The role of the GluR−A (GluR1) AMPA receptor subunit in learning and memory

School of Psychology, Cardiff University, Tower Building, Park Place, PO Box 901, Cardiff, CF10 3YG, UK
Progress in brain research (Impact Factor: 5.1). 01/2008; 169.
Source: OAI

ABSTRACT It is widely believed that synaptic plasticity may provide the neural mechanism that underlies certain kinds of learning and memory in the mammalian brain. The expression of long−term potentiation (LTP) in the hippocampus, an experimental model of synaptic plasticity, requires the GluR−A subunit of the AMPA subtype of glutamate receptor. Genetically modified mice lacking the GluR−A subunit show normal acquisition of the standard, fixed−location, hidden−platform watermaze task, a spatial reference memory task that requires the hippocampus. In contrast, these mice are dramatically impaired on hippocampus−dependent, spatial working memory tasks, in which the spatial response of the animal is dependent on information in short−term memory. Taken together, these results argue for two distinct and independent spatial information processing mechanisms: (i) a GluR−A−independent associative learning mechanism through which a particular spatial response is gradually or incrementally strengthened, and which presumably underlies the acquisition of the classic watermaze paradigm and (ii) a GluR−A−dependent, non−associative, short−term memory trace which determines performance on spatial working memory tasks. These results are discussed in terms of Wagner's SOP model (1981).

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    • "The primary aim of this study, therefore, was to evaluate the effect of OLZ and HAL on hippocampal-dependent memorial deficits (e.g., spatial learning and memory, as well as spatial working memory) usually observed in schizophrenia (Hanlon et al., 2011; Henseler et al., 2009; Wood et al., 2002) and to investigate the underlying neuroplasticity mechanism behind this discrepancy. It is known that the expression of LTP in the hippocampus requires the GluR1 subunit of the AMPA subtype of glutamate receptor (Sanderson et al., 2008). Oh et al. (2006) reported that GluR1 Ser845 phosphorylation can prime AMPA receptors for LTP; thus, as a secondary aim, we quantified the effect of OLZ and HAL on the state of Ser845 phosphorylation of GluR1 in the hippocampus. "
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    • "By PND 30-32 mice show hippocampus dependent and hippocampus independent deficits while hyper-locomotion cannot be clearly seen and no double dissociation is possible since the poorer cognitive abilities may, theoretically, affect investigation (Sanderson et al., 2008). "
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    • "In a typical working memory procedure, the organism must hold information online for a short period of time in order to successfully complete a goal-oriented task, such as the spatial information connected to the location of a food reward that enables maze navigation after a delay. The PFC (Goldman-Rakic, 1995) and the hippocampus (Sanderson et al., 2008) each participate in working memory function. Direct evidence demonstrating that these brain structures functionally interact during working memory has come from rodent experiments involving asymmetric pathway disconnection methods (also called ''crossed lesions''). "
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