The role of ionotropic glutamate receptors in memory formation after a passive avoidance task in the domestic chick (Gallus domesticus).

Abstract

Memory formation depends on alterations in synaptic morphology, and specific L-glutamate receptor subtypes (NMDA and AMPA receptors) are known to play a key role insuch synaptic plasticity. Changes in binding of neurotransmitters to discrete populations of receptors, in specific brain regions, could directly subserve memory related increases in synaptic efficacy. The cellular correlates of memory formation have been extensively studied in the chick brain, using one trial passive avoidance training. Alterations in receptor binding can be studied using quantitative autoradiography in conjunction with this paradigm. Also, this paradigm can be used to study the behavioural responses of chicks to drugs which act at specific receptors. These techniques were used to investigate the effect of passive avoidance on the binding characteristics of ionotropic L-glutamate receptors at specific times post-training, and of drug injections on the avoidance response. Pre-training intracerebral injection of NMDA receptor antagonists (MK-801, 7-ClK) were found to block the early stages of memory formation, whereas AMPA receptor antagonists did not. Injection of an AMPA receptor antagonist (CNQX) 4.5 or 5.5 h after training, however, blocked memory retention at 6.5 h. Autoradiographic data indicated the presence of two NMDA receptor subtypes in the chick forebrain, NMDA and CPP preferring receptors. The binding properties of these were found to be altered 30 min and 3 h after passive avoidance training. 30 min post-training, increased binding to NMDA receptors was found in the left IMHV and left LPO. At 3 h post-training increased numbers of nNMDA receptors were detected in the hippocampus and left AIv, whilst the affinity of cNMDA receptors increased in the AIv. The only alterations in the binding properties of AMPA receptors were at 6.5 h post-training, when increases in their affinity were found bilaterally in the IMHV and in the left PA (see abbreviations).