Acoustic Startle Response Amplitude Research Articles

The Influence of Stuttering Severity on Acoustic Startle Responses

This study examined the potential impact of stuttering severity, as measured by the Perceptions of Stuttering Inventory (Woolf, 1967) on acoustic startle responses. Three groups, consisting of 10 nonstuttering adults, 9 mild stutterering adults, and 11 moderate/severe stutterering adults, were presented with identical 95-dB acoustic stimuli to elicit acoustic startle responses across 10 trials. Electromyographic recordings of orbicularis occuli activity were used to measure individual acoustic startle responses. Participant groups failed to exhibit statistically significant differences in initial acoustic startle response amplitude, mean acoustic startle response amplitude, habituation rates, and onset latency. Acoustic startle responses were characterized by high levels of variability across all participant groups but with highest levels of variability in the moderate/severe stuttering group. The current results suggest that stuttering severity, as measured in this study, does not effectively predict acoustic startle responses in groups of adults who stutter.

Role of NMDA receptors in the syndrome of behavioral changes produced by predator stress

Effects on behavioral response to predator stress of competitive block of NMDA receptors with doses of .1, 1.0 and 10 mg/kg of CPP (3-(2-carboxypiperazin4-yl)propyl-l-phosphonic acid) were studied. An affect test battery assessed behavioral response to stress and employed hole board, elevated plus maze, light/dark box, social interaction, social avoidance and response to acoustic startle tests. Doses of 1–10 mg/kg of CPP administered ip 30 min prior to predator stress blocked the effects of predator stress on some but not all behaviors measured 8–9 days later. Predator stress normally reduces open arm exploration and risk assessment in the plus maze, decreases entries into the lighted arm of the light dark box and delays habituation of the acoustic startle response. CPP blocked all of these effects of predator stress. A dose of 10 mg/kg of CPP was required for all behaviors except habituation to startle. Block of effects on habituation to startle occurred at 1 and 10 mg/kg. Behaviors in which effects of predator stress were not blocked by CPP included reduction in unprotected head dips in the elevated plus maze and reduced social interaction. In addition, predator stress was without effect on social avoidance measured with the Haller test. These findings extend previous work showing NMDA receptor dependence of effects of predator stress on behavior in the elevated plus maze and on amplitude of acoustic startle response. Novel findings include NMDA receptor dependence of predator stress effects on light dark box behavior and startle habituation. Taken together, the findings add to a body of evidence showing that a syndrome of behavioral changes follows predator stress. Components of this syndrome of behavioral changes likely depend on changes in separable neural substrates initiated in part by NMDA receptors as well as by other neurochemical means.

Acoustic startle response in the opossum <i>Monodelphis domestica</i> 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.

Effects of sex and estrous cycle on modulation of the acoustic startle response in mice

Potential sex differences in amplitude, habituation, prepulse inhibition (PPI) and prepulse facilitation (PPF) of the acoustic startle response (ASR) were investigated using male and female mice from the two different inbred mouse strains C57BL/6J (C57) and C3H. Furthermore, the effects of the estrous cycle were tested. The estrous cycle appeared to have no effect on ASR amplitude, habituation, PPF and PPI, the latter being in contrast to results in rats and humans. While sex had no effect on PPI or PPF, males exhibited higher startle amplitudes than females, irrespective of strain, which we discuss to be due to increased male anxiety. In addition, long-term habituation was stronger in C57 males and short-term habituation was weaker in C3H males with respect to females. These results provide evidence for influence of the reproductive hormones on startle reactivity and startle habituation; we therefore conclude that future studies involving genetic influences on behavior using inbred strains are only complete if both sexes are included.

Prepulse inhibition and habituation of acoustic startle response in male MDMA ('ecstasy') users, cannabis users, and healthy controls.

