SYNAPTIC PLASTICITY NMDA Mediates Both LTD and LTP in the Retinotectal System

Lien et al. found that in the developing retinotectal system (visual system), both long-term depression (LTD) of inhibitory GABAergic inputs to the developing tectum and long-term potentiation (LTP) of the retinotectal synapse required activation of N-methyl-D-aspartate (NMDA)-type glutamate receptors. Light-induced excitatory and inhibitory compound synaptic currents (eCSCs and iCSCs), which were mediated by -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (AMPA/kainate)-type glutamate receptors and -aminobutyric acid type A (GABA_A) receptors, respectively. Conditioning (high frequency) light stimuli produced a long-term enhancement to the eCSCs, which was blocked in the presence of an NMDA receptor antagonist. Conditioning light stimuli also reduced the iCSCs, and this was also blocked in the presence of an NMDA receptor antagonist. To further define the mechanism of LTP and LTD in this system, monosynaptic currents were monitored using electrical stimuli, instead of light, with GABA mediating an inhibitory response and AMPA/kainate receptors mediating the excitatory response. Theta-burst stimulation (TBS) produced LTP and LTD in the synapses, and NDMA receptors were required for both. Although induction of LTP required activity of the postsynaptic neuron, induction of LTD of the GABAergic synapse did not require activity of the postsynaptic tectal neuron or postsynaptic NMDA receptor activation, which were blocked by application of an intracellular blocker administered to the postsynaptic cell with the recording pipette. Bath application of NMDA to the tectum increased the frequency of miniature inhibitory postsynaptic currents (mIPSCs) but decreased the amplitude of the current. The authors suggest that high-frequency stimulation of the retinotectal system activates the presynaptic glutamatergic neurons such that NMDA receptors on the postsynaptic neuron are stimulated and NMDA receptors on the adjacent GABAergic synapses are also stimulated by glutamate "spillover." This results in LTD of the inhibitory GABAergic input and LTP in the postsynaptic tectal neuron.

C.-C. Lien, Y. Mu, M. Vargas-Caballero, M.-m. Poo, Visual stimuli-induced LTD of GABAergic synapses mediated by presynaptic NMDA receptors. Nat. Neurosci. 9, 372-380 (2006). [PubMed]