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Decreased spontaneous motor activity and startle response in nitric oxide synthase inhibitor-treated rats.

In the central nervous system, nitric oxide has been proposed to be a retrograde messenger mediating learning and synaptic plasticity. Since only pretraining injections of nitric oxide synthesis inhibitors were shown to impair learning, we examined the possibility that systemic administration of these inhibitors might influence some non-specific aspects related to the organism's general psychophysiological status. Intraperitoneal administration of NG-nitro-L-arginine methyl ester (30 or 100 mg/kg) 60 min pre-test to adult rats resulted in: (i) altered exploratory pattern and reduced locomotion in a novel environment; (ii) reduced startle response to either acoustic or electric stimuli; and (iii) cardiovascular alterations. In addition, intracerebroventricular administration of N-nitro-L-arginine (10 microliters of a 10 mM solution) diminished the acoustic startle response. Specificity of these effects through nitric oxide was supported by the ability of the nitric oxide precursor, L-arginine, to prevent the inhibitors actions. These findings indicate that nitric oxide inhibitors interfere with the general psychophysiological status of the organism.

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Telencephalic ablation results in decreased startle response in goldfish.

Our investigation concerns the connection between the telencephalon and the startle response, mediated by reticulospinal neurons. Before surgery fish respond to the startle stimulus in 95% of the trials and 66% of the time with complete full turns. Following telencephalon removal fish respond in only 50% of the trials but make complete full turns only 7% of the time. There is no significant change found in control fish. This suggests a modulatory role of the telencephalon in regards to startle behavior.

Animals↗

Effects of single and repeated shock on perceived pain and startle response in healthy volunteers.

Contingent shock (CS) has been used in a number of studies to suppress health-threatening self-injurious behavior of individuals with mental retardation and autism. As sustained suppression is an issue of concern, research into procedural variables of CS is needed. In this study, clinical evidence was used to infer a variable that might be of relevance for the application of clinical contingent shock, that is, to assess the effect of single versus repeated shock at a specific location on the body. With pain intensity and startle response as dependent variables, shocks were administered to 48 healthy volunteers. Electric shocks were identical to those that used in clinical practice. The second shock in succession to the same location of the body produced higher pain intensity ratings than the first shock and that the third shock in succession to the same location of the body produced higher pain intensity ratings than the second shock in succession. Startle responses, however, failed to be affected in this direction. The latter result is consistent with a previous study. Our data suggest that repeated shock to the same location is likely to be more effective to establish suppression than repeated shock to different locations.

Adult↗

Effects of phencyclidine on prepulse inhibition of acoustic startle response in the macaque.

RATIONALE: Prepulse inhibition (PPI) of the acoustic startle response (ASR) provides an index of neurophysiological dysfunction in schizophrenia and a method for analyzing underlying neurochemical mechanisms. In rodents, phencyclidine (PCP) and other N-methyl-D-aspartate receptor (NMDAR) antagonists induce schizophrenia-like PPI deficits. Similar effects have recently been observed in a New World monkey species, Cebus apella. OBJECTIVES: The present study evaluates the degree to which similar effects are observed in an Old World monkey, M. fascicularis. METHODS: An initial study evaluated effects of interstimulus interval on PPI amplitude and latency. A subsequent study evaluated effects of PCP (0.25 mg/kg i.m.) on PPI of the ASR. RESULTS: Prepulses reduced both the amplitude and latency of the ASR. PCP treatment prevented both effects without affecting amplitude or latency of the ASR itself. CONCLUSIONS: These results demonstrate that both amplitude reduction and latency facilitation are observed during PPI in the monkey and are disrupted by PCP.

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The auditory startle response in progressive supranuclear palsy.

The EMG characteristics of the normal auditory startle response in man are compatible with an origin in the pontine reticular formation and with conduction down the spinal cord in a slowly conducting, possibly reticulo-spinal pathway. The startle was reduced or absent in patients with progressive supranuclear palsy, consistent with loss of neurones in the lower pontine reticular formation. In contrast, the startle was present and of normal form in patients with Parkinson's disease. However, it was delayed in onset. This result was not influenced by treatment with L-dopa. The late auditory startle in Parkinson's disease might be related to withdrawal of facilitatory input to brainstem centres from the basal ganglia.

Aged↗

Somatostatin in the pontine reticular formation modulates fear potentiation of the acoustic startle response: an anatomical, electrophysiological, and behavioral study.

The amplitude of the acoustic startle response (ASP) in rats is increased in the presence of a cue that 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 in the caudal pontine reticular nucleus (PnC) by a combination of anatomical, electrophysical, 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 somatostatinergic input to the PnC. In the second experiment, we iontophoretically applied the somatostatin receptor agonist sandostatin on PnC neurons and extracellularly recorded the activity of PnC neurons. Sandostatin had no effect on 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 blocked fear potentiation of the ASR but had no effect on the baseline ASR amplitude. The present study indicates that the 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.

