Sensitization of the acoustic startle reflex by footshock.

Administration of footshock (500-ms duration, 0.2–2.4 mA) increased the amplitude of the startle reflex for a long time after its presentation. The effect occurred with a single footshock, although its magnitude and consistency across animals were greater with 5 or 10 footshocks presented 1/s. The facilitatory effect came on within 2–4 min with a 0.6-mA shock, peaking in about 10 min and then dissipating over the next 40 min. Stronger shocks also increased startle, but with a more delayed onset of facilitation (8–20 min). Footshocks increased startle in rats not previously given startle-eliciting stimuli, indicating sensitization rather than dishabituation. The facilitatory effect may not be attributable to a rapid conditioning to the experimental context, because a change in lighting conditions from shock presentation to testing did not attenuate shock sensitization. This excitatory effect of shock on startle may represent the unconditioned effect of shock that can become associated with a neutral stimulus to support classical fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of amygdala central nucleus lesions on blocking and unblocking.

The effects of lesions of the amygdala central nucleus (CN) on blocking and unblocking of appetitive Pavlovian conditioning were examined in 2 experiments with rats. In both lesioned and unlesioned rats, prior pairing of one CS with a food unconditioned stimulus/stimuli (UCS) blocked the acquisition of conditioning to a 2nd CS when a compound of both stimuli was paired with that same UCS. If the value of the UCS was increased or decreased when the 2nd CS was added, unlesioned rats acquired substantial conditioning to the 2nd cue (unblocking). Unblocking occurred in lesioned rats only when the UCS value was increased. In both lesioned and unlesioned rats, unblocking was prevented if the compound cue was paired with the original UCS prior to the change in UCS value. These data suggest that the CN is involved in increasing attention to signals for significant events but not in tuning out redundant cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sensitization of the rat startle response by noise.

In a series of 6 experiments with a total of 160 male Sprague-Dawley albino rats, it was found that the startle response showed a progressive increase in amplitude when tones were presented against a high level of background noise. This sensitization effect was not a result of repetitive exposure to tones but rather a result of continuous exposure to noise. The size of the effect was directly related to noise intensity and required about 30-45 min to reach a maximum. The effect did not dissipate when the noise was maintained but did dissipate once the noise was turned down. Results are discussed in terms of the experimental conditions under which repetitive stimulus exposure produces either sensitization or habituation of the startle reflex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Norepinephrine release in the amygdala after systemic injection of epinephrine or escapable footshock: contribution of the nucleus of the solitary tract

Several findings based largely on lesions and drug manipulations within the amygdala suggest that norepinephrine (NE) systems in the amygdala contribute to enhancement of memory processes by epinephrine (EPI). However, no studies to date have directly measured changes in the release of NE in the amygdala after EPI injection. In Experiment 1, in vivo microdialysis was used to assess amygdala NE release after systemic injection of saline, EPI (0.1 or 0.3 mg/kg), and administration of an escapable footshock (0.8 mA, 1 s). Both doses of EPI produced a significant elevation in NE release that persisted for up to 60 min. In Experiment 2, the local anesthetic lidocaine (2%) was infused (0.5 microl) into the nucleus of the solitary tract (NTS) immediately before injection of 0.3 mg/kg EPI. The EPI-induced elevation in amygdala NE release observed in Experiment I was attenuated by inactivation of the NTS. These findings indicate that systemic injection of EPI increases release of NE in the amygdala and suggest that the effects are mediated in part by activation of brainstem neurons in the NTS that project to the amygdala.     

Inhibitory learning tests of conditioned stimulus associability in rats with lesions of the amygdala central nucleus.

Normal rats showed faster inhibitory learning about a light conditioned stimulus (CS) if it had previously been an inconsistent predictor of a tone CS than if it had been a consistent predictor of the tone. In contrast, the inhibitory learning of rats with ibotenic acid lesions of the amygdala central nucleus (CN) was unaffected by the prior predictive value of the light. These results support claims that the CN is critical to surprise-induced enhancement of attentional processing of CSs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Goal-directed responding is sensitive to lesions to the prelimbic cortex or basolateral nucleus of the amygdala but not to their disconnection.

