Research reportThe acoustic startle response in rats—circuits mediating evocation, inhibition and potentiation
Introduction
One of the most pertinent problems of behavioral neurobiology is to understand the neuronal mechanisms underlying variable stimulus-response relationships. The strength of such behaviors which are under stimulus control can be enhanced or attenuated despite constant stimulus conditions, depending upon the internal state of the organism (motivation, attention, arousal) and/or acute environmental demands. A paradigmatic animal model applied to study behavioral plasticity was the gill withdrawal reflex investigated in the marine mollusc Aplysia [58]. Yet, comparably successful models are very rare in mammalian species, which is probably due to the fact that most mammalian behaviors are mediated by complicated polyneuronal pathways.
The present review attempts to demonstrate that the acoustic startle response (ASR) in rats is a useful model for the study of the plasticity of sensorimotor information processing in mammals. We here summarize the current knowledge about the brain mechanisms that mediate and modulate the ASR in rats. The ASR is a relatively simple response, characterized by a rapid contraction of facial and skeletal muscles following an unexpected and intense acoustic stimulus. The ASR has been observed in many mammalian species, including humans [105], and probably represents a protective response, because its behavioral pattern consists of reactions that are likely to prevent severe injury from an attack, such as stiffening of the neck musculature, eyelid closure, limb flexion, and facilitation of a flight response [103].
The ASR is subject to a variety of influences which modify its response magnitude. Strain differences [41], drugs [17], the diurnal rhythm 14, 25, habituation 15, 21, 23, 56, sensitization [18], fear-potentiation [20], background noise 16, 53, 55, 116, locomotor activity 104, 137, prepulse inhibition [54]and pleasure-attenuation 73, 117are phenomena which all increase or decrease the magnitude or probability of occurrence of the ASR. The fact that the ASR is usually not changed in quality—or pattern—by these modulatory influences, but rather simply enhanced or attenuated, makes it easy to reliably quantify the effects of these modulations. Although it is of great interest to know through which neuronal mechanisms the different phenomena listed above can be explained, the physiological basis of most of these examples for response plasticity is still not completely understood. The present article advocates the view that a multidisciplinary approach, combining anatomical, physiological and behavioral techniques, is necessary to understand the neuronal basis of the ASR and its various phenomena of modulation. This approach will lead to the characterization of behaviorally relevant brain pathways and help to gain insight into the general principles of sensorimotor integration.
Section snippets
The primary startle pathway
A prerequisite for the understanding of the different kinds of modification of the ASR is the knowledge of the neuronal substrates that mediate the ASR, i.e. the primary, or elementary startle pathway. The ASR is elicited by stimuli with an amplitude of more than 80 dB above the auditory threshold of the rat [102]. Based on the observation that the latency of the ASR is very short (5–10 ms for the electromyographically measured response in different muscles) 8, 12, 13, 100, 101, it can be
Habituation
The term habituation refers to the reduction in amplitude of the startle response after repeated presentation of the startling stimulus [21]. A distinction is made between within-session, or short-term habituation (i.e. the decline of the startle response amplitude after repeated stimulation within a single test session (Fig. 3) and between-session habituation, or long-term habituation (i.e. the reduction of the startle response amplitude across several test session). Habituation can be
Prepulse inhibition
The ASR amplitude is reduced if a non-startling stimulus is presented 30–500 ms before the startle pulse occurs (Fig. 4). This phenomenon is termed prepulse inhibition (PPI) and has received considerable attention in recent years as an example of sensorimotor gating 54, 105. This kind of suppression, or gating of brain circuits that would disrupt the ongoing information processing routine that deals with the prepulse, reflects a fundamental principle of the neural control of behavior which is
Sensitization and fear-potentiation
The term sensitization refers to the observation that a response can be enhanced by activation of an additional brain system, which strengthens sensorimotor transmission by a mechanism of presynaptic facilitation [58]. Sensitization has been considered a nonassociative form of learning. However, in its strict sense the term sensitization is only applicable to a nonhabituated response, while in the case of a habituated response, dishabituation is indistinguishable from sensitization. In the
Conditioned inhibition of fear
Interestingly, recent studies from the Davis group have shown that the effects of conditioned fear in rats can be overcome through the learning of safety signals which predict the absence of shocks. The first experiments that addressed the underlying brain structures have demonstrated that the amygdala is not necessary for the suppression of fear by conditioned inhibition [28]. These recent endeavours to gain insights into the brain mechanisms which suppress fear propose new avenues of research
Pleasure-attenuation
The fact that the amplitude of the ASR is increased during states of fear both in rats and in humans (see above) lead to the concept that the strength of the ASR can be regarded as an indicator of the emotional state of an organism. Consistent with this concept, Lang and his co-workers have found that in humans the ASR is decreased if elicited in a pleasant (`hedonic') emotional context [82]. This finding has been extended to rats by demonstrating that the ASR amplitude is reduced if the ASR is
Concluding remarks
The ASR is a relatively simple protective behavior which is mediated by a well known oligosynaptic neuronal circuit located in the pontine brainstem. The application and combination of neurophysiological, neuropharmacological and neuroanatomical techniques has provided a wealth of information about the brain mechanisms which evoke and modulate the ASR. Two important phenomena of response plasticity (the enhancement of the ASR by fear and the attenuation of the ASR by prepulses) have already
Acknowledgements
The work in the author's laboratory was supported by the Deutsche Forschungsgemeinschaft (SFB 307 and SPP 1001). It would look pretty much like a roll-call to write down the names of all those who were involved in the present work, but we should like to specially thank Dr Markus Fendt and Dr Thomas Wagner who commented on the manuscript, and to Dr Peter Pilz and Dr Joachim Ostwald for helpful discussions over the years.
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