ADULT THALAMOCORTICAL TRANSMISSION INVOLVES BOTH NMDA AND NON-NMDA RECEPTORS

1. The involvement of N-methyl-D-aspartate (NMDA) receptors in thalamo cortical transmission has been demonstrated in early postnatal develop ment, but could not be determined so far in adult animals. We used tha lamocortical slices from brains of mature mice to examine whether NMDA receptors exist in adult thalamocortical synapses, and what is their potential contribution to thalamocortical synaptic responses. 2. Thala mocortical fibers to the primary somatosensory area of the cortex were stimulated by an electrode placed in the ventrobasal (VB) nucleus of the thalamus. Horizontal intracortical axons within layer 5 were stimu lated for comparison: a cut was made in the slice between layers 4 and 5 lateral to the recording area, and a second stimulating electrode w as placed under the cut to activate these fibers. 3. Mg2+-free perfusi ng solution was used to enhance NMDA-receptor-mediated excitatory post synaptic potentials (EPSPs). It led to synchronized population events that could be evoked by stimulating either in the thalamus or in layer 6. A short-latency, monosynaptic EPSP preceded the synchronous events in layer 5 cells. 4. Bath application of the non-NMDA antagonist 6-cy ano-7-nitroquinoxaline-2,3-dione (CNQX, 10 mu M) abolished only synchr onized events triggered from the thalamus, but not intracortically. CN QX reduced, but did not abolish, the monosynaptic thalamocortical EPSP , and had almost no effect on intracortically evoked EPSPs. Focal appl ication of the gamma-aminobutyric acid-A receptor antagonist bicuculli ne methiodide (10 mu M) to layer 4 reestablished the appearance of syn chronous events on thalamic stimulation. 5. Monosynaptic thalamocortic al and intracortical EPSPs on the same cells were studied in the prese nce of normal Mg2+ concentration to mimic better the physiological sta te. Spikes were abolished by intracellular injection of the quarternar y lidocaine derivative (QX-314) sodium channel blocker. EPSPs from bot h sources were reduced compared with control, but not blocked, after b ath application of CNQX (10 mu M). CNQX-resistant EPSPs of both synapt ic tracts were evident at membrane potentials close to rest, exhibited strong voltage dependency, and were blocked by the NMDA antagonist DL -2-amino-5-phosphonovaleric acid (APV), suggesting that they were NMDA receptor dependent. 6. To confirm that NMDA receptors were indeed act ivated at thalamocortical synapses and not by antidromic activation of intracortical pathways, we used pressure microapplications of glutama te (10 mM) to the VB nucleus of the thalamus. The perfusing solution c ontained CNQX (10 mu M) and cells were recorded with micropipettes con taining QX-314. All cells that showed a monosynaptic response to elect rical thalamic stimulation also exhibited a barrage of mixed synaptic responses to thalamic glutamate application. The amplitude of these sy naptic events was dependent strongly on the membrane voltage, and the application of APV to the cortex abolished the events completely. 7. O ur results demonstrate that, in adult animals, both thalamocortical an d intracortical synaptic pathways utilize NMDA as well as non-NMDA rec eptors.