAr. Increased activation of the GluK1-containing autoreceptor also results in an enhancement of the postsynaptic response mediated by GluK2-containing receptors. Finally, spontaneous release of both transmitters shows a rhythmic periodicity in low-Mg, and, again, this is dependent on GluK1-containing KAr. The results show that KAr contribute a facilitatory function at multiple levels in the networks of the EC, and provide a basis for dissecting the role of these receptors in oscillogenesis in this area.