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Pyrethroid insecticides and the gamma-aminobutyric acidA receptor complex: motor activity and the acoustic startle response in the rat.

Two behavioral tests, motor activity and the acoustic startle response (ASR), were used to test for dose-addition of cismethrin, a Type I, or deltamethrin, a Type II pyrethroid, with compounds active at the gamma-aminobutyric acid (GABAA) receptor complex (picrotoxin, muscimol and chlordiazepoxide). Additivity was assessed using a simplified version of isobolographic analysis using chlorpromazine and haloperidol as positive controls for dose-additivity. Dosage-effect functions for all compounds were determined for both motor activity and the ASR. The effects of various combinations of chlorpromazine (0.5-4.0 mg/kg) and haloperidol (0.05-0.2 mg/kg) on motor activity indicate dose-addition. To test for dose-addition of pyrethroids and GABAergic compounds, cismethrin (3-18 mg/kg) or deltamethrin (2-6 mg/kg) were administered 90 min before testing, either alone, or before treatment with picrotoxin (0.25-2.0 mg/kg), muscimol (0.6-2.5 mg/kg) or chlordiazepoxide (2.5-10 mg/kg) administered 20 to 30 min before testing. All compounds produced dosage-dependent decreases in motor activity. Muscimol and picrotoxin decreased ASR amplitude, increased ASR latency and reduced ASR sensitization to increasing background noise levels. Chlordiazepoxide had no effect on any measure of the ASR. Results from the interaction studies indicate dose-addition of the effects of picrotoxin and deltamethrin on motor activity and the ASR. Additivity of dose was not seen with any other combination. These data suggest that the in vivo effects of the Type II pyrethroid deltamethrin may be due in part to interaction with the picrotoxinin binding site of the GABAA receptor-ionophore complex. In addition, these results are consistent with reported differential effects of the two classes of pyrethroids on the GABAA receptor complex.

Animals↗

The vibrational startle response of the desert locust Schistocerca gregaria.

Substratum vibrations elicit a fast startle response in unrestrained quiescent desert locusts (Schistocerca gregaria). The response is graded with stimulus intensity and consists of a small, rapid but conspicuous movement of the legs and body, but it does not result in any positional change of the animal. With stimuli just above threshold, it begins with a fast twitch of the hindlegs generated by movements of the coxa-trochanter and femur-tibia joints. With increasing stimulus intensity, a rapid movement of all legs may follow, resulting in an up-down movement of the whole body. The magnitude of both the hindleg movement and electromyographic recordings from hindleg extensor and flexor tibiae muscles increases with stimulus amplitude and reaches a plateau at vibration accelerations above 20 m s(-)(2) (peak-to-peak). Hindleg extensor and flexor tibiae muscles in unrestrained animals are co-activated with a mean latency of 30 ms. Behavioural thresholds are as low as 0. 47 m s(-)(2) (peak-to-peak) at frequencies below 100 Hz but rise steeply above 200 Hz. The response habituates rapidly, and inter-stimulus intervals of 2 min or more are necessary to evoke maximal reactions. Intracellular recordings in fixed (upside-down) locusts also revealed co-activation of both flexor and extensor motor neurones with latencies of approximately 25 ms. This shows that the neuronal network underlying the startle movement is functional in a restrained preparation and can therefore be studied in great detail at the level of identified neurones.

Animals↗

Lesions of the inferior olive do not affect long- or short-term habituation of the acoustic startle response in rats.

Short- and long-term habituation of the acoustic startle response were assessed in a group of inferior olive-lesioned rats. Neither short- and long-term habituation, nor the performance of the reflex, were affected by the lesion. Since the cerebellar vermis is essential for long-term habituation of this reflex, we suggest that climbing fibres are not involved in this form of learning, which would therefore be mediated by the other cerebellar input, presumably the mossy fibres.

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Structural brain correlates of prepulse inhibition of the acoustic startle response in healthy humans.

Neural regions modulating prepulse inhibition (PPI) of the startle response, an operational measure of sensorimotor gating, are well established from animal studies using surgical and pharmacological procedures. The limbic and cortico-pallido-striato-thalamic circuitry is thought to be responsible for modulation of PPI in the rat. The involvement of this circuitry in human PPI is suggested by observations of deficient PPI in a number of neuropsychiatric disorders characterized by abnormalities at some level in this circuitry and recent functional neuroimaging studies in humans. The current study sought to investigate structural neural correlates of PPI in a sample of twenty-four right-handed, healthy subjects (10 men, 14 women). Subjects underwent magnetic resonance imaging (MRI) at 1.5 T and were assessed (off-line) on acoustic PPI using electromyographic recordings of the orbicularis oculi muscle beneath the right eye. Optimized volumetric voxel-based morphometry (VBM) implemented in SPM99 was used to investigate the relationship of PPI (prepulse onset-to-pulse onset interval 120 ms) to regional grey matter volumes, covarying for sex. Significant positive correlations were obtained between PPI and grey matter volume in the hippocampus extending to parahippocampal gyrus, basal ganglia including parts of putamen, globus pallidus, and nucleus accumbens, superior temporal gyrus, thalamus, and inferior frontal gyrus. These findings identify the relationship between PPI and grey matter availability on a highly spatially localized scale in brain regions shown to be activated in recent functional neuroimaging studies in association with PPI in healthy humans and demonstrate the validity of structural neuroimaging methods in delineating the neural mechanisms underlying human PPI.

