Influence of long-term sensitization on long-term habituation of the acoustic startle response in rats: central gray lesions, preexposure, and extinction

The relation between long-term decrements of the acoustic startle response in rats and the development of freezing behavior during habituation training was examined. Freezing behavior developed over the initial trials of habituation training, and the rate of long-term response decrements was found to be inversely related to the development of freezing. Manipulations (neurological or behavioral) that either reduced the level of freezing or retarded its development promoted startle response decrements. In Experiment 1, rats receiving electrolytic lesions of the ventrolateral periaqueductal gray demonstrated both accelerated long-term startle response decrements and retarded development of freezing behavior. In Experiment 2, preexposure to the startle apparatus (i.e., latent inhibition) accelerated long-term startle decrements and inhibited development of freezing. In Experiment 3, exposure to the startle apparatus following initial habituation training (i.e., extinction) reduced both freezing behavior and startle response amplitudes. The results are discussed in terms of the influence of Pavlovian fear conditioning on long-term habituation of the acoustic startle response.     

Potentiation of the acoustic startle response by a conditioned stimulus paired with acoustic startle stimulus in rats

The hypothesis that the standard acoustic startle habituation paradigm contains the elements of Pavlovian fear conditioning was tested. In a potentiated startle response paradigm, a startle stimulus and a light conditioned stimulus (CS) were paired. A startle stimulus then was tested alone or following the CS. Freezing behavior was measured to index conditioned fear. The startle response was potentiated on CS trials, and rats froze more in CS than in non-CS periods. In Experiment 1, response to a previously habituated, weak startle stimulus was potentiated. In Experiment 2, response to the same stimulus used as the unconditioned stimulus (US) in training was potentiated. This CS-potentiated response retarded the course of response decrements over training sessions as compared with an explictly unpaired control group. Conditioned fear is a standard feature of this habituation paradigm, serves to potentiate the startle response, and provides an associative dimension lacking in the habituation process per se.     

Air-puff-elicited startle: Habituation over trials and measurement of a hypothetical emotional response

In the first of two experiments, it was demonstrated that an air puff elicited a reliable startle reflex in rats which showed no habituation over 50 trials. In the second study an attempt was made to measure an emotional response by recording startle reactions to the air puff during presentation of a presumed fear-eliciting CS. It was concluded that the air-puff-elicited startle reflex can be employed as an indirect measure of a hypothetical emotional response.     

惊跳反射的生理心理机制

惊跳反射作为动物及人类在应对意外刺激或遇到险情时的一种避险保护反应,具有重要的生物学意义。以往的研究较多关注听觉惊跳反射,在反应指标上多采用眼部及面部表情肌的反应,如眨眼反射。惊跳反射的生理机制为突发性强刺激直接传向杏仁核的直接通路所致。惊跳反射增强的心理机制可能为致敏作用或恐惧性条件作用,而惊跳反射衰减的心理机制可能是适应、前脉冲抑制或愉快衰减。未来的研究应关注视觉惊跳反射,观察全身躯体姿势维持肌肉群的反应模式,并以先进设备对惊跳反射的信息加工脑机制进行深入的研究     

Contextual control of long-term habituation in rats

This study examined contextual control of long-term habituation and whether such effects are dependent on the habituating response system. Habituation of the acoustic startle response transferred from the home cage to the testing context, whereas habituation of lick suppression was context specific (Experiments 1 and 2). Contextual control of habituation was demonstrated between 2 experimental contexts for lick suppression to a tone (Experiment 3) and bar-press suppression to a light (Experiment 4). Experiment 5 extinguished habituation of lick suppression and the orienting response to a tone with 27 exposures to the habituation context. Context specificity of both responses also was found. Previous failures to demonstrate contextual control of habituation may be due to the choice of response system and to less sensitive procedures to detect response recovery. The habituation mechanism for startle is independent from the process or processes that underlie habituation in other response systems, but the nature of these mechanisms is not yet known.     

