UniversitΣt Tⁿbingen - Lehrstuhl Tierphysiologie

Arbeitsgruppe Sensomotorische Integration

-Publikationen-

Pleasure-attenuated startle

Annette Schmid, Michael Koch , Hans-Ulrich Schnitzler:
Conditioned pleasure attenuates the startle response in rats

in: Neurobiol. Learning Memory, (1995) 64:1-3

Abstract:
The acoustic startle response of rats was found to be attenuated if elicited in the presence of a conditioned stimulus predicting reward. During conditioning, animals received a total of twenty one pairings of light with palatable food and sucrose solution, whereas controls received food and sucrose in the absence of light. The amplitude of the acoustic startle response was significantly reduced in the presence of light in conditioned animals, but not in controls. It is assumed that a conditioned response to light is the activation of a central state of pleasure. We therefore suggest that 'pleasure-attenuated startle' reflects a mechanism by which a defensive or aversive response is attenuated during a pleasant, hedonic state.

Neural mechanismsof pleasure-attenuated startle

Michael Koch, Annette Schmid Hans-Ulrich Schnitzler:
Pleasure-attenuation of startle is disrupted by lesions of the nucleus accumbens

in: Neuroreport (1996) 7:1442-1446

Abstract:
The nucleus accumbens (NAC) and the amygdala have been implicated in processes by which reinforcers control instrumental behavior. Since reinforcement has both motivational and motor components, it is necessary to differentiate between these two aspects of reinforcement. The acoustic startle response (ASR) is attenuated in the presence of a secondary reinforcer. In contrast to other paradigms used for investigating mechanisms of reward, the "pleasure-attenuated-startle" (PAS) paradigm indicates the rewarding properties of a treatment by an attenuation rather than by reinforcement of a response, thus allowing to determine the motivational impact of a treatment independent from its motor stimulating effects. Here, we report that the ASR was attenuated in the presence of a reinforcer in conditioned sham-operated animals and in rats with lesions of the amygdala, but not in animals bearing 6-hydroxydopamine lesions of the NAC. These findings suggest that the catecholaminergic innervation of the NAC is important for the behavioral control by conditioned reward

Noise facilitation, startle and amygdala

Annette Schanbacher , Michael Koch, Hans-Ulrich Schnitzler:
Lesions of the amygdala do not affect the enhancement of the acoustic startle response by background noise

in: Physiol. Behav.(1996) 60:1341-1346

Abstract:
The acoustic startle response (ASR) is enhanced in the presence of loud background noise. We examined whether or not this increase of response strength is mediated by the amygdala, which is known to be involved in various phenomena of enhancement of the ASR. To achieve this aim, we tested whether or not amygdaloid lesions with the excitotoxin N-methyl-D-aspartate (NMDA) would abolish the enhancement of the ASR by background noise in 13 Wistar rats. Loss of foot shock sensitization in these rats, as well as histological evaluation, proved the successful destruction of the amygdala. However, the enhancement by background noise of the ASR, which was observed in sham-operated controls, was not affected in amygdala-lesioned rats. Therefore, we conclude that the background noise facilitation does not involve emotional components that are mediated by the amygdala. On the basis of these findings, we differentiate between the startle-enhancing effect of background noise and the amygdala-mediated effect of foot shocks on the ASR.

Somatostatin modulates fear-potentiated startle

Markus Fendt , Michael Koch, Hans-Ulrich Schnitzler:
Somatostatin in the pontine reticular formation modulates fear-potentiation of the acoustic startle response: An anatomical, electrophysiological and behavioral study

in: J. Neurosci. (1996) 16:3097-3103

Abstract:
The amplitude of the acoustic startle response (ASR) in rats is increased in the presence of a cue which has previously been paired with an aversive stimulus such as a footshock. This phenomenon is called fear-potentiated startle and is a model to study the neuronal and neurochemical mechanisms of the acquisition and expression of fear.

The present study investigated the role in fear-potentiated startle of somatostatin (SOM) in the caudal pontine reticular nucleus (PnC) by a combination of anatomical, electrophysiological and behavioral methods. The PnC is an essential part of the primary startle circuit and is also the recipient of modulatory influences. First, we showed that the central gray (CG), which is involved in fear conditioning, is the main source of SOM-somatostatinergic input to the PnC. In the second experiment, we iontophoretically applied the SOM-somatostatin receptor agonist sandostatin on PnC neurons and extracellularly recorded the activity of PnC neurons. Sandostatin had no effect on tone-tone-evoked or spontaneous activity, but markedly attenuated the increase of neuronal activity seen after the administration of glutamate. In our third experiment, we injected different doses of sandostatin into the PnC of awake rats. Sandostatin dose-dependently blocked the fear-potentiation of the ASR, but had no effect on the baseline ASR amplitude.

