Analysing hippocampal function in transgenic mice: an ethological perspective

doi:10.1016/S0166-2236(98)01346-0

Trends in Neurosciences

Volume 22, Issue 2, 1 February 1999, Pages 47-51

https://doi.org/10.1016/S0166-2236(98)01346-0 Get rights and content

Abstract

Advances in molecular genetics and transgenic technology have led to the dawn of a new era for neuroscience: manipulation of single genes now makes it possible to dissect the complexities of neurobiological phenotypes and to understand many of the intricacies of brain and behaviour, even in mammals. The phenotypical analysis of these mutant animals is complicated because the potential outcome of gene manipulation is difficult to predict. While behavioural analysis should form an integral part of any multidisciplinary research programme investigating the phenotypical effects of single genes on hippocampal function, it is crucial that the behavioural tests are designed and conducted appropriately. Approaches that take species-specific behavioural characteristics into account and use ethological methods could be the most useful for interpreting these behavioural findings and understanding the biological mechanisms of brain function.

Section snippets

Behavioural analysis could reveal abnormal brain function

Of the many approaches used to analyse phenotypical effects of mutations on brain function2, 3, 4, 5, behavioural analysis is perhaps the most tricky: experiments appear easy to execute and quantitative data can be collected quickly, yet there are several difficulties associated with analysing the behavioural effects of a mutation on hippocampal function. An obvious problem is that some basic performance factors can influence behavioral results. For example, a mouse with a motor impairment

The importance of designing ethologically relevant behavioural tasks

In the laboratory, animals can behave in ways that are difficult to interpret, partly because they are genetically predisposed to selectively attend to, process and recall certain specific stimuli that might be altered under artificial conditions. Early examples that showed the importance of designing ethologically relevant tasks came from studies of learning in rats. For example, rats learned classical-conditioning-avoidance tasks quickly when food was associated with nausea-inducing

Species-specific characteristics of behaviour

Differences in learning abilities between species are inevitable because each species faces different problems in nature. As Kamil and Maudlin indicate, ‘The effects of a learning procedure upon a species will depend on how the learning paradigm makes contact with the adaptations and response repertoire of the animal’¹⁰. Consider the performance of various rodent species that have been tested on the Morris water maze, a spatial- and relational-learning task originally designed for rats that

Designing the right task for the right species

Understanding of the species' natural history would allow the experimenter to design an ethologically appropriate task by predicting what sort of motor responses might occur, what kind of stimuli the experimental subjects were more sensitive to and what type of cognitive constraints characterized their learning abilities. There are numerous examples of species specificity in motor responses and the salience of associating the appropriate stimulus and response, for example, rats learn to

Factors that affect exploratory behaviour

The common feature of spatial learning tests applied in recent studies of the molecular neurobiology of learning, apart from the fact that they were intended to reveal hippocampal dysfunction, is that they represent novel situations in which exploratory behaviour is evoked. Exploratory behaviour, however, is a complex response to novelty that results from a compromise between the motivation to gather information about the surroundings and the need to avoid predators28, 29. Laboratory conditions

The advantage of combining field and laboratory studies

Throughout this review, the importance of considering the natural behaviour of the animal when designing behavioural tests has been emphasized. In order to design ethologically appropriate tests for the species in question, information is needed about how these animals perform under naturalistic conditions. Surprisingly, it is only very recently that such an approach has been adopted to study hippocampal function in rodents in their natural environment38, 39. It would be illuminating to

Concluding remarks

Although it is tempting to employ a general behavioural assay for investigating phenotypical changes that a single-gene manipulation might have caused, the studies cited above demonstrate that we need to consider the ethological relevance of the tasks for the species in question and that we might need to modify existing tests or design new ones, depending on the question asked and the genetic manipulation that we employ. While the importance of using ethologically relevant tasks does not imply

Acknowledgements

We thank Pam Banta, Wim Crusio, Tony Dickinson, Dan Griffiths, Martin Kavaliers, Sandra Kelly, Pierre Lavenex and Stephen Maxson for their useful comments on an earlier version of this review and Kevin Ling for video processing. Financial support for our research comes from GENENTECH (to R.G.) and NIH, Whitehall Foundation, AFAR and NIA (to N.S.C.).

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Trends in Neurosciences

ViewpointAnalysing hippocampal function in transgenic mice: an ethological perspective

Abstract

Section snippets

Behavioural analysis could reveal abnormal brain function

The importance of designing ethologically relevant behavioural tasks

Species-specific characteristics of behaviour

Designing the right task for the right species

Factors that affect exploratory behaviour

The advantage of combining field and laboratory studies

Concluding remarks

Acknowledgements

Cell

Semin. Neurosci.

J. Neurosci. Methods

Brain Res.

Anim. Behav.

Learn. Motiv.

J. Neurol. Neurosurg. Psychiatry

Learn. Mem.

Science

Trends Neurosci.

Psychonomic Sci.

J. Neurosci.

J. Neurosci.

Behav. Brain Res.

Viewpoint
Analysing hippocampal function in transgenic mice: an ethological perspective