Regulation of long-term potentiation by presynaptic glutamate receptors in inhibitory connections of visual cortex

Abstract

Analysis of miniature inhibitory postsynaptic currents (IPSCs) suggested the presence of non-NMDA and NMDA receptors at the presynaptic terminals of inhibitory connections in layer 2/3 pyramidal neurons of mouse visual cortex. We investigated the role of these presynaptic receptors in long-term potentiation (LTP) of IPSCs recorded from layer 2/3 pyramidal neurons. High-frequency-stimulation (HFS) of presynaptic fibers, which was applied while membrane potential was held at -70 mV to avoid Ca²⁺ entry into postsynaptic neurons, produced LTP of IPSCs recorded at the reversal potential of excitatory synaptic transmission (0 mV) in a normal solution. In the presence of the non-NMDA receptor antagonist NBQX, HFS produced LTP of IPSCs recorded at -70 mV, at which postsynaptic NMDA receptors are not activated, although the magnitude of LTP was smaller, compared with the control solution. In the presence of the NMDA receptor antagonist APV or the NR2B-selective NMDA receptor antagonist Ro 25-6981 together with NBQX, HFS failed to produce LTP. Even in the presence of NBQX and APV, HFS produced LTP in the solution containing a high concentration (4 mM) of Ca²⁺. Our previous study demonstrated the requirement of action potential-associated Ca²⁺ entry through voltage-gated Ca²⁺ channels into presynaptic terminals for the maintenance of LTP. Taken together, it is likely that presynaptic Ca²⁺ entry through NMDA receptors, in addition to the entry through voltage-gated Ca²⁺ channels, contributes to the maintenance of LTP. [J Physiol Sci. 2007;57 Suppl:S18]