Can heterosynaptic depression be mimicked pharmacologically?
Given the role of NMDA receptors in tetanus-induced heterosynaptic depression and Ca2+ activation of glial cells, we examined the effects of NMDA on fEPSPs and glial cell Ca2+ levels. Bath application of NMDA (25 µM) depressed fEPSPs to 4.2 ± 5.1% of baseline with a maximal reduction occurring at 16.8 ± 1.4 min after the onset of drug application (Fig. 2A). NMDA-induced depression was prevented by the NMDA receptor antagonist D-AP5 (50 µM; Student’s paired t test; p < 0.001) (Fig. 2A). Interestingly, the same NMDA application also caused a transient elevation of Ca2+ in glial cells (Fig. 2B). The relative increase of Ca2+ in glial cells reached a peak of 64.4 ± 4.3% ΔF/F, with a latency of 11.5 ± 0.5 min after the onset of NMDA application, and recovered to half-maximal effect at 14.4 ± 0.8 min after the onset of drug application. The slow kinetics of the Ca2+ responses may be the result of the bath application of the agonist (see also Porter and McCarthy, 1995; Kang et al., 1998). The
