N-methyl-D-aspartate lesions of the lateral and basolateral nuclei of the amygdaloid block fear-potentiated startle and shock sensitization of startle.

Destroyed cell bodies in the lateral and basolateral amygdaloid nuclei by local infusion of N-methyl-{d}-aspartate. Adjacent areas, such as the central amygdaloid nucleus, were largely spared. Lesions were carried out before training and testing (Exp 1) or after training but before testing (Exp 2). In both cases, the lesions completely blocked fear-potentiated startle (increased acoustic startle in the presence of a light previously paired with footshock). They also blocked increased startle after a series of footshocks, provided they damaged the most anterior part of the basolateral nucleus. It is suggested that the lateral or basolateral amygdaloid nuclei (or both) relay visual information to the central amygdaloid nucleus, which is also critical for fear-potentiated startle. In addition, activation of the most anterior part of the basolateral nucleus may be critical for processing shock information during fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of NMDA receptors within the amygdala in short- versus long-term memory for fear conditioning as assessed with fear-potentiated startle.

Pretraining intra-amygdala infusions of the NMDA receptor antagonist, D,L-AP5, block fear-potentiated startle in rats tested 24+ hr after training. This may reflect a failure of either acquisition or retention. To evaluate these alternatives, rats were tested for fear-potentiated startle during fear conditioning (30 light-shock pairings [0.6 mA shock]), as well as 1–30 min and 48 hr after fear conditioning. Amygdala lesions abolishes fear-potentiated startle at all train-test intervals. Intra-amygdala AP5 infusions (25 nmol/side) abolished fear-potentiated startle during the long-term test and had partial effects at shorter train-test intervals. When the level of fear-potentiated startle during the short-term test was lowered to that of the 48-hr test (i.e., by training rats with a lower, 0.3 mA footshock), AP5 abolished fear-potentiated startle at each timepoint. Thus, amygdala NMDA receptors appear to participate in the initial acquisition of fear memories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intra-amygdala infusion of the N-methyl-D-aspartate receptor antagonist AP5 blocks acquisition but not expression of fear-potentiated startle to an auditory conditioned stimulus.

The fear-potentiated startle paradigm, in which the amplitude of the startle reflex is enhanced in the presence of a stimulus previously paired with footshock, was used to measure aversive conditioning after intra-amygdala infusion of the competitive N-methyl-{d}-aspartate (NMDA) receptor antagonist {dl}-2-amino-5-phosphonopentanoic acid (AP5). Infusion of 2.5 μg/side AP5 immediately before 5 noise–footshock pairings on each of 2 consecutive days dose-dependently blocked acquisition or consolidation of auditory fear-potentiated startle, consistent with previous results obtained with a visual stimulus. Somatosensory or auditory transmission deficits do not appear to be induced by intra-amygdala AP5, because rats reacted normally to footshocks and showed reliable potentiated startle expression after pretesting AP5 infusion at a dose that blocked acquisition. Together with earlier reports, these data suggest that an NMDA-dependent process localized in or near the amygdala may be necessary for the acquisition of conditioned fear across different sensory modalities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus": Correction to McNish et al (2000).

Reports an error in "Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus" by Kenneth A. McNish, Jonathan C. Gewirtz and Michael Davis (Behavioral Neuroscience, 2000[Feb], Vol 114[1], 64-76). The captions for Figure 4 (p. 70) and Figure 5 (p. 72) were printed incorrectly. The caption used for Figure 4 should appear under Figure 5, and the caption used for Figure 5 should appear under Figure 4. (The following abstract of the original article appeared in record 2000-13470-005.) The role of the dorsal hippocampus in contextual fear conditioning was investigated with a contextual blocking paradigm. In Experiment 1, rats were given pairings of a light conditioned stimulus (CS) and footshock after preexposure either to footshock or to the context alone. The group preexposed to footshock showed poorer fear conditioning to the light CS, as measured by the fear-potentiated startle reflex. In Experiment 2, a group preexposed to footshock in the same context showed poorer fear conditioning to the light CS than did a group preexposed to footshock in a different context, indicating contextual blocking of fear-potentiated startle. In Experiment 3, lesions of the dorsal hippocampus had no effect on contextual blocking, even though contextual freezing was disrupted. The sparing of contextual blocking indicated that contextual memory was intact following hippocampal lesions, despite the disruption of contextual freezing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Desflurane and the nonimmobilizer 1,2-dichlorohexafluorocyclobutane suppress learning by a mechanism independent of the level of unconditioned stimulation

