Autonomic function in mice during aversive emotional behavior tests

O. Stiedl¹ and M. Meyer²

¹Department of Developmental and Behavioural Neurobiology and Department of Functional Genomics, CNCR and INW, Vrije Universiteit Amsterdam, The Netherlands
²Fractal Physiology Group, Max Planck Institute for Experimental Medicine, Göttingen, Germany

The determination of autonomic function, i.e. sympatho-vagal interaction, has been introduced to supplement traditional behavioral measures during fear conditioning, an emotional learning paradigm in many species including mice. This paradigm is used to investigate the dynamics of heart rate and blood pressure in mice in order to determine three major aspects:

1. Physiological adjustments.
2. Pharmacological modulation.
3. Genetic approaches using mutant mice to investigate the contribution of specific neuropeptides to physiological cardiovascular conditions.

The understanding of physiological characteristics is mandatory to draw proper conclusions as to the effects of pharmacological interventions on retention or expression of aversive memories. Furthermore, autonomic measures allow for stress-free behavioral tests in the home cage of mice when conventional behavioral parameters are unreliable. The normal heart rate displays complex fluctuations in time in response to environmental factors (breathing, activity, emotion), all of which are mediated by different central and peripheral feedback loops acting in parallel over a wide range of time scales. Measures of sympatho-vagal balance derived from non-linear analysis of heart rate variability re.ect a highly dynamical function, the homeodynamics of which being accessible by advanced analytical techniques. Analysis of heart rate dynamics by techniques derived from statistical physics facilitates a translational approach from mouse to man. The methods are useful to uncover physiological principles and their pathological alterations, and hence, allow for assessment of cardiac risk in both man and mouse irrespective of species-speci.c differences in absolute heart rate. We hypothesize that:

1. Central autonomic dysregulation may contribute to elevated cardiac risk in the absence of genuine heart disease,
2. Autonomic dysregulation is potentially linked to the enhanced incidence of adverse cardiac events observed in epidemiological studies of psychopathological disorders in humans.

With the implementation of autonomic measures, mouse models of chronic stress or depression will be investigated.

Paper presented at Measuring Behavior 2005 , 5^th International Conference on Methods and Techniques in Behavioral Research, 30 August - 2 September 2005, Wageningen, The Netherlands.

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