Chronic administration of 3,4-methylenedioxymethamphetamine (MDMA) is associated with long-term depletion of serotonin (5-HT) and loss of 5-HT axons in the brains of rodents and nonhuman primates. Despite the broad database concerning the selective serotonergic neurotoxicity of recreational MDMA consumption by humans, controversy still exists with respect to the question of whether the well-known functional consequences of these neurotoxic effects, such as memory impairment, were caused by chronic 5-HT deficiency. Habituation and prepulse inhibition (PPI) of the acoustic startle response (ASR) can be used as a marker of central serotonergic functioning in rodents and humans. Thus, we investigated the functional status of the central serotonergic system in chronic but abstinent MDMA users by measuring PPI and habituation of ASR. PPI and habituation of ASR were measured in three groups. The first group (MDMA group) included 20 male drug-free chronic users of MDMA; the second group (cannabis group) consisted of 20 male drug-free chronic users of cannabis; and the third group (healthy controls) comprised 20 male participants with no history of illicit drug use. Analysis revealed significantly increased PPI of MDMA users compared to those of cannabis users and healthy controls. Cannabis users and healthy controls showed comparable patterns of PPI. There were no differences in habituation among the three groups. These results suggest that the functional consequences of chronic MDMA use may be explained by 5-HT receptor changes rather than by a chronic 5-HT deficiency condition. Use of cannabis does not lead to alterations of amplitude, habituation, or PPI of ASR.

Electrolytic, but not neurotoxic, lesions to the lateral tegmental tract increase acoustic startle amplitude and reduce startle stimulus-induced freezing

Startle amplitude and startle stimulus-induced freezing (an index of fear) were measured in a standard acoustic startle response (ASR) paradigm in male Sprague–Dawley rats. Groups with electrolytic lesions to the lateral tegmental tract (LTG) or with axon-sparing lesions to the area around LTG made with the neurotoxin NMDA were compared with vehicle-injected or sham operated control groups on these response measures. Replicating previous results ( Leaton & Brucato, 2001), electrolytic lesions to LTG significantly reduced freezing and produced a persistent 300% increase in ASR amplitude compared with all other groups. The NMDA lesions had no effect on freezing or on ASR amplitude compared with the controls. In additional testing the rats with electrolytic lesions to LTG did not differ from controls in the acquisition or retention of context freezing using a footshock unconditioned stimulus. The data made a small, but necessary, step in further clarifying two pathways that modify ASR. The source of the descending pathway that provides tonic inhibition of the sensory input to the ASR circuitry is not within the LTG. The ascending pathway that carries the fear-inducing dimensions of the acoustic stimulus to the amygdala by way of the medial geniculate nucleus does not have an intermediate synapse in the area within LTG.

The acoustic startle response as an effective model for elucidating the effect of genes on the neural mechanism of behavior in mice

One current approach in investigating the neural basis of behavior is to use mutant mice with specific genetic alterations which affect neural functions. We are convinced that this approach is only effective if a behavioral model with sufficiently known underlying neuronal mechanisms is used. We present a model system which is well-suited for the above approach. Because the neural basis is known in great detail, in the startle system behavioral results can be very well interpreted. This is demonstrated here by using footshock sensitization of the acoustic startle response (ASR) as an example. Sensitization is elicited by aversive stimuli such as electric footshocks and causes an increase in ASR amplitude. The present experiment showed that this ASR increase is not due to a drop in the startle threshold but to increased gain in the response to suprathreshold stimuli. This makes it possible to draw conclusions about the neuronal site of the startle threshold in the startle pathway and the synapse at which the gain shift during sensitization occurs. The possibility of interpreting behavioral output on a well known neural basis (as demonstrated here) makes the ASR a promising model system for investigating (neuro-) genetic influences of behavior.

Startle amplitude and fear in an acoustic startle paradigm: Lesions to the brachium of the inferior colliculus or the lateral tegmental tract.

