Triggering of Arachidonic Acid Release from Mature Striatal Neurons by Associative Stimulation of Ionotropic (AMPA) and Quisqualate Receptors Coupled to Phospholipase C (Q_p)

Abstract

It has been proposed that memory is encoded in the brain through a permanent increase in strength of synapses due to an associative stimulation of pre- and post-synaptic activity (Eccles 1953; Hebb 1949). This is why the discovery of associative long-term potentiation (LTP) has been so attractive (for reviews, see Kennedy 1989; Nicoll et al. 1988). In some glutamatergic synapses, high frequency presynaptic stimulation — but also weak stimulation associated with depolarization of the post-synaptic membrane — produces LTP, i.e., an enhancement of the transmission efficacy that could last hours to weeks. The main events required for LTP induction are a presynaptic stimulation, which is needed for glutamate (Glu) release, associated with a postsynaptic depolarization produced either by a sustained high level of transmitter release or by stimulation of nearby excitatory synapses (Kennedy 1989). The discovery that the full activation of N-methyl-D-aspartate (NMDA) glutamatergic receptors is by itself an associative process requiring presynaptic stimulation to release the agonist glutamate and postsynaptic depolarisation to suppress the Mg⁺⁺ blockade of its channel (Nowak et al. 1984) indicates a primordial role for NMDA receptors in synaptic plasticity. Such a role is clearly demonstrated by the blockade of LTP by NMDA receptor antagonists.