The present study indicates that the SOM-somatostatinergic projection from the CG to the PnC is important for the modulation of fear-potentiated startle. We present a possible neural circuitry for the expression of fear-potentiated startle based on these data and previous findings.

Superior colliculus and sensorimotor gating

Markus Fendt Michael Koch, Hans-Ulrich Schnitzler:
Sensorimotor gating deficit after lesions of the superior colliculus

in: NeuroReport (1994) 5:1725-1728

Abstract:
The superior colliculus (SC) is important for the processing of sensory information of different modalities and for the mediation of adequate motor responses in mammals. The present study investigated the effects of excitotoxic lesions of the SC on two different modulations of the acoustic startle response (ASR) in rats. Modulations of the ASR (i. e. increase or decrease of the response strength) represent useful models for the study of sensorimotor integration phenomena. Lesions of the SC decreased the prepulse inhibition of the ASR without affecting the baseline startle amplitude or the enhancement of the ASR by footshock-sensitization. These results suggest a crucial role of the SC in the prepulse inhibition of the ASR, a model of sensorimotor gating.

Central gray and sensitization

Markus Fendt, Michael Koch, Hans-Ulrich Schnitzler:
Lesions of the central gray block conditioned fear as measured with the potentiated startle paradigm

in: Brain Res. (1994) 661:163-173

Abstract: The amplitude of the acoustic startle response (ASR) in rats is increased in the presence of a cue which has previously been paired with an electric footshock. This phenomenon is termed fear-potentiated startle and is a useful model to investigate the neural systems underlying fear and anxiety. A series of studies have shown, that the amygdaloid complex is necessary for the acquisition and the expression of conditioned fear. Further experiments have delineated an efferent amygdalofugal pathway to the primary startle circuit, at the level of the caudal pontine reticular formation, which mediates the expression of conditioned fear [10]. Yet it was unclear, whether this amygdaloreticular pathway directly transfers the effects of conditioned fear from the amygdala to the primary startle circuit, or whether there exist one or more relay nuclei within this pathway or even additional parallel circuits. Based on our previous finding that the midbrain central gray (CG) is involved in the mediation of the facilitatory effects on the ASR of unconditioned aversive events, the present study tested the hypothesis that the CG is important for the potentiation of the ASR by conditioned fear. Therefore, we lesioned the CG before and after fear-conditioning and examined the effects of these lesions on fear-potentiated startle. Pre- and post-training lesions of the CG totally blocked the potentiation of the ASR amplitude by conditioned fear, which was seen in sham-lesioned rats, indicating that CG lesions affected the expression of conditioned fear. The baseline ASR amplitude was not influenced by CG lesions. We discuss possible pathways and mechanisms underlying the expression of conditioned and unconditioned fear in rats.

CRF modulates fear-potentiated startle

Markus Fendt , Michael Koch, Hans-Ulrich Schnitzler:
Corticotropin-releasing factor in the caudal pontine reticular nucleus regulates the expression of fear-potentiated startle

in: Eu. J. Neurosci. (1997) 9:299-305

Abstract:
The neuronal basis of the expression of states of fear is still not completely understood. The fear-potentiated startle paradigm is a valuable model to investigate the neuronal basis of fear. Previous studies have demonstrated that the neuropeptide corticotropin-releasing factor (CRF) plays an important role in fear-related processes, notably in the potentiation of the acoustic startle response. The present study investigated the role in fear-potentiated startle of CRF in the caudal pontine reticular nucleus, a brain nucleus that mediates the acoustic startle response. A combination of anatomical, electrophysiological and behavioural methods was applied. First, we could show that the central nucleus of the amygdala gives rise to a CRF-ergic projection to the caudal pontine reticular nucleus. In the second experiment, we iontophoretically applied CRF on caudal pontine reticular nucleus neurones and extracellularly recorded the activity of these neurones. CRF had a mainly excitatory effect on the tone-evoked activity of caudal pontine reticular nucleus neurones. In our third experiment, we injected the CRF antagonist a -helical CRF into the caudal pontine reticular nucleus of awake rats. Here, a -helical CRF dose-dependently blocked fear-potentiated startle, but had no effect on the baseline startle amplitude. The present results further characterise the hypothetical neuronal circuitry underlying the expression of fear-potentiated startle