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Startle responses in Parkinson patients during human gait.

Falls frequently occur in patients with Parkinson's disease (Bloem et al. 2001). One potential source for such falls during walking might be caused by the reaction to loud noises. In normal subjects startle reactions are well integrated in the locomotor activity (Nieuwenhuijzen et al. 2000), but whether this is also achieved in Parkinson patients is unknown. Therefore, in the present study, the startle response during walking was studied in eight patients with Parkinson's disease and in eight healthy subjects. To examine how startle reactions are incorporated in an ongoing gait pattern of these patients, unexpected auditory stimuli were presented in six phases of the step cycle during walking on a treadmill. For both legs electromyographic activity was recorded from biceps femoris and tibialis anterior. In addition, we measured the stance and swing phases of both legs, along with the knee angles of both legs and the left ankle angle. In all subjects and all muscles, responses were detected. The pattern of the responses, latency, duration, and phase-dependent modulation was similar in both groups. However, the mean response amplitude was larger in patients due to a smaller habituation rate. No correlation was found between the degree of habituation and disease severity. Moreover, a decreased habituation was already observed in mildly affected patients, indicating that habituation of the startle response is a sensitive measure of Parkinson's disease. The results complement the earlier findings of reduced habituation of blink responses in Parkinson's disease. With respect to behavioral changes in healthy subjects we observed that startle stimuli induced a shortening of the step cycle and a decrease in range of motion. In the patient group, less shortening of the subsequent step cycle and no decrease in range of motion of the knee and ankle was seen. It is argued that the observed changes might contribute to the high incidence of falls in patients with Parkinson's disease.

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Intracerebroventricularly transplanted embryonic neuronal tissue from inflammatory-resistant F344/N rats decreases acoustic startle responses in inflammatory-susceptible LEW/N rats.

Recently, we have shown that intracerebral transplantation of fetal F344/N hypothalamic tissue into LEW/N rats converts the LEW/N inflammatory-susceptible phenotype into an inflammatory-resistant phenotype in LEW/N hosts. Because LEW/N rats also exhibit relatively high acoustic startle responses (ASRs) compared to F344/N rats, in the present study we examined the effects on ASR of transplantation of F344/N hypothalamic tissue into the third ventricle of LEW/N rats. Dissected neuronal tissue from F344/N rats (Day E15-16) was implanted into the third ventricle of LEW/N rats. After 4 wk of postoperative survival, the animals' responses to acoustic startle stimuli were tested. Compared to naive and sham-operated animals, LEW/N rats transplanted with hypothalamic tissue exhibited significant decreases in ASR amplitudes. A similar decrease in ASR amplitude was observed in the group of LEW/N rats transplanted with embryonic striatal tissue. Our results indicate that the third ventricular neuronal grafts may modulate behavioral responses in the LEW/N rats. Although the mechanism of this effect is unknown, these studies suggest that intracerebral neuronal transplantation is a viable method with which to explore mechanisms of behavioral, neuroendocrine, and inflammatory response associations.

Acoustic Stimulation↗

The acoustic startle response is normal in patients with multiple system atrophy.

We investigated the acoustic startle response in eight patients with MSA and compared the results with those from a group of age matched healthy subjects. Onset latency and amplitude of the responses obtained in the orbicularis oculi, masseter and sternocleidomastoid muscles were not different in patients and control subjects. We conclude that, in spite of the pathological derangement described in brainstem reticular nuclei in MSA, the neuronal circuits mediating the auditory startle reflex are functionally preserved.

Acoustic Stimulation↗

Acoustic startle response in the opossum Monodelphis domestica in comparison with the Wistar albino rat.

The acoustic startle response (ASR) was studied in 20 gray short-tailed opossums (Monodelphis domestica) and its characteristics were compared with those obtained from responses of 20 Wistar albino rats. The animals were exposed to 10 ms, 110 dB white noise acoustic pulses in the Coulbourn apparatus. Amplitude of ASR was normalized to the weight of animals and then analyzed. The results show that probability of a freezing response is much higher in the opossums that generally respond with lower startle amplitudes in comparison to rats. These differences may reflect different emotional characteristics of the two species, different reactions to fear in opossum and/or different ecological specializations of the two species.

