ASPARTATE AND GLUTAMATE MEDIATE EXCITATORY SYNAPTIC TRANSMISSION IN AREA CA1 OF THE HIPPOCAMPUS

We examined whether L-aspartate (ASP) and L-glutamate (GLU) both funct ion as endogenous neurotransmitters in area CA1 of the rat hippocampus . Radioligand displacement experiments using L-a-amino-3-hydroxy-5-met hylisoxa-zole-4-propionic acid (H-3-AMPA) to label AMPA/kainate recept ors and H-3-cis-4-phosphonomethyl-2-piperidine carboxylic acid (H-3-CG S-19755) to label NMDA receptors confirmed that GLU (K(i) approximatel y 500 nm) but not ASP (K(i) > 1 mm) has high affinity for AMPA/kainate receptors whereas GLU (K(i) approximately 250 nm) and ASP (K(i) appro ximately 1.3 mum) both have high affinity for NMDA receptors. Elevatin g extracellular potassium concentration (50 mm, 1 min) evoked the calc ium-dependent release of both ASP (approximately 50% increase) and GLU (approximately 200% increase) from hippocampal slices and from minisl ices of area CA1. Reducing extracellular glucose concentration (0.2 mm ) reduced GLU release, enhanced ASP release, and reduced AMPA/kainate receptor-mediated responses more than NMDA receptor-mediated responses (to 7% and 34% of control, respectively). Fiber volleys, antidromic p opulation spikes, membrane potential, input resistance, and ATP conten t all were not affected by glucose reduction. Unlike low glucose, the inhibitory neuromodulator adenosine (5 mum), which reduces ASP and GLU release to a similar extent, reduced AMPA/kainate and NMDA receptor-m ediated population EPSPs similarly (to 11% and 12% of control, respect ively). AMPA/kainate and NMDA receptor-mediated population EPSPs were also similarly reduced by 0.4 mum TTX (to 32% and 22% of control, resp ectively) and similarly enhanced by 10 mum 4-aminopyridine (to 206% an d 248% of control, respectively). Finally, NMDA receptor-mediated EPSC s measured by whole-cell recording decayed faster in low glucose (73 m sec vs 54 msec) but not in adenosine (73 msec vs 78 msec). Together, t hese results confirm that ASP and GLU are both involved in excitatory synaptic transmission at the Schaffer collateral-commissural terminals in area CA1 of the rat hippocampus.