Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε1 subunit

Abstract

The NMDA (N-methyl-D-aspartate) receptor channel is important for synaptic plasticity, which is thought to underlie learning, memory and development. The NMDA receptor channel is formed by at least two members of the glutamate receptor (GluR) channel subunit families, the GluR epsilon (NR2) and GluR zeta (NR1) subunit families. The four epsilon subunits are distinct in distribution, properties and regulation. On the basis of the Mg2+ sensitivity and expression patterns, we have proposed that the epsilon 1 (NR2A) and epsilon 2 (NR2B) subunits play a role in synaptic plasticity. Here we show that targeted disruption of the mouse epsilon 1 subunit gene resulted in significant reduction of the NMDA receptor channel current and long-term potentiation at the hippocampal CA1 synapses. The mutant mice also showed a moderate deficiency in spatial learning. These results support the notion that the NMDA receptor channel-dependent synaptic plasticity is the cellular basis of certain forms of learning.

Pb2+ reduces the current from NMDA receptors expressed in Xenopus oocytes

“…Mice lacking the el subunit have reduced hippocampal LTP and spatial learning [22], The E1/(I receptor is postnatally expressed and widely distributed in the brain and e4/(l receptors are present in the diencephalon and brainstem from the embryonic, through the neonatal stage [7]. Both the receptors were inhibited by Pb 2+ at the low concentration shown in the present experiment.…”

Acetyl l-carnitine protects motor neurons and Rohon-Beard sensory neurons against ketamine-induced neurotoxicity in zebrafish embryos

“…Activation of NMDARs is essential for long-term potentiation and spatial learning and memory (Malenka and Bear, 2004), and NMDAR blockade results in impaired synaptic plasticity manifested as adverse effects on learning and memory (Sakimura et al, 1995;Shimizu et al, 2000). It has been shown that higher doses of ketamine can induce neuroapoptosis in rodents (Maxwell et al, 2006;Olney et al, 2002a;Wang et al, 2005) and primates (Haberny et al, 2002;Slikker et al, 2007b;Wang et al, 2006) during early development.…”

The impact of blood pressure on hippocampal glutamate and mnestic function

“…For example, dysfunction or blockade of the NMDA receptor leads to a deficiency in learning in mice/ rats. 30,31 Moreover, a toluene-induced reduction of hippocampal glutamate in mice is accompanied by a poor learning performance. 32 Also in human beings, several studies suggest a link between decreased glutamatergic neurotransmission and hippocampal functions.…”