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Experience increases the prepulse inhibition of the acoustic startle response in mice.

The authors have previously shown that inhibition of the acoustic startle response by a prepulse increases when it is repetitively elicited over days. The present experiments show in C3H and C57 mice that this change is caused by an increase in prepulse inhibition (PPI) and not by a decrease in prepulse facilitation. This PPI increase is only evoked if prepulses and startle stimuli are repeatedly given in a temporally paired ("contingent") order, proposing an associative learning process. (Only in C57 mice, PPI was additionally increased by adaptation in the same, but not in a different, context). As an underlying mechanism for this PPI increase by experience, the authors hypothesize Hebbian plasticity of an inhibitory synapse.

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Sensory gating of the P13 midlatency auditory evoked potential and the startle response in the rat.

The human P1/P50 midlatency auditory evoked potential and the startle response (SR) have been used as measures of sensory and sensorimotor gating, respectively. In the present study, both prepulse and paired stimulus paradigms were used in order to investigate the relationship between sensory gating mechanisms of the P13 potential, the putative rodent equivalent of the P1 potential, and those of the SR. In addition, these were compared to the properties of the N40 potential, another measure of sensory gating. Simultaneous recordings from the vertex (P13 potential and N40 potential) and neck musculature (SR) showed that (1) in a prepulse paradigm, increasing the intensity of the prepulse or decreasing the interstimulus interval resulted in increased inhibition of the P13 potential, N40 potential (to a lesser degree) and the SR (to a greater degree), (2) when using a low signal-to-noise ratio between the prepulse intensity and the background level, prepulse inhibition of the SR was reduced or absent while that of the P13 potential was present, (3) the amplitude of the 'prepulse evoked' P13 potential was significantly correlated with prepulse inhibition of the P13 potential, the N40 potential and the SR, (4) in a paired identical stimulus paradigm, decreasing the interstimulus interval resulted in increased habituation of the P13 potential, N40 potential (to a lesser degree) and the SR, and (5) increasing the intensity of the paired stimulation resulted in increased habituation of the P13 potential and the N40 potential (to a lesser degree), but not of the SR. These results demonstrate the presence of prepulse inhibition of the P13 potential, the N40 potential and the SR in a parallel manner, but show certain specific differences in their responses to parametric changes.

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Stimulus specificity in the habituation of the startle response in the rat.

A series of experiments evaluated whether the habituation of the startle response of the rat to tactile and auditory cues is stimulus specific. Experiment 1 showed stimulus specificity of a short-term habituation effect, whereby the startle to the second of a pair of stimuli was significantly less when the initial stimulus involved the same rather than the different modality. Experiments 2 and 3 focused on the more persistent decrement in startle that is a result of repeated stimulation, and demonstrated that such long-term habituation to the tactile and auditory stimuli contained a stimulus specific component in addition to a generalized component. The generalized habituation observed between the tactile and auditory stimuli in the three experiments may be due to an auditory accompaniment of the tactile stimulus employed. Discussion emphasized the utility of investigating habituation in a preparation with robust specificity.

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Affective modulation of the startle response in depression: influence of the severity of depression, anhedonia, and anxiety.

BACKGROUND: The amplitude of the startle reflex response is known to be influenced by the concomitant presentation of affect-toned material--if it is positive affect-toned, the reflex is inhibited, and if it is negative affect-toned, the reflex is augmented. Abundant evidence demonstrates the utility of the affect-startle paradigm as a significant tool for measuring both positive and negative emotions. We applied this paradigm to study emotional reactivity in depression, particularly in relation to symptoms of depression, anhedonia, and anxiety. METHODS: Depressed patients (22) and controls (22) were shown a series of film clips, consisting of two clips with positive valence, two with negative valence, and two with relatively neutral valence. The startle response was measured in reaction to the acoustic startle-eliciting stimuli presented three times binaurally during each clip. RESULTS: Highly depressed and anhedonic patients, relative to controls, showed a reduced mood (self-ratings) and a lack of startle modulation in response to affective film clips whereas patients relatively low on depression/anhedonia displayed a reduced mood only with pleasant clips and a normal pattern of affective startle modulation. Anhedonia and depression were highly positively correlated but neither correlated with anxiety. Anxious patients displayed larger reflexes across all clips and showed a reduced mood modulation with pleasant, but not unpleasant, clips. LIMITATIONS: The large majority of patients was medicated with antidepressants which may have influenced the results. CONCLUSIONS. Reactivity to pleasant stimuli is diminished in patients suffering from low levels of depression and/or anhedonia, but reactivity even to unpleasant stimuli seems compromised at high levels of depression and/or anhedonia. Anxiety is associated with hyperstartle responding.

Adult↗