Presynapic N-methyl-D-aspartate (NMDA) receptors regulate neurotransmission at excitatory synapses in rat visual cortex

 

P. Taneja*, P.J. Sjöström, G.G. Turrigiano, and S.B. Nelson

Dept. of Biology, Brandeis University, Waltham, MA 02454.

 

In addition to contributing postsynaptic currents, NMDA receptors (NMDARs) can occur presynaptically. Here we investigate their function at excitatory synapses onto layer 5 (L5) and L2/3 pyramidal neurons of rat visual cortex.

In L5 thick tufted pyramidal cells, APV (200 ÁM) reversibly reduced the frequency (66▒5%, p<0.0001, n=12) but not the amplitude (p=0.85) of spontaneous AMPA mEPSCs, suggesting that NMDARs normally elevate mEPSC frequency, perhaps by contributing to the resting calcium levels in the presynaptic terminal. APV also reversibly reduced AMPA mEPSC frequency (69.9▒0.4%, p<10-6, n=6) in L2/3 pyramids, without affecting amplitude (p=0.97). Consistent with no activation of postsynaptic NMDARs (holding potential = -90mV, 1mM Mg2+), mEPSC decay time course was not altered (p=0.99).

To examine the functional role of presynaptic NMDARs, we studied the effects of NMDAR blockers (APV, MK801, or ifenprodil) on evoked neurotransmission in L5-to-L5 pairs. Wash-in of NMDAR blockers reduced AMPA receptor mediated responses evoked by 30 Hz (after/before=48▒5%, n=17), but not 0.1 Hz (105▒5%, n=15; p<10-8) spiking. Switching from 0.1 to 30 Hz firing for 15 min suppressed neurotransmission in the presence of MK801 (77.9▒2.8%, n=3), but not in control experiments (100▒6.3%, n=4; p<0.05), suggesting that the presynaptic NMDARs are necessary for maintenance of neurotransmission during high-frequency firing.

In L5 pairs, the NR2B-specific NMDAR blocker ifenprodil reduced neurotransmission evoked at 30 Hz (51▒10%, n=4), but not at 0.1 Hz (103▒6.6%, n=6; p<0.01) in P14-P16 rats. At this age, postsynaptic NMDARs are no longer ifenprodil sensitive. Ifenprodil wash-in did not affect the NMDA:AMPA ratio (103▒6%, p=0.62, n=4), although MK801/APV did (83▒6%, n=15; p<0.05). Hence if presynaptic NMDARs undergo a developmental subunit switch, it occurs at a later age compared to postsynaptic NMDARs.

(This research was funded by NIH)