Central gray and fear-potentiated startle

Markus Fendt , Michael Koch, Hans-Ulrich Schnitzler:
Lesions of the central gray block the sensitization of the acoustic startle response in rats

in: Behav. Brain Res. (1996) 74:127-134

Abstract:
The amplitude of the acoustic startle response (ASR) in rats is increased after administration of footshocks, a phenomenon termed sensitization. The neural circuitry underlying this kind of modulation of the ASR is only partly understood. It has been shown that the central nucleus of the amygdala (cA) and its efferent pathway to the caudal pontine reticular nucleus (PnC), an essential part of the primary startle circuit, is important for the sensitization of the ASR [23]. It was unclear, however, whether the amygdaloreticular pathway directly transfers the effects of footshocks onto the PnC, or whether there exists a relay nucleus within this pathway. The present study tested the hypothesis that the midbrain central gray (CG) is important for the sensitization of the ASR. Neuroanatomical tracing experiments indicate that a descending projection from the medial part of the cA might form synapses in the region of the midbrain CG, where a descending projection to the PnC takes its origin. We lesioned the dorsal and lateral part of the CG with the neurotoxin quinolinic acid and measured the effects of this lesion on the sensitization of the ASR by footshocks. Lesions confined to the dorsal and lateral parts of the CG totally blocked the sensitization of the ASR, without affecting the ASR amplitude in the absence of sensitizing stimuli. These findings suggest a crucial role of the CG for the sensitization of the ASR. The present data are reconciled with other findings from our laboratory and from the literature and we discuss possible mechanisms underlying the mediation of the sensitization of the ASR in rats

CCK and startle

Markus Fendt , Martin Kungel, Michael Koch, Hans-Ulrich Schnitzler:
Cholecystokinin enhances the acoustic startle response in rats

in: NeuroReport (1995) 6:2081-2084

Abstract:
The present study examined the effects of the neuropeptide cholecystokinin (CCK) on neurons of the caudal pontine reticular nucleus (PnC), which mediates the acoustic startle response (ASR) in rats. Electrophysiological experiments revealed an excitatory effect of CCK on acoustically responsive neurons in the PnC. On the behavioral level, CCK also enhanced the ASR. Since the PnC is not only an obligatory relay station of the brain circuit mediating the ASR, but also receives modulatory input from brain areas involved in the expression of fear and anxiety, the enhancement of the ASR by CCK could be interpreted as an anxiogenic-like effect of this peptide.

Amygdala, Noradrenaline and Startle

Markus Fendt, Michael Koch Hans-Ulrich Schnitzler:
Amygdaloid noradrenaline is involved in the sensitization of the acoustic startle response in rats

in: Pharmacol. Biochem. Behav. (1993) 48:307-314

Abstract:
The present study examined the role of noradrenaline (NA) in the central nucleus of the amygdala (cA) in the sensitization of the acoustic startle response (ASR) in rats. In the first experiment local microinjections of 0, 0.5, 1, 2 nmol of the a 2-adrenergic antagonist yohimbine into the cA increased the magnitude of the ASR in a dose-dependent way. In the second experiment footshocks were applied in order to increase the ASR amplitude (sensitization). Local microinjections of 0, 4, 8, 16 nmol of the a 2-adrenergic agonist ST-91 into the cA dose-dependently decreased the sensitizing effects of footshocks on the amplitude of the ASR. It is conjectured that yohimbine increases, and ST-91 decreases local NA-release by acting at presynaptic autoreceptors. The present data suggest that the release of NA in the cA is involved in the mediation of the sensitizing effects of footshocks on the ASR.

Glutamat and fear-potentiated startle

Markus Fendt , Michael Koch, Hans-Ulrich Schnitzler:
NMDA receptors in the pontine brainstem are necessary for fear-potentiation of the startle response

in: Eu. J. Pharmacol. (1996) 318:1-6

Abstract:
The fear-potentiated startle paradigm in rats is a valuable animal model for the investigation of the neural and neurochemical basis of fear. In this model, rats are trained to associate a neutral stimulus with an aversive stimulus, so that after conditioning the CS alone elicits a state of fear leading to an exaggerated acoustic startle response (ASR). The fear-potentiated startle paradigm does not require instrumental responding for the indication of states of fear. The ASR is mediated by a simple brainstem circuit, with the caudal pontine reticular nucleus (PnC) as an interface that receives input from startle-enhancing circuits. In the present study, we tested the hypothesis that NMDA receptors on PnC neurones are involved in the mediation of fear-potentiated startle. After fear-conditioning, we injected the NMDA receptor antagonist DL-2-amino-5-phosponopentanoic acid (AP-5) into the PnC of awake rats and tested the effect on the expression of fear-potentiated startle. Injections of AP-5 (0.125 - 0.5 nmol) into the PnC dose-dependently attenuated fear-potentiated startle without affecting the baseline ASR amplitude. The results suggests that, at the level of the PnC, glutamate may mediate fear-potentiated startle via NMDA receptors.

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