In 2 experiments, startle amplitude and startle stimulus-induced freezing (an index of fear) were measured in an acoustic startle response (ASR) paradigm in rats. Lesions to lateral tegmental tract (LTG), a pathway medial to brachium of the inferior colliculus (BIC), significantly decreased freezing and produced a persistent 5-fold increase in ASR amplitude compared with sham-operated controls. Lesions to BIC increased both ASR amplitude (2-fold) and freezing. Neither BIC nor LTG lesions affected startle amplitude when startle was elicited by a brief footshock stimulus. Characteristics of the lesion effects were tested with manipulations of interstimulus interval, stimulus intensity, and prepulse inhibition. The data suggest (a) an ascending pathway medial to BIC that carries the fear-inducing dimensions of an acoustic stimulus and (b) a descending pathway that provides tonic inhibition of the sensory input to the ASR circuitry.

Startle amplitude and fear in an acoustic startle paradigm: Lesions to the brachium of the inferior colliculus or the lateral tegmental tract.

In 2 experiments, startle amplitude and startle stimulus-induced freezing (an index of fear) were measured in an acoustic startle response (ASR) paradigm in rats. Lesions to lateral tegmental tract (LTG), a pathway medial to brachium of the inferior colliculus (BIC), significantly decreased freezing and produced a persistent 5-fold increase in ASR amplitude compared with sham-operated controls. Lesions to BIC increased both ASR amplitude (2-fold) and freezing. Neither BIC nor LTG lesions affected startle amplitude when startle was elicited by a brief footshock stimulus. Characteristics of the lesion effects were tested with manipulations of interstimulus interval, stimulus intensity, and prepulse inhibition. The data suggest (a) an ascending pathway medial to BIC that carries the fear-inducing dimensions of an acoustic stimulus and (b) a descending pathway that provides tonic inhibition of the sensory input to the ASR circuitry.

The auditory pathways: Startle amplitude and fear in an acoustic startle response paradigm in rats

Startle amplitude and startle-stimulus-induced freezing were measured in a standard acoustic startle response (ASR) paradigm in rats. Subsequently conditioned freezing was measured to an auditory conditioned stimulus (CS) with a foot-shock unconditioned stimulus (US). In Experiment 1, lesions to the brachium of the inferior colliculus (BIC) increased ASR amplitude and freezing. Lesions to the nucleus of the trapezoid body abolished ASR and marginally reduced freezing. Neither lesioned group differed from controls in conditioned freezing to the auditory CS. In Experiment 2, lesions to the medial geniculate nucleus (MGN) increased ASR amplitude, as did BIC lesions, but reduced freezing, while BIC lesions increased freezing. MGN lesions, unlike BIC lesions, significantly attenuated freezing to the auditory CS, as compared with controls. Both groups startled less than controls to a weak shock stimulus. The data suggest an ascending auditory pathway medial to BIC that carries the fear-inducing dimension of an acoustic stimulus and a descending pathway in BIC that provides tonic inhibition of the acoustic input to the ASR circuitry.

Acoustic startle and open-field behavior in mice bred for magnitude of swim analgesia

Acoustic startle response (ASR) and open-field activity was examined in the 46th generation of mice that have been selectively bred for high analgesia (HA) and for low analgesia (LA) induced by 3-min swimming in 20°C water. These lines were earlier found to differ in brain opioid receptor density and in the expression of opioid-mediated phenomena, as analgesic sensitivity to opiates and reversibility of swim stress-induced analgesia (SSIA) by naloxone. For comparison, a randomly bred control (C) line was used. To measure the amplitude of ASR, the mice were exposed to 110-dB acoustic stimuli in a Coulbourn apparatus. In saline-injected mice, the ASR force was found significantly lower in the LA than in the HA, as well in the C line, but did not differ between the two last lines. Naltrexone hydrochloride (10 mg/kg IP 30 min before ASR testing) augmented the startle in the opioid receptor-dense HA line, but had no effect in the opioid receptor-deficient LA line, as well in the C line; therefore, the ASR magnitude in naltrexone-injected HA mice was significantly higher compared to the C line. HA mice displayed less activity in an open-field test; that is, they remained immobile longer in the center of the field, and thereafter performed less ambulation and less rearing against the wall compared to the LA line. Naltrexone failed to modify the open-field activity in any line. The results confirm that the pattern of ASR depends on the genetic makeup of the animals. The higher amplitude of ASR, taken together with the lower open-field activity of HA mice, can be interpreted in terms of higher anxiety level, compared to the LA line. It is suggested that the higher ASR in HA mice relies on a nonopioid mechanism, which is tonically inhibited by the opioid system.

