Modulation of NMDA receptors by ACh in the central nervous system

The effect of acetylcholine (ACh) on N-methyl-D-aspartate (NMDA)-induced responses in neurons acutely dissociated from the rat nucleus basalis of Meynert (nBM) was investigated with a conventional patch-clamp technique. The whole-cell recording revealed that NMDA-induced inward current (INMDA) consisted of transient peak and successive steady-state components. With outside-out recording, these components were shown to have the identical single channel conductance. Pretreating the nBM neurons with the low concentration of ACh suppressed the peak component of INMDA, whereas the high concentration potentiated it. The modulatory action of ACh was observed in nBM neurons dissociated from mature rats. The action was deficient, however, in those from immature animals. These results suggest that ACh is either an inhibitory or an excitatory modulator of glutamatergic transmission in the central nervous system.