Neuroscience Letters, 80 (1987) 283 288 283 Elsevier Scientific Publishers Ireland Ltd. NSL 04827 Is activation of N-methyl-D-aspartate receptor gated channels sufficient to induce long term potentiation? R. Neuman, E. Cherubini and Y. Ben-Ari INSERM U29, H6pital de Port-Royal, Paris (France) (Received 22 January 1987; Revised version received and accepted 3 June 1987) Key words: Hippocampal slice; CA~; CA3; Magnesium; N-Methyl-D-aspartate receptor; Schaffer colla- teral Superfusion of hippocampal slices with Mg 2. free medium (2(~30 min) produced in CA~ interictal bursts and an enhancement of the Schaffer collateral synaptic response which persisted for over 2 h after return to control media. This long lasting effect, which was blocked by N-methyl-D-aspartate (NMDA) antagonists, was not associated with changes in postsynaptic cell excitability. A cut between CA3 and CA~, which blocked the bursts in CA~ (but not in CA3), also abolished the long lasting effects of Mg 2' free medium. It is concluded that the activation of NMDA receptors gated ionic channels is insufficient per se to induce a long term potentiation of synaptic transmission. Several lines of evidence suggest that N-methyl-D-aspartate (NMDA) receptors participate in the initiation of long-term potentiation (LTP) of the Schaffer collateral synaptic response. This region is rich in NMDA receptors [9, 11] and blockade of these receptors with D-2-amino-5-phosphonovalerate (APV) appears to antagonize the induction of LTP by tetanic stimulation without reducing the amplitude of con- trol EPSPs [3, 7, 15]. These and other observations have been offered as evidence that activation of NMDA receptor-gated ionic channels may be necessary for the induc- tion of LTP [4, 14]. These channels show a voltage-dependent blockade by Mg 2+ [I, 10]. It has been suggested that the intense synaptic activation, which occurs with teta- nic stimulation, may overcome the Mg 2+ blockade resulting in current flow through these channels; this in turn initiates LTP [4, 8, 14]. In the present study we have exam- ined whether removal of the Mg 2+ blockade, by superfusion with Mg 2 ~-free medium is sufficient to induce a long-term enhancement of synaptic transmission. Male Wistar rats (100-150 g) were used. Transverse 450/~m hippocampal slices were cut and transferred to a completely submerged chamber as described previously [6]. Briefly, slices were maintained at a temperature of 33 34°C and superfused (2 Corre.~ondence: Y. Ben-Aft, INSERM U29, H6pital de Port-Royal, 123 Boulevard de Port-Royal, 75014 Paris, France.