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      The role of habituation in hippocampus-dependent spatial working memory tasks: Evidence from GluA1 AMPA receptor subunit knockout mice


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          Spatial alternation, win-shift behavior has been claimed to be a test of working memory in rodents that requires active maintenance of relevant, trial-specific information. In this review, we describe work with GluA1 AMPA receptor subunit knockout mice that show impaired spatial alternation, but normal spatial reference memory. Due to their selective impairment on spatial alternation, GluA1 knockout mice provide a means by which the psychological processes underlying alternation can be examined. We now argue that the spatial alternation deficit in GluA1 knockout mice is due to an inability to show stimulus-specific, short-term habituation to recently experienced stimuli. Short-term habituation involves a temporary reduction in attention paid to recently presented stimuli, and is thus a distinct process from those that are involved in working memory in humans. We have recently demonstrated that GluA1 knockout mice show impaired short-term habituation, but, surprisingly, show enhanced long-term spatial habituation. Thus, GluA1 deletion reveals that there is competition between short-term and long-term processes in memory. © 2010 Wiley Periodicals, Inc.

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          Repetition and the brain: neural models of stimulus-specific effects.

          One of the most robust experience-related cortical dynamics is reduced neural activity when stimuli are repeated. This reduction has been linked to performance improvements due to repetition and also used to probe functional characteristics of neural populations. However, the underlying neural mechanisms are as yet unknown. Here, we consider three models that have been proposed to account for repetition-related reductions in neural activity, and evaluate them in terms of their ability to account for the main properties of this phenomenon as measured with single-cell recordings and neuroimaging techniques. We also discuss future directions for distinguishing between these models, which will be important for understanding the neural consequences of repetition and for interpreting repetition-related effects in neuroimaging data.
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            Synaptic plasticity and memory: an evaluation of the hypothesis.

            Changing the strength of connections between neurons is widely assumed to be the mechanism by which memory traces are encoded and stored in the central nervous system. In its most general form, the synaptic plasticity and memory hypothesis states that "activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the information storage underlying the type of memory mediated by the brain area in which that plasticity is observed." We outline a set of criteria by which this hypothesis can be judged and describe a range of experimental strategies used to investigate it. We review both classical and newly discovered properties of synaptic plasticity and stress the importance of the neural architecture and synaptic learning rules of the network in which it is embedded. The greater part of the article focuses on types of memory mediated by the hippocampus, amygdala, and cortex. We conclude that a wealth of data supports the notion that synaptic plasticity is necessary for learning and memory, but that little data currently supports the notion of sufficiency.
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              AMPA receptor trafficking and synaptic plasticity.

              Activity-dependent changes in synaptic function are believed to underlie the formation of memories. Two prominent examples are long-term potentiation (LTP) and long-term depression (LTD), whose mechanisms have been the subject of considerable scrutiny over the past few decades. Here we review the growing literature that supports a critical role for AMPA receptor trafficking in LTP and LTD, focusing on the roles proposed for specific AMPA receptor subunits and their interacting proteins. While much work remains to understand the molecular basis for synaptic plasticity, recent results on AMPA receptor trafficking provide a clear conceptual framework for future studies.

                Author and article information

                Wiley Subscription Services, Inc., A Wiley Company (Hoboken )
                May 2012
                01 December 2010
                : 22
                : 5
                : 981-994
                Department of Experimental Psychology, University of Oxford South Parks Road, Oxford, United Kingdom
                Author notes
                *Correspondence to: Dr. David J. Sanderson, Department of Experimental Psychology, University of Oxford, South Parks Road, Oxford, OX1 3UD, UK. E-mail: david.sanderson@ 123456psy.ox.ac.uk

                Grant sponsor: Wellcome; Grant number: 87736.

                Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms

                Copyright © 2010 Wiley Periodicals, Inc.

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.



                working memory, ampa receptors, mice, habituation, hippocampus, plasticity


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