The effects of cross-fostering on inherent sensorimotor gating deficits exhibited by Brattleboro rats

Prepulse inhibition (PPI) of the startle reflex is an operational measure of sensorimotor gating, a process critical to normal cognitive function. Researchers (D. Feifel & K. Priebe, 2001) have identified PPI deficits in the Brattleboro rat, a genetically vasopressin-deficient strain that is derived from the Long Evans rat. The absence of vasopressin, a neuropeptide involved in affiliative behaviors, may adversely affect the rearing of offspring by Brattleboro dams, perhaps accounting for their attenuated PPI. Cross-fostering of Long Evans and Brattleboro pups did not alter the PPI deficits in Brattleboro rats. However, the magnitude and habituation of the startle response, which normally differs between Brattleboro and Long Evans rats, was not different in cross-fostered rats. The authors' results indicated that abnormal rearing by Brattleboro dams may contribute to the startle magnitude and habituation abnormalities in Brattleboro Rats but not to their PPI deficits, suggesting that their sensorimotor gating deficits result from their genetic deviation from Long Evans rats.     

Does anxiety sensitivity correlate with startle habituation? An examination in two independent samples

Individuals with anxiety disorders have previously demonstrated abnormal habituation to aversiveness over time. As anxiety sensitivity (AS), or an individuals' propensity to fear of anxiety-related sensations, has been shown to be a risk factor for anxiety disorders (particularly panic disorder), the present study examined whether AS was also associated with abnormal habituation. This association was examined in two independent samples of undergraduates (N_total=178). Habituation was operationalised as the reduction in startle response to multiple startle probes presented over 2.5 minutes and three definitions of this reduction were employed. Results indicated that individuals with higher levels of AS evidenced deficits in startle habituation, but the strength of this relationship was somewhat dependent on the definition of startle habituation, with the most robust definition being an analysis of participants' individual slopes across all nine blinks. The present findings suggest that startle habituation is a key mechanism underlying AS, and may help elucidate the role this risk factor plays in the pathogenesis of anxiety disorders.     

Habituation and sensitization of acoustic startle: opposite influences of dopamine D1 and D2-family receptors

The startle response evoked by repeated presentation of a loud acoustic stimulus is regulated by the independent processes of sensitization and habituation. While schizophrenia is associated with information processing impairments, there is conflicting evidence regarding the existence of habituation deficits in schizophrenic patients. Recent clinical evidence, however, indicates that patients with schizophrenia display exaggerated startle sensitization and diminished habituation. Given the linkage between dopaminergic abnormalities and schizophrenia, the goal of the present investigation was to examine the effect of deleting D₁ and D₂-like dopamine receptors on sensitization and habituation of the acoustic startle reflex in mice. For these experiments, the acoustic startle reflex was assessed in dopamine D₁, D₂, and D₃ receptor wild-type (WT) and knockout (KO) mice on a C57BL/6J background, using a methodology that can measure both sensitization and habituation. Mice lacking the D₁ receptor gene displayed enhanced sensitization, along with a decrease in the amount of habituation that occurs in response to repetitive presentations of a startling stimulus. Conversely, the loss of the dopamine D₂ or D₃ receptor gene produced a sensitization deficit and a significant increase in habituation. The behavioral phenotype exhibited by D₁ receptor KO mice is clearly distinct from that of the D₂ and D₃ receptor KO mice. The findings in D₁ receptor KO mice are reminiscent of the abnormalities observed in schizophrenic patients tested in comparable startle paradigms, and indicate that D₁ agonists may possess therapeutic efficacy against the information processing deficits associated with schizophrenia.     

Fear-potentiated startle conditioning to explicit and contextual cues in Gulf War veterans with posttraumatic stress disorder

Aversive conditioning to explicit and contextual cues was examined in Gulf War veterans with and without posttraumatic stress disorder (PTSD) by use of the startle reflex methodology. Veterans participated in a differential aversive conditioning experiment consisting of 2 sessions separated by 4 or 5 days. Each session comprised two startle habituation periods, a preconditioning phase, a conditioning phase, and a postconditioning extinction test. In contrast to the non-PTSD group, the PTSD group showed a lack of differential startle response in the presence of a conditioned stimulus with or without an unconditioned stimulus in Session 1 and an increase in the baseline startle response during Session 2. The PTSD group also exhibited normal differential conditioning following reconditioning in Session 2. These data suggest that individuals with PTSD tend to generalize fear across stimuli and are sensitized by stress.     