Neural transplants: effects on startle responses in neonatally MSG-treated rats

Neonatal monosodium glutamate (MSG) treatment has been associated with disfunctions in stress responses. Therefore, the present study aimed at examining the acoustic startle response (ASR) in MSG-treated rats and the effects of fetal neural transplantation. Male and female rats were given MSG (4 mg/g) or saline on alternate days from days 2–10 after birth. To determine whether fetal transplants could reverse behavioral impairments observed in MSG-treated rats, at 12 days of age MSG-treated rats received either arcuate nucleus (AN), cortical fetal grafts, or sham surgery into the third ventricle. ASR amplitude was measured at 35–40 days of age, and again in adulthood. MSG produced the expected decrease in the density of hypothalamic neuropeptide Y (NPY) and tyrosine hydroxylase (TH) in the AN area. Corticotropin-releasing factor (CRF) neurons/fibers were not affected by MSG. Pituitary atrophy was observed in all MSG rats. We report a permanent increase in the amplitude and reduction in short-term habituation of ASR in all MSG-treated rats. No effect was observed on long-term habituation in male rats. Cortical, but not AN tissue significantly reduced the magnitude of ASR in MSG animals. The results are discussed in terms of the central pathways mediating ASR, in particular hypothalamo-amygdala connections. It is considered that nonspecific factors mediate recovery produced by cortical tissue grafts, as observed in other models of neural transplan-tation.

Neurotoxicity of manganese chloride in neonatal and adult CD rats following subchronic (21-day) high-dose oral exposure.

The purpose of this study was to evaluate the relative sensitivity of neonatal and adult CD rats to manganese-induced neurotoxicity. Identical oral manganese chloride (MnCl(2)) doses (0, 25, or 50 mg kg(-1) body wt. day(-1)) were given to neonatal rats throughout lactation (i.e. from postnatal day (PND) 1 through 21) and to adult male rats for 21 consecutive days. The MnCl(2) doses administered to neonates were ca. 100-fold higher than those resulting from the consumption of an equivalent volume of rat's milk. Rats were assessed using similar behavioral and neurochemical evaluations. Several statistically significant changes occurred in Mn-exposed rats relative to control animals. Neonates given the high dose of MnCl(2) had reduced body weight gain. An increased pulse-elicited acoustic startle response amplitude was observed in neonates from both MnCl(2) treatment groups on PND 21. Increased striatal, hippocampal, hindbrain and cortical Mn concentrations were observed in all Mn-exposed neonates on PND 21. Increased hypothalamic and cerebellar Mn concentrations were also observed on PND 21 in neonates from the high-dose group only. Increased striatal, cerebellar and brain residue Mn concentrations were observed in adult rats from the high-dose group. Increased striatal dopamine and 3,4-dihydroxyphenylacetic acid levels were observed only in PND 21 neonates from the high-dose group. No treatment-related changes were observed in clinical signs, motor activity (assessed in neonates on PND 13, 17, 21 +/- 1 and in adults), passive avoidance (assessed in neonates on PND 20 +/- 1 and in adults) or neuropathology (assessed in PND 21 neonates only). The results of our experiment suggest that neonates may be at greater risk for Mn-induced neurotoxicity when compared to adults receiving similar high oral levels of Mn.