The current view of instrumental conditioning indicates that performance in the early stage of training is maintained by a representation of the outcome, as indexed by its sensitivity to changes in the value of the reward. In the present study, the authors tested the effects of a disconnection of the prelimbic cortex (PL) and the basolateral nucleus of the amygdale (BLA), using an asymmetric lesion procedure, to determine whether these structures interact sequentially as part of a corticolimbic system. In marked contrast to the effects of bilateral lesions of the PL or the BLA, which both altered rats' sensitivity to outcome devaluation, the disconnection of these 2 brain areas was without an effect on outcome devaluation. These results demonstrate that the PL and the BLA mediate different aspects of outcome representation in goal-directed responding. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear

The amplitude of the acoustic startle response is reliably enhanced when elicited in the presence of bright light (light-enhanced startle) or in the presence of cues previously paired with shock (fear-potentiated startle). Light-enhanced startle appears to reflect an unconditioned response to an anxiogenic stimulus, whereas fear-potentiated startle reflects a conditioned response to a fear-eliciting stimulus. We examine the involvement of the basolateral nucleus of the amygdala, the central nucleus of the amygdala, and the bed nucleus of the stria terminalis in both phenomena. Immediately before light-enhanced or fear-potentiated startle testing, rats received intracranial infusions of the AMPA receptor antagonist 2, 3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)-quinoxaline (3 microg) or PBS. Infusions into the central nucleus of the amygdala blocked fear-potentiated but not light-enhanced startle, and infusions into the bed nucleus of the stria terminalis blocked light-enhanced but not fear-potentiated startle. Infusions into the basolateral amygdala disrupted both phenomena. These findings indicate that the neuroanatomical substrates of fear-potentiated and light-enhanced startle, and perhaps more generally of conditioned and unconditioned fear, may be anatomically dissociated.     

Enhancement of acoustic startle by electrical stimulation of the amygdala.

The present study demonstrated that electrical stimulation of the amygdala enhanced the acoustic startle response. A 25-ms train of 0.1-ms pulses initiated 5 ms before the onset of a 20-ms noise burst significantly increased startle at currents from 40 to 400 μA. Electrode placements just medial to the amygdala (in the pathway connecting the amygdala to the brain stem) increased startle with the lowest currents. Startle was also increased in all animals with stimulation in the central, medial, and intercalated nuclei of the amygdala. Stimulation in areas surrounding the amygdaloid complex was ineffective. In a second experiment, paired pulses with interpulse intervals between 0.1 and 20.0 ms delivered to the amygdala demonstrated that the stimulated axons had a distribution of refractory periods between 0.6 and 1.0 ms. This suggests that the population of neurons which subserves the enhancement of acoustic startle is fairly homogeneous and has small, myelinated axons. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory bulbectomy enhances sensitization of the acoustic startle reflex produced by acute or repeated stress.

The effects of olfactory bulbectomy on the acoustic startle reflex and shock-induced sensitization of the startle reflex were examined in 3 experiments. In Experiment 1, bulbectomized animals showed a modest increase in baseline startle responding following surgery, and normal acquisition of fear-potentiated startle, but a pronounced increase in baseline startle responding during the course of conditioning relative to sham-operated controls. In Experiments 2 and 3, bulbectomized animals showed shock-induced sensitization of the startle reflex to shock intensities that did not produce sensitization in sham and unoperated controls. These data suggest that olfactory bulbectomy results in an increased vulnerability to stressors, which may be mediated by a disinhibition of the amygdala or other structures involved in mediating stress and anxiety. Thus, the olfactory bulbectomy model of depression may share some similarities with other stress-induced models of depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modulation of the acoustic startle reflex by infusion of corticotropin-releasing hormone into the nucleus reticularis pontis caudalis

The amplitude of the acoustic startle reflex can be modulated by exposure to aversive stimuli or other conditions which evoke a state of fear. The neurotransmitters involved in this modulation are currently being investigated. Unilateral local infusion of corticotropin-releasing hormone (CRH; 0, 10, 20, 40 and 80 ng) into the nucleus reticularis pontis caudalis (PnC), an obligatory synapse in the acoustic startle reflex, significantly elevated startle amplitude in a dose-dependent manner. The facilitation of startle began immediately following infusion, reached asymptote approximately 20-25 min later, and persisted throughout the remaining 60 min test session. This CRH-enhanced startle effect was blocked by infusion of the CRH antagonist, alpha-helical CRH9-41, immediately prior to CRH infusion. These results support an involvement of CRH at the level of the PnC in modulating the acoustic startle reflex.     

Lesions of the central nucleus of the amygdala block conditioned excitation, but not conditioned inhibition of fear as measured with the fear-potentiated startle effect.