The effect of temporal separation and prior habituation upon preconditioning

The effect of temporal separation and prior habituation was tested by measuring response transfer in a shuttle box following different initial treatments. Thirty hooded rats were split into three main groups and six sub-groups. One main group was preconditioned with concurrent light and sound stimuli, another with temporally spaced stimuli, and a control group had no preconditioning. Half of each main group was permitted to explore the apparatus before preconditioning on the supposition that this might reduce emotionality and hence reduce startle or attention responses.

It was found that concurrent stimulation produced significantly greater response transfer than in controls, whereas preconditioning with spaced stimuli did not. Prior habituation produced no significant effect on the amount of response transfer.     

A behavioral and genetic dissection of two forms of olfactory plasticity in Caenorhabditis elegans: adaptation and habituation

Continuous presentation of an olfactory stimulus causes a decrement of the chemotaxis response in the nematode Caenorhabditis elegans. However, the differences between the learning process of habituation (a readily reversible decrease in behavioral response) and other types of olfactory plasticity such as adaptation (a decrement in response due to sensory fatigue, which cannot be dishabituated) have not been addressed. The volatile odorant diacetyl (DA) was used within a single paradigm to assess the distinct processes of olfactory adaptation and habituation. Preexposing and testing worms to 100% DA vapors caused a chemotaxis decrement that was not reversible despite the presentation of potentially dishabituating stimuli. This DA adaptation was abolished in worms with an odr-10 mutation (encoding a high-affinity DA receptor on the AWA neuron), even though naive chemotaxis remained unaffected. Conversely, DA adaptation remained intact in odr-1 mutants (defective in AWC neuron-mediated olfactory behavior), even though naive chemotaxis to DA decreased. Surprisingly, exposure to vapors of intermediate concentrations of DA (0.01% and 25%) did not cause worms to exhibit any response decrement. In contrast to preexposure to high DA concentrations, preexposure to low DA concentrations (0.001%) produced habituation of the chemotaxis response (a dishabituating stimulus could reverse the response decrement back to baseline levels). The distinct behavioral effects produced by DA preexposure highlight a concentration-dependent dissociation between two decremental olfactory processes: adaptation at high DA concentrations versus habituation at low DA concentrations.     

Auditory habituation in the fetus and neonate: an fMEG study

Habituation – the most basic form of learning – is used to evaluate central nervous system (CNS) maturation and to detect abnormalities in fetal brain development. In the current study, habituation, stimulus specificity and dishabituation of auditory evoked responses were measured in fetuses and newborns using fetal magnetoencephalography (fMEG). An auditory habituation paradigm consisting of 100 trains of five 500 Hz tones, one 750 Hz tone (dishabituator) and two more 500 Hz tones, respectively, were presented to 41 fetuses (gestational age 30–39 weeks) and 22 newborns or babies (age 6–89 days). A response decrement between the first and fifth tones (habituation), an increment between the fifth tone and the dishabituator (stimulus specificity) and an increment between the fifth (last tone before the dishabituator) and seventh tones (first tone after the dishabituator) (dishabituation) were expected. Fetuses showed weak responses to the first tone. However, a significant response decrement between the second and fifth tones (habituation) and a significant increment between the fifth tone and the dishabituator (stimulus specificity) were found. No significant difference was found for dishabituation nor was a developmental trend found at the group level. From the neonatal data, significant values for stimulus specificity were found. Sensory fatigue or adaptation was ruled out as a reason for the response decrement due to the strong reactions to the dishabituator. Taken together, the current study used fMEG to directly show fetal habituation and provides evidence of fetal learning in the last trimester of pregnancy.     

Habituation and the human evoked potential

Habituation of human scalp-recorded cerebral evoked potentials was studied in response to auditory and visual repetitive stimuli of different intensities. Changes in magnitudes of evoked potentials with stimulus repetition were examined according to the parametric characteristics of habituation, generalization, and dishabituation. In addition, tests of the predictions of two theories of habituation were made regarding the degree and direction of intensity generalization of habituation. Both auditory and visual evoked potentials exhibited decrements in response magnitudes across the repetitive stimuli consistent with the parametric criteria of habituation. Early evoked potential peak components showed a pattern of intensity generalization of habituation consistent with the predictions of the dual-process theory of habituation. Intensity generalization of late evoked potential peak components occurred in a manner more consistent with the predictions of the stimulus comparator theory of habituation. These results provide further evidence that evoked potentials can be used as electrophysiological indexes of plasticity in humans.     