Effects of exposure to an augmented acoustic environment on auditory function in mice: roles of hearing loss and age during treatment

The effects of exposure to an augmented acoustic environment (AAE) on auditory function were evaluated in mouse strains that exhibit various degrees and time courses of progressive hearing loss (BXD-22, BXD-12, BXD-16, BXD-14, BALB/cJ), and in normal-hearing CBA/CaJ mice. Beginning at age 25 days, mice were exposed 12 h every night to a 70 dB SPL broadband noise AAE. The AAE was maintained for at least 30 days in each strain. Same-strain control mice were age-matched and maintained under normal vivarium acoustic conditions. The auditory brainstem response (ABR), acoustic startle response amplitude, and prepulse inhibition (PPI) were used to assess the auditory system. Exposure to the AAE resulted in improved auditory performance (better PPI, lower ABR thresholds) when hearing impairment was present, but not when hearing was normal. The ameliorative effects occurred irrespective of a mouse’s age at the onset of hearing loss, as long as initiation of AAE treatment preceded the occurrence of severe hearing loss. If AAE treatment was delayed beyond such a point, loss of threshold sensitivity progressed as usual, although PPI could still benefit. Finally, AAE treatment can slow, but not prevent, the occurrence of severe genetically determined hearing loss.

The superior olivary complex is necessary for the full expression of the acoustic but not tactile startle response in rats

The acoustic startle response (ASR) in rats is mediated by an oligosynaptic pathway from the cochlea via the brainstem to spinal and cranial motoneurons. The present study tested whether the superior olivary complex (SOC) plays a role in the mediation of the ASR. The SOC receives auditory information from the ventral cochlear nuclei and projects to the caudal pontine reticular nucleus (PnC), the sensorimotor interface of the ASR. Axon-sparing excitotoxic lesions of the SOC strongly reduced the ASR amplitude and slightly prolonged ASR onset and peak latencies. The integrity of PnC which is adjacent to the SOC was confirmed by testing the tactile startle response which was not affected by SOC lesions. We suggest that the SOC is necessary for a full expression of the ASR and discuss possible auditory input structures involved in the mediation of the ASR.

Fear-Potentiated Startle Response in Mice: Genetic Analysis of the C57BL/6J and DBA/2J Intercross

The role of genetic factors in the fear-potentiated startle (FPS) response was examined in the inbred C57BL/6J (B6) and DBA/2J (D2) mouse strains. Mice in the D2 strain displayed a significant potentiation in the acoustic startle response (ASR) when presented with a visual condition stimulus (CS) previously paired with an aversive unconditioned stimulus (US). The maximal FPS response was observed following 20 conditioning trials but a near maximal response was noted following as few as five trials. Forty conditioning trials produced a significant reduction in the FPS response that may be related to overtraining. The FPS response in the B6 strain was significantly lower than the D2 strain, regardless of the number of conditioning trials. The contrasting FPS responses were not related to differences in auditory sensitivity known to exist between these strains. Analysis of a full Mendelian cross formed from the B6 and D2 strains found that the FPS response was a highly heritable trait, best described by a simple additive model of inheritance and with a broad-sense heritability of 0.46. The distribution of the FPS response in F2 hybrids formed from the intercross of the D2 and B6 strains was continuous which suggests a multigenic substrate. The light + noise and noise-alone trial types were highly correlated, but no association was detected between the baseline ASR amplitude and the FPS response. Mice from the phenotypic extremes of the F2 distribution displayed FPS responses that were more extreme than either of the progenitor strains. However, both baseline startle amplitude and the salience of auditory stimuli did not differ in these groups. The results of this study confirm an early report by Falls et al. (1997), and provide additional quantitative genetics information necessary for the eventual mapping of the chromosomal regions or genes associated with the FPS response in mice.

Genetic Association Between Chronic Ethanol Withdrawal Severity and Acoustic Startle Parameters in WSP and WSR Mice