Lesions of the amygdala block the expression of fear-potentiated startle following either moderate or extensive light?+?shock training. The present experiment assessed whether lesions of the amygdala would also block the expression of conditioned inhibition of fear. Rats were given conditioned inhibition training in which a light was paired with shock and a noise and light compound was presented in the absence of shock. Then half of the rats were given bilateral electrolytic lesions of the amygdala and the remaining rats were sham operated. Lesions of the amygdala blocked the expression of fear-potentiated startle to the light. To assess whether conditioned inhibition was disrupted, rats were retrained with light?+?shock pairings with no further conditioned inhibition training. Amygdala lesioned rats reacquired fear-potentiated startle to the light (Kim & Davis, 1993). Importantly, the noise conditioned inhibitor retained its ability to inhibit fear-potentiated startle to the retrained light. These results indicate that areas of the amygdala critical for initial performance of fear-potentiated startle are not critical for the expression of conditioned inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Augmentation of the rat's acoustic startle reflex by nonreflexogenic stimuli.

The size of the rat's acoustic startle reflex was augmented by brief acoustic clicks (which did not themselves elicit startle) presented several milliseconds before the reflex-eliciting stimulus (RS). The same clicks presented after the RS gave relatively weak augmentation that was present in the 1st, but not the 2nd, testing session. Brief footshocks set to 75% of each animal's flinch threshold augmented startle when presented both before and after the RS in both testing sessions. Augmentation by a leading footshock increased with shock intensity and also with the intensity of the RS. Augmentation by a trailing footshock increased with shock intensity and also with the intensity of the RS. Reflex size is not fixed at the time of reflex elicitation but can be augmented by a later nonreflexogenic stimulus. Reflex augmentation may be caused by the 2nd member of a stimulus pair discharging elements of the reflex pathway that were partially activated by the 1st. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibition of acoustic startle in the rat by a footshock prestimulus: Effects of morphine and naloxone.

Investigated the ability of footshock to inhibit the rat's acoustic startle response. Based on the mean thresholds obtained from a flinch-jump test, 8 rats were tested in a startle inhibition procedure with prestimulus intensities of 0.1, 0.2, 0.4, and 0.8 mA. Ss were presented with a series of startle-eliciting noise bursts, preceded by a 300-ms footshock of one of the four intensities. Control trials consisting of the noise alone were also included. Startle amplitude was measured during the 100 ms immediately following the noise onset. Footshock reliably inhibited startle at all intensities; inhibition was near maximum at 0.2 mA. Morphine administration reliably interfered with the inhibition at all intensities, and this was reversed by naloxone administration. Data suggest that morphine may have a more general effect than is currently believed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the central nucleus of the amygdala in olfactory heart rate conditioning.

The role of the central nucleus of the amygdala on olfactory heart rate conditioning in the infant rat was investigated. The conditioned stimulus (CS) consisted of a 10-s presentation of grape juice odor that was immediately followed by a 0.5-s, 0.35-mA subcutaneous shock. A sensitization control group was also run. Three days prior to testing, Ss received either bilateral electrolytic lesions of the central nucleus of the amygdala, sham lesions, or were left unperturbed. Results show that damage to the central nucleus of the amygdala severely impaired olfactory heart rate conditioning but that it had no deleterious effect on the heart rate orienting response to that stimulus or on the heart rate unconditioned response (UCR) to shock. Results are analogous to those in previous research on auditory heart rate conditioning and suggest that the central nucleus of the amygdala may constitute a necessary stage in the transduction of the CS into a cardiac conditioned response (CR) regardless of sensory modality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the amygdala, but not of the cerebellum or red nucleus, block conditioned fear as measured with the potentiated startle paradigm.

In Exp I, 97 male Sprague-Dawley albino rats were given 10 light–shock pairings on 2 successive days. At 24–48 hrs following training, groups of Ss received bilateral transection of the cerebellar peduncles, bilateral lesions of the red nucleus (which receives most of the cerebellar efferents), or bilateral lesions of the central nucleus of the amygdala. Controls were sham operated. At 3–4 days after surgery, Ss were tested for potentiated startle (PS [increased acoustic startle in the presence of the light previously paired with shock]). PS was blocked by lesions of the central nucleus of the amygdala but not by transection of the cerebellar peduncles or lesions of the red nucleus. Exp II, in which a visual prepulse test was used with 14 Ss, indicated that the blockade of PS observed in Ss with amygdala lesions could not be attributed to optic tract damage. Exp III, with 20 Ss, demonstrated that the absence of potentiation in Ss with amygdala lesions was not simply due to a lowered startle level ceiling, because these Ss could show increased startle with increased stimulus intensity and with administration of intraperitoneal strychnine, (0.75 mg/kg), a drug that increases startle. Results are consistent with the hypothesis that the amygdala is involved in fear conditioning. (64 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of reward timing information on cue associability are mediated by amygdala central nucleus.