Differential role of inhibition in habituation of two independent afferent pathways to a common motor output

Many studies of the neural mechanisms of learning have focused on habituation, a simple form of learning in which a response decrements with repeated stimulation. In the siphon-elicited siphon withdrawal reflex (S-SWR) of the marine mollusk Aplysia, the prevailing view is that homosynaptic depression of primary sensory afferents underlies short-term habituation. Here we examined whether this mechanism is also utilized in habituation of the tail-elicited siphon withdrawal reflex (T-SWR), which is triggered by an independent, polysynaptic afferent pathway that converges onto the same siphon motor neurons (MNs). By using semi-intact preparations in which tail and/or siphon input to siphon MNs could be measured, we found that repeated tail stimuli administered in the presence of a reversible conduction block of the nerves downstream of the tail sensory neurons (SNs) completely abolished the induction of habituation. Subsequent retraining revealed no evidence of savings, indicating that the tail SNs and their immediate interneuronal targets are not the locus of plasticity underlying T-SWR habituation. The networks closely associated with the siphon MNs are modulated by cholinergic inhibition. We next examined the effects of network disinhibition on S-SWR and T-SWR habituation using an Ach receptor antagonist d-tubocurarine. We found that the resulting network disinhibition disrupted T-SWR, but not S-SWR, habituation. Indeed, repeated tail stimulation in the presence of d-tubocurarine resulted in an initial enhancement in responding. Lastly, we tested whether habituation of T-SWR generalized to S-SWR and found that it did not. Collectively, these data indicate that (1) unlike S-SWR, habituation of T-SWR does not involve homosynaptic depression of SNs; and (2) the sensitivity of T-SWR habituation to network disinhibition is consistent with an interneuronal plasticity mechanism that is unique to the T-SWR circuit, since it does not alter S-SWR.     

Habituation in normal and Down's syndrome fetuses.

The ability of ten normal and two Down's syndrome fetuses to habituate to a repeated auditory stimulus was assessed. The normal fetuses were assessed on two separate occasions during the final trimester of pregnancy. The number of trials to habituate and latency to respond were recorded. The results demonstrated that all normal fetuses exhibited a decrement in response to repeated presentations of the stimulus, a 250-Hz sine wave. This was the result of habituation and not fatigue since fetuses recovered responding upon presentation of a new (500 Hz) stimulus and habituated faster on re-presentation of the original stimulus. The performance of fetuses remained stable over the two testing periods. The response of the Down's syndrome fetuses was different to that of normal fetuses rarely overlapping indices of habituation exhibited by normal fetuses. The study concludes that habituation may be a powerful tool to examine the behavioural and sensory development of the fetus and may be of use in the antenatal assessment of the existence and severity of neural abnormality.     

Habituation in normal and down's syndrome fetuses

The ability of ten normal and two Down's syndrome fetuses to habituate to a repeated auditory stimulus was assessed. The normal fetuses were assessed on two separate occasions during the final trimester of pregnancy. The number of trials to habituate and latency to respond were recorded. The results demonstrated that all normal fetuses exhibited a decrement in response to repeated presentations of the stimulus, a 250-Hz sine wave. This was the result of habituation and not fatigue since fetuses recovered responding upon presentation of a new (500 Hz) stimulus and habituated faster on re-presentation of the original stimulus. The performance of fetuses remained stable over the two testing periods. The response of the Down's syndrome fetuses was different to that of normal fetuses rarely overlapping indices of habituation exhibited by normal fetuses. The study concludes that habituation may be a powerful tool to examine the behavioural and sensory development of the fetus and may be of use in the antenatal assessment of the existence and severity of neural abnormality.     

