The neurobiology of startle
Introduction
Startle is a fast twitch of facial and body muscles evoked by a sudden and intense tactile, visual or acoustic stimulus. The startle pattern consists of eyelid-closure and a contraction of facial, neck and skeletal muscles (Fig. 1), as well as an arrest of ongoing behaviors and an acceleration of the heart rate. This response pattern is suggestive of a protective function of startle against injury from a predator or from a blow, and of the preparation of a flight/fight response. Startle can be elicited by acoustic, tactile and visual stimuli in a variety of animal species and in humans (Landis and Hunt, 1939). In addition, olfactory startle has been found in fish (Pfeiffer, 1962). Despite its relatively simple, reflex-like appearance, the startle response magnitude can be modulated by a variety of external and internal variables. That is to say, under appropriate experimental conditions, startle has a non-zero baseline and can be enhanced and attenuated. Therefore, it serves as a valuable behavioral tool to assess mechanisms of sensorimotor response plasticity. Fig. 2 summarizes the most commonly investigated phenomena of startle plasticity. By far the greatest amount of data on the neurobiology of startle has been gathered on the acoustic startle response (ASR) of mammals, mostly of rats, mice, cats and of humans. The ASR can be elicited in rats and humans using identical stimulus parameters to generate equal response patterns. The results obtained in studies with animals have repeatedly been generalized to humans, which implies that research into the neuronal mechanisms underlying the ASR and its various forms of plasticity in rats may help to understand human sensorimotor integration. This article summarizes recent findings related to the neuronal and neurochemical mechanisms mediating and modulating the ASR.
The ASR becomes functional immediately after the onset of hearing, which is around postnatal day 12 in rats (Sheets et al., 1988; Kungel et al., 1996). The ASR magnitude and latency are influenced by the stimulus intensity (Pilz et al., 1987, Pilz et al., 1988), the interstimulus interval (Davis, 1970), ongoing motor behavior (Wecker and Ison, 1986; Plappert et al., 1993), and is variable among individuals (Plappert et al., 1993). It is also influenced by genetic differences (Glowa and Carl, 1994; Paylor and Crawley, 1997), by the diurnal rhythm (Davis and Sollberger, 1971; Chabot and Taylor, 1992), by the sensory environment [e.g. background noise: Hoffman and Fleshler (1963); illumination: Walker and Davis (1997b); prepulses: Reijmers and Peeters (1994); Hoffman and Ison (1980)] and by drugs (Davis, 1980). The ASR is also modulated by a variety of experimental changes in the perceptual or emotional state of the organism: the ASR magnitude can be enhanced by conditioned and unconditioned aversive events (Davis, 1996; Davis et al., 1997). It can be attenuated by the repeated presentation of startling stimuli [habituation; Davis and File (1984)], by prior presentation of a prepulse [prepulse inhibition (PPI) and latency facilitation; Hoffman and Ison (1980)] or by positive affect (Lang et al., 1990; Schmid et al., 1995). The changes in magnitude of the ASR by systemical or intracerebral application of drugs have been widely used to assess the respective drug effects on sensorimotor reactivity in animals and humans (Davis, 1980; Davis et al., 1993). Briefly, anxiogenic drugs, for example yohimbine (Morgan III et al., 1993; Fendt et al., 1994a), and drugs that reduce the inhibitory neurotransmission in the CNS, for example, the glycine receptor antagonist strychnine (Kehne and Davis, 1984; Koch and Friauf, 1995), enhance the ASR, whereas drugs that reduce overall excitability of the CNS, such as ethanol or diazepam attenuate the ASR (Berg and Davis, 1984; Grillon et al., 1994a). Most anxiolytic drugs reduce only the fear- or anxiety-enhanced ASR and have no effect on the baseline ASR magnitude (Davis et al., 1993; Hijzen et al., 1995; Walker and Davis, 1997a). These various forms of modulation of the ASR magnitude are probably due to an enhancement or an inhibition, respectively, of the information transfer between the sensory receptors and the motor effector systems and, hence, knowledge of the pathway that mediates the ASR is a necessary prerequisite for the understanding of the modulation of the ASR.
Section snippets
A hypothetical neuronal circuit mediating the ASR
The ASR is elicited by acoustic stimuli with an intensity >80 dB sound pressure level (SPL) and a steep rise time (Davis, 1984; Pilz et al., 1987). The ASR has a short latency of ca 10 msec measured electromyographically in neck- or limb muscles (Caeser et al., 1989; Cassella et al., 1986) and is mediated by a pathway located in the ponto-medullary brainstem that has been extensively studied in rats [Davis et al. (1982a); Davis (1984); Frankland et al. (1995); Lee et al. (1996); Leitner et al.
Enhancement of the ASR
Because startle can be regarded as a protective response, it is intuitively expected that the ASR should be enhanced in threatening situations or following an aversive event. In fact, the ASR of rats has consistently found to be enhanced in the presence of a cue predicting an aversive event [fear-potentiated startle, see e.g. Davis et al. (1993)], as well as during presentation of loud noise (Davis, 1974; Gerrard and Ison, 1990; Schanbacher et al., 1996), or bright illumination (Walker and
Habituation
Habituation is a theoretical construct referring to the reduction in magnitude of the ASR after repeated presentation of the startling stimulus that is not due to muscle fatigue or blunting of sensory receptor responsiveness (Davis and File, 1984; Christoffersen, 1997). Within-session, or short-term habituation, that is, the decline of the ASR magnitude following repeated presentation of startling stimuli within a single test session [Fig. 2(C)Fig. 8] is distinguished from between-session
Conclusion
The ASR is a simple reflex-like behavior that can be reliably elicited and exactly quantified in a variety of experimental animals and in humans. It is mediated by a relatively simple oligosynaptic pathway located in the pontine brainstem and is modulated by perceptual (prepulses) and state (positive or negative affect) variables and by a variety of drugs. Hence, the ASR can be used as a behavioral tool to assess brain mechanisms of sensorimotor integration in mammals. The PnC is one of the key
Acknowledgements
The author's work is supported by the Deutsche Forschungsgemeinschaft (SFB 307; SPP 1001 and Heisenberg Programm). The author thanks Drs M. Bubser, M. Davis, U. Ebert, E. Friauf, W. Hauber, H. Herbert, B. Kretschmer, M. Kungel, P. Lang, R. Leaton, K. Lingenhöhl, J. Ostwald, P. Pilz, C. Plappert, H-U. Schnitzler, N. Swerdlow, T. Wagner and J. Yeomans for many fruitful discussions and collaborations. He gratefully acknowledges the enthusiastic collaboration of his students Dr M. Fendt, K. Japha,
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