The central nucleus of the amygdala (CeA) has been implicated in a range of associative learning phenomena often attributed to changes in attentional processing of events. Experiments using a number of behavioral tasks have shown that rats with lesions of CeA fail to show the enhancements of stimulus associability that are normally induced by the surprising omission of expected events. By contrast, in other tasks, rats with lesions of CeA show normal enhancements of associability when events are presented unexpectedly. In this experiment, we examined the effects of CeA lesions on changes in cue associability in a reward timing task. In sham-lesioned rats, the associability of cues that were followed by stimuli that provided reward timing information was maintained at higher levels than that of cues that were followed by uninformative stimuli. Rats with lesions of CeA failed to show this advantage. These results indicate that the role of CeA in the modulation of associability is not limited to cases of event omission. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Operant and Pavlovian control of visual stimulus orienting and food-related behaviors in rats with lesions of the amygdala central nucleus.

The effects of superimposing operant reward and omission contingencies on 2 Pavlovian conditioned responses evoked by a visual conditioned stimulus paired with food were examined in rats with lesions of the amygdala central nucleus (CN). In sham-lesioned rats, the frequency of an orienting response, rearing, was increased by reward contingencies and decreased by omission contingencies, compared with yoked Pavlovian controls. In contrast, in CN-lesioned rats, rearing was not affected by either operant contingency and occurred at lower levels with Pavlovian procedures alone than in sham-lesioned rats. Nevertheless, CN-lesioned and sham-lesioned rats showed similar increases in the frequency of conditioned food-cup behavior with reward contingencies, similar decreases with omission contingencies, and similar levels of that response with Pavlovian procedures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prepulse inhibition of acoustic startle in rats after lesions of the pedunculopontine tegmental nucleus.

Prepulse inhibition (PPI) of startle is impaired in schizophrenics, which suggests they have disturbances in circuitry that controls PPI. How activity in forebrain circuitry is communicated to the primary startle circuit to modulate PPI was explored. Subpallidal cells innervate the pedunculopontine tegmental nucleus (PPTg). Infusion of the γ-aminobutyric acid antagonist picrotoxin into the subpallidum impaired PPI. In other rats, electrolytic PPTg lesions decreased or eliminated PPI, potentiated startle amplitude, and did not alter habituation. The disruption of PPI correlated significantly with the extent of PPTg damage. PPTg lesions reduced PPI when startle stimuli were weak or intense (104 or 140 db) and when prepulse stimuli ranged from 2 to 17 db above background but were most profound with prepulses 5–8 db above background. The PPTg modulates sensorimotor gating and may process and transmit information from forebrain structures to the primary startle curcuit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the bed nucleus of the stria terminalis block sensitization of the acoustic startle reflex produced by repeated stress, but not fear-potentiated startle

1. The effects of lesions of the bed nucleus of the stria terminalis (BST) on the acquisition of conditioned fear were examined. In Experiment 1, BST lesions did not block acquisition of fear-potentiated startle to an explicit visual conditioned stimulus (CS) over 20 days of training. However, BST lesions blocked a gradual elevation in baseline startle also seen over the course of training. 2. The gradual increase in baseline startle was replicated in Experiment 2 without the presence of an explicit CS, using unoperated subjects. Experiment 2 showed that the elevation was due to repetitive exposure to shock, because unshocked control subjects did not show any elevation over sessions. 3. In Experiment 3, lesions of the BST did not disrupt rapid sensitization of the startle reflex by footshock, showing that different neural substrates underlie sensitization of startle by acute and chronic exposure to footshock. 4. These data indicate that the BST, despite its anatomical continuity with the amygdala, is not critically involved in the acquisition of conditioned fear to an explicit CS. Nevertheless, the BST is involved in mediating a stress-induced elevation in the startle reflex. This suggests that the BST and the CeA, which constitute part of the "extended amygdala" have complementary roles in responses to stress.     

Attention and schizophrenia: Impaired modulation of the startle reflex.

The startle reflex (SR) elicited by abrupt stimuli can be modified by attention to nonstartling stimuli that shortly precede the startle-eliciting stimulus. The present study of 15 recent-onset, relatively asymptomatic schizophrenic outpatients and 14 demographically matched normal control Ss demonstrated that attentional modulation of SR is impaired in schizophrenic patients. Specifically, the control group exhibited greater startle eye-blink modification following to-be-attended prestimuli than following to-be-ignored prestimuli, whereas the patients failed to show the attentional modulation effect. These results suggest traitlike attentional deficits in schizophrenia because the patients were relatively asymptomatic. The measurement of attentional modulation of SR may provide a nonverbal, reflexive, state-independent marker of the vulnerability to schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)