The present study examined the genetic association between chronic ethanol withdrawal severity and acoustic startle response (ASR) in replicated lines of mice selected for high (Withdrawal Seizure-Prone; WSP) and low (Withdrawal Seizure-Resistant; WSR) susceptibility to handling-induced convulsions after withdrawal from chronic exposure to ethanol. Any differences on a nonselected (correlated) trait between the opposite-selected lines is strong evidence for pleiotropic effects of the genes fixed by selection. Naive WSP and WSR mice of both replicates were placed in startle chambers and exposed to a series of white noise stimuli of different intensities. In Experiment 1, two parameters [the maximal acoustic startle response (Rmax), and the sound intensity necessary to produce 50% of the maximal startle response (dB50)] were obtained from a least-squares nonlinear regression by fitting data for each subject to a sigmoidal function that best described the relationship between sound intensity and mean ASR. Response habituation of WSP and WSR mice to a repeated acoustic stimulus of high intensity was examined in Experiment 2. When ASR amplitude was plotted versus sound intensity, the sigmoid intensity-response curves of both WSP replicates were shifted to the right relative to the responses of WSR mice, which suggested decreased startle sensitivity in the WSP animals. Statistical analysis showed that naive WSP mice were less sensitive (higher dB50) to acoustic stimulation than Seizure-Resistant animals whereas Rmax was similar for both lines. The selected lines also differed in their responses to repeated acoustic stimulation, with WSP mice demonstrating greater habituation. Results of the present study suggest some common genetic mechanisms underlying behavioral responsiveness to acoustic stimulation and severity of ethanol withdrawal.

Changes of the acoustic startle reflex in rats with radiation-induced hippocampal lesion

The main question of the study was: to what extent does a neonatal radiation-induced hippocampal lesion lead to emotional changes in adulthood? Acoustic startle response (ASR) was studied in two groups of adult rats. The rats from the first group (14 animals) were exposed to neonatal x-ray irradiation. Their ASR were compared with those from the 10 intact rats that formed a control group. The ASR was tested during two sessions with different illumination of the acoustic chamber. During the first session the rats were tested in the darkness while during the second test the acoustic chamber was illuminated with a 15 W bulb. Irradiation resulted in a significant reduction of granule cells of the hippocampus (about 55%). The lesion resulted in emotional and behavioral changes evidenced by modification of the ASR. The irradiated rats exhibited a significantly increased amplitude of the startle response. In contrast to the light condition, the darkness context caused a decline of the ASR amplitude in the control group and failed to elicit significant changes in the lesioned animals. The results support the hypothesis that hippocampal lesions disrupt motor inhibition.

Prolonged exposure to an augmented acoustic environment ameliorates age-related auditory changes in C57BL/6J and DBA/2J mice

The effects of exposure to an augmented acoustic environment (AAE) on auditory function were evaluated in mouse strains that exhibit high-frequency hearing loss beginning during young adulthood (the C57BL/6J strain [C57]) or around the time of weaning/adolescence (the DBA/2J strain [DBA]). Beginning at age 25 days, mice were exposed 12 h every night to a 70 dB SPL broad-band noise AAE. The AAE was maintained until age 14 months in C57 mice and 9 months in DBA mice. Control mice were age-matched and maintained under normal vivarium acoustic conditions. The auditory brainstem response (ABR), acoustic startle response amplitude, and prepulse inhibition (PPI) were used to assess the auditory system. Exposure to the AAE resulted in improved auditory performance in both strains (better PPI, lower ABR thresholds, bigger startle amplitudes).

Effect of nonaversive and aversive stimulations in infancy on the acoustic startle response in adult rats

Two groups, each consisting of 8 three-week-old rat pups, were exposed to different behavioral treatments with the aim to determine how the experimental manipulation influenced their adult emotional reactivity. Every day for two weeks the pups from the first group received 15 min of handling whereas the animals from the second group were exposed to various aversive stimuli, differing each day. Following these manipulations, after as-day break the acoustic startle response (ASR) was measured in all animals and the testing was repeated after another four weeks. Statistical analysis of the data revealed significant differences between groups in the ASR parameters. Surprisingly, in the test which directly followed the treatment the mean ASR amplitudes were similar in both groups. Highly significant differences, however, were observed in the ASR amplitude four weeks later. The rats from the handling group responded with greater amplitudes. The latency of the ASR was significantly shorter in the nonaversive group compared with the second group exposed to aversive stimuli. The results suggest that early exposure to aversive stimulation significantly decreases rats emotional reactivity whereas nonaversive and impoverished stimulation clearly elevates arousal levels when the animal is placed in a novel situation.