Neurogenetic approaches to habituation and dishabituation in Drosophila

We review work in the major model systems for habituation in Drosophila melanogaster, encompassing several sensory modalities and behavioral contexts: visual (giant fiber escape response, landing response); chemical (proboscis extension reflex, olfactory jump response, locomotory startle response, odor-induced leg response, experience-dependent courtship modification); electric (shock avoidance); and mechanical (leg resistance reflex, cleaning reflex). Each model system shows several of Thompson and Spencer’s [Thompson, R. F., & Spencer, W. A. (1966). Habituation: A model phenomenon for the study of neuronal substrates of behavior. Psychological Review, 73, 16–43] parametric criteria for habituation: spontaneous recovery and dishabituation have been described in almost all of them and dependence of habituation upon stimulus frequency and stimulus intensity in the majority. Stimulus generalization (and conversely, the delineation of stimulus specificity) has given insights into the localization of habituation or the neural architecture underlying sensory processing.The strength of Drosophila for studying habituation is the range of genetic approaches available. Mutations have been used to modify specific neuroanatomical structures, ion channels, elements of synaptic transmission, and second-messenger pathways. rutabaga and dunce, genes of the cAMP signal pathway that have been studied most often in the reviewed experiments, have also been implicated in synaptic plasticity and associative conditioning in Drosophila and other species including mammals. The use of the Gal4/UAS system for targeting gene expression has enabled genetic perturbation of defined sets of neurons. One clear lesson is that a gene may affect habituation differently in different behaviors, depending on the expression, processing, and localization of the gene product in specific circuits. Mutations of specific genes not only provide links between physiology and behavior in the same circuit, but also reveal common mechanisms in different paradigms of behavioral plasticity. The rich repertoire of models for habituation in the fly is an asset for combining a genetic approach with behavioral, anatomical and physiological methods with the promise of a more complete understanding.     

The fear potentiated startle effect. Blink reflex modulation as a result of classical aversive conditioning

A differential conditioning study examined whether an acoustic startle probe, presented during extinction of an aversively conditioned visual stimulus, potentiated the reflex eyeblink response in humans and whether this potentiation varied with the change in affective valence of the conditioned stimulus. Sixty college students were randomly assigned to view a series of two slides, depicting either unpleasant/highly arousing, unpleasant/moderate arousing, neutral/calm, pleasant/moderate arousing or pleasant/highly arousing scenes and objects (duration: 8 sec). During preconditioning (8 trials) and extinction (24 trials) acoustic startle probes (white noise bursts [50 ms; 95 dBA] were administered during and between slide presentation). During acquisition (16 trials) CS+ was reinforced by an electric shock. Startle response magnitudes significantly increased from preconditioning to extinction and were substantially larger to CS+. Conditioned startle reflex augmentation linearly increased with the pleasantness of the slides. Furthermore, subjects showed a greater post-conditioning increase of judged aversiveness to slides that they had previously reported to be more pleasant, exactly paralleling the startle reflex results.     

Startle response and muscular fatigue effects upon fractionated hand grip reaction time

The fractionation of a simple right-hand grip total reaction time (RT) into central and peripheral temporal components (premotor and motor time, respectively) helped to define the site of RT change following an auditory induced startle response and two fatiguing hand-grip exercise regiments for eight males and eight females. Following the startle response, mean values for RT significantly lengthened, due primarily to an increase in premotor time. In contrast, lengthened RT following both fatigue regimens (42% and 55% strength decrements) were due to substantial increases in the motor time component. These results suggest that although performance of tasks which demand a high degree of precision, accuracy, and fine motor control may be disrupted by the introduction of such stressors as an induced startle and local muscular fatigue, the neuromuscular mechanisms mediating performance disruption are dissimilar.     

Social stimuli increase physiological reactivity but not defensive responses

Emotional reactions are crucial in survival because they provide approach and withdrawal behaviors. However, an unsolved question is whether the social content of the affective stimuli has a specific effect on emotional responses. We studied whether the social content of affective pictures influenced the defensive response and response mobilization. For this purpose, we recorded startle blink reflex (a defensive response) and skin conductance responses (a measure of unspecific physiological reactivity or arousal) in 73 participants while they viewed a series of 81 pictures of varying affective valence and social content. Our results revealed that defense response, as indicated by increases in the magnitude of the startle blink reflex, was mainly dependent on threatening or unpleasant cues, but was unrelated to the social content of the pictures. The social content, however, had an influence on pleasant stimuli, provoking an increase in resource mobilization, as reflected by changes in electrodermal activity. Hence, the social content of the affective stimuli may increase the physiological arousal elicited by pleasant stimuli, and it appears to be unrelated to the defense reactivity provoked by unpleasant stimuli.