Spatial memory dissociations in mice lacking GluR1

Abstract

Gene-targeted mice lacking the AMPA receptor subunit GluR1 (GluR-A) have deficits in hippocampal CA3-CA1 long-term potentiation. We now report that they showed normal spatial reference learning and memory, both on the hidden platform watermaze task and on an appetitively motivated Y-maze task. In contrast, they showed a specific spatial working memory impairment during tests of non-matching to place on both the Y-maze and an elevated T-maze. In addition, successful watermaze and Y-maze reference memory performance depended on hippocampal function in both wild-type and mutant mice; bilateral hippocampal lesions profoundly impaired performance on both tasks, to a similar extent in both groups. These results suggest that different forms of hippocampus-dependent spatial memory involve different aspects of neural processing within the hippocampus.

A Within-Subjects, Within-Task Demonstration of Intact Spatial Reference Memory and Impaired Spatial Working Memory in Glutamate Receptor-A-Deficient Mice

“…The aim of the present study was to simultaneously assess spatial WM and RM in GluRA Ϫ/Ϫ mice, using a radial-arm maze task in which the same three of six arms are always baited, but in which the food rewards are not replaced within a trial. Whereas previously we demonstrated a clear dissociation between spatial WM and RM using different behavioral tests conducted separately at different times and in different spatial environments with different spatial cues (Reisel et al, 2002), the present experiments allow WM and RM components of spatial learning to be dissociated not only within subjects but also within the same trial. Importantly, the WM and RM components of the task are assessed using identical spatial cues.…”

“…For example, Zamanillo et al (1999) showed that gene-targeted mice lacking the AMPA receptor subunit glutamate receptor-A (GluRA) (GluR1) demonstrated normal acquisition of a spatial reference memory (RM) water maze task, despite an absence of hippocampal LTP at CA33 CA1 synapses. More recently, Reisel et al (2002) have shown that, although water maze acquisition is normal in these GluRA Ϫ/Ϫ mice, they are dramatically impaired during discretetrial, rewarded alternation on the elevated T-maze, another hippocampus-dependent memory task. This has led us to suggest that GluRA-dependent forms of synaptic plasticity may be required for spatial working memory (WM) (e.g., T-maze), but that GluRA-independent mechanisms in the hippocampus may be sufficient to support spatial RM (e.g., water maze).…”

Mice lacking the AMPA GluR1 receptor exhibit striatal hyperdopaminergia and ‘schizophrenia-related’ behaviors

“…As such, these data build upon an elegant series of studies demonstrating selective performance deficits on tests for working memory and cognitive flexibility, behaviors that are also impaired in schizophrenia. [30][31][32][33] Pharmacological blockade of NMDA receptor function with non-selective NMDA antagonist such as phencyclidine and ketamine can induce temporary psychosis in normal human subjects and provoke symptoms in schizophrenics. 51 GluR1 KO have been found to exhibit a loss of NMDA receptor-mediated long-term potentiation, but normal NMDA-receptorinduced Ca 2 þ influx and NR1 expression, in CA1 hippocampal neurons.…”

“…[24][25][26][27][28][29] Previous studies have demonstrated that GluR1 knockout mice (KO) 30 exhibit behavioral abnormalities on tests for cognition, motor function and responses to drugs of abuse. [30][31][32][33][34][35][36][37] In the present study, we sought to extend these data by assessing these mice for a variety of 'schizophrenia-related' phenotypes. In addition, given the wealth of evidence implicating dysfunction of dopamine (DA) neurotransmission in schizophrenia 2 and the major interaction between the dopamine and glutamate systems, 2,38 we evaluated regulation of extracellular striatal DA in GluR1 KO in vivo using high-speed chronoamperometry.…”

Aniracetam Reversed Learning and Memory Deficits Following Prenatal Ethanol Exposure by Modulating Functions of Synaptic AMPA Receptors

“…The fast glutamatergic neurotransmission in the mammalian brain is mediated mainly via AMPA (a-amino-3 hydro-5 methyl-isoxazole propionic acid) receptors, and their regulated activity is critical for normal synaptic transmission and specialized cognitive functions. The impairment of AMPA receptor-mediated glutamatergic transmission can result in cognitive deficits (Reisel et al, 2002), and the hippocampal AMPA receptor activation is necessary for the process of memory consolidation and retention (Yoshihara and Ichitani, 2004).…”