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San Diego,
November 2001
(also presented
at Irvine, November 2001)
LTP-Deficient GluR1-/- Mice Are Unimpaired on a Hippocampal-Dependent
Spatial Reference Memory Task
Reisel1, D., Schmitt1, W., Kirby1, B.P., Sprengel2, R., Andersen3, P.,
Seeburg2, P.H. Sakmann2, B., Deacon1, R.M.J., Bannerman1, D.M., Rawlins1,
J.N.P. 1Department of Experimental Psychology, University of Oxford,
Oxford, UK; 2Max-Planck Institute for Medical Research, Heidelberg,
Germany; 3Department of Physiology, University of Oslo, Norway.
L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) GluR-A
receptor subunit activity is widely regarded as underlying the consolidation
of long term potentiation (LTP). LTP-like changes in synaptic efficacy
in the hippocampal formation are thought to support certain types of
learning and memory. However, GluR-A -/- mice lacking LTP in the CA1
to CA3 region are not impaired on the spatial version of the Morris
water maze1.
The present
study attempts to ascertain whether this lack of impairment is specific
to the aversively motivated water maze or whether it extends to other
tests of spatial reference memory. First, we demonstrated that cytotoxic
hippocampal lesions inhibit learning of an appetitively motivated Y-maze
spatial reference memory task. The task proved highly sensitive to hippocampal
damage, eliciting a statistically significant difference between the
two groups. (F(1,21)=69.65; p>0.0001). We then compared wild type
and GluR-A -/- mice on the same task. By contrast, we found no significant
difference between the groups (F<1; p>0.50).
These results
indicate that the initial conclusions regarding the behaviour of the
LTP-deficient GluR-
A -/- mice in the Morris water maze can be extended to the Y-maze. Similarly
to the water maze, this task relies on the ability to learn and retain
spatial information, yet it differs in terms of sensorimotor and motivational
demands.
1. Zamanillo,
D., et al. (1999) Science 284: 1805-1811.
Eilat, December
2001
Dissociation
of Working and Reference Memory in TP-Deficient GluR1-/- Mice
Reisel D.1, Schmitt W.1, Andersen P.3, Seeburg P.H.2, Sakmann B.2, Sprengel
R.2, Deacon R.M.J.1, Bannerman D.M.1, Rawlins J.N.P.1 1Department of
Experimental Psychology, University of Oxford, UK; 2Max-Planck Institute
for Medical Research, University of Heidelberg, Germany; 3Department
of Physiology, University of Oslo, Norway.
L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor
activity is required for long-term potentiation (LTP), a postulated
model of cellular mechanisms underlying learning and memory. GluR1 (GluR-A),
one of four AMPA receptor subtypes, is thought to mediate a postsynaptic
mechanism of LTP expression. Previous studies have demonstrated that
GluR1-deficient mice lack LTP in the afferent pathways to the CA1 area
of the hippocampus, yet their spatial reference memory is intact (Zamanillo
et al, Science 284:1805-1811 [1999]). The present
study investigated the role of AMPA GluR1 in working memory. Using male
GluR1-/- mice, we examined the functional significance of this receptor
subtype in a rewarded alternation task on the elevated T-maze, a measure
of spatial working memory. Performance on the T-maze was dramatically
impaired by GluR1 deletion (wild-types: 81.0%, mutants: 50.8% F(1, 26)=58.4;
p<0.0001). We then tested the same GluR1-/- mice on the standard
version of the Morris water maze task, a measure of spatial reference
memory. In agreement with the previous study, performance in the Morris
water maze was unimpaired; there was no difference between GluR1-/-
mice and controls on a probe test with the hidden platform removed (wild-types:
44.6%, mutants: 46.9% F<1; p>0.2). These results support an important
role for AMPA GluR1 in spatial working memory but not in spatial reference
memory.
Keywords:
AMPA, GluR1 (GluR-A), working memory.
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