We previously demonstrated that anesthetics and non-immobilizers suppress learning and memory in rats. In the training portion of the test, rats received a light plus a footshock and learned to associate the two, as evidenced by subsequent potentiation of the response (jumping) to light plus a noise (fear-potentiated startle). However, anesthetics and nonimmobilizers also decreased the response of animals receiving footshocks during training, which suggests that the reduction in fear-potentiated startle might reflect analgesia, rather than an impairment of learning and memory. Furthermore, although we previously demonstrated that the nonimmobilizer 2,3-dichlorohexafluorocyclobutane (2N) could completely abolish learning, we did not demonstrate the minimal dose required. In the present study, we eliminated analgesia as a confounding factor by training rats breathing desflurane and 2N with footshock intensities that produced responses at least equal to those produced in control animals. Both desflurane and 2N suppressed learning at 0.2 times the minimum alveolar anesthetic concentration (MAC) or the MAC predicted from lipid solubility, despite the increased footshock intensity. This partial pressure of desflurane equals that previously shown to suppress learning at lower footshock intensities. We conclude that suppression of learning and memory by desflurane and 2N does not result from decreased sensitivity to the unconditioned stimulus (the footshock) and that the potency of 2N is consistent with its lipophilicity. IMPLICATIONS: General anesthesia eliminates recall of intraoperative events, including pain. Using an animal model, we refuted the hypothesis that lack of recall results from the analgesia (i.e., the reduced response to painful stimuli produced by inhaled drugs) rather than from a direct effect on learning.     

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)     

Footshock-induced sensitization of electrically elicited startle reflexes.

Acoustic startle is a short-latency reflex mediated by a neural circuit consisting of the ventral cochlear nucleus (VCN), ventral nucleus of the lateral lemniscus (VLL), the nucleus reticularis pontis caudalis (RPC), and the spinal cord. The present study sought to determine the point along this pathway where footshocks might ultimately alter neural transmission to affect startle response. Rats were implanted bilaterally with stimulating electrodes in either the VCN, VLL, or RPC. Startle could be elicited acoustically with a noise burst or electrically with a single-pulse stimulus to either the VCN, VLL, or RPC before and after a train of ten 0.6-mA, 500-ms shocks presented at a rate of 1 shock/s. Startle elicited acoustically or electrically in the VCN or VLL was significantly elevated following shocks. Data suggest that footshock sensitization ultimately alters transmission in the startle circuit at the RPC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus.

[Correction Notice: An erratum for this article was reported in Vol 114(2) of Behavioral Neuroscience (see record 2007-17251-001). The captions for Figure 4 (p. 70) and Figure 5 (p. 72) were printed incorrectly. The caption used for Figure 4 should appear under Figure 5, and the caption used for Figure 5 should appear under Figure 4.] The role of the dorsal hippocampus in contextual fear conditioning was investigated with a contextual blocking paradigm. In Experiment 1, rats were given pairings of a light conditioned stimulus (CS) and footshock after preexposure either to footshock or to the context alone. The group preexposed to footshock showed poorer fear conditioning to the light CS, as measured by the fear-potentiated startle reflex. In Experiment 2, a group preexposed to footshock in the same context showed poorer fear conditioning to the light CS than did a group preexposed to footshock in a different context, indicating contextual blocking of fear-potentiated startle. In Experiment 3, lesions of the dorsal hippocampus had no effect on contextual blocking, even though contextual freezing was disrupted. The sparing of contextual blocking indicated that contextual memory was intact following hippocampal lesions, despite the disruption of contextual freezing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory-Mediated Fear Conditioning in Mice: Simultaneous Measurements of Fear-Potentiated Startle and Freezing.

This study demonstrates that mice display olfactory-cued fear as measured with both freezing and fear-potentiated startle. Following a preconditioning test to measure any unconditioned responses to odor, mice received 5 pairings of a 10-s odor with a 0.25-s, 0.4-mA footshock. The next day, startle and freezing were measured in the presence and absence of the odor. Both fear measures increased after training with amyl acetate (Experiment 1) and acetophenone (Experiment 2). The enhancement of startle did not occur when the same number of odors and shocks were presented in an unpaired fashion (Experiment 3). Furthermore, mice were able to discriminate between an odor paired with shock and a nonreinforced odor (Experiment 4). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sensitization of the startle reflex by footshock: Blockade by lesions of the central nucleus of the amygdala or its efferent pathway to the brainstem.

Bilateral electrolytic lesions of the central, but not the lateral, nucleus of the amgydala blocked shock sensitization of startle (the increase in startle produced by presentation of ten 0.6-mA footshocks in rapid succession). Lesions of the central nucleus also decreased reactivity to shock (jumping and flinching) during shock presentation. However, this decrease in reactivity cannot account for the blockade of shock sensitization, because when a higher shock intensity (1.0 mA) was used, producing equivalent reactivity to that of controls at 0.6 mA, central nucleus lesions still blocked shock sensitization. Moreover, lesions of the caudal part of the ventral amygdalofugal pathway, which carries central nucleus efferents to the startle reflex pathway, also blocked shock sensitization. It is hypothesized that shock activates the central nucleus of the amygdala, which increases startle through modulation of the startle pathway. Activation of the amygdala by shock may be the unconditioned response relevant for fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cocaine enhances the expression of fear-potentiated startle: Evaluation of state-dependent extinction and the shock-sensitization of acoustic startle.

Cocaine's effects on fear extinction and on the shock-sensitization of acoustic startle were examined. Following fear acquisition, rats exposed to the nonreinforced CS after cocaine administration demonstrated significant levels of fear-potentiated startle when evaluated in the drug-free state. The CS also increased startle amplitudes in subjects extinguished and tested with cocaine, indicating that mechanisms other than state-dependent learning are involved in the extinction deficit. The presentation of 10 footshocks augmented acoustic startle, and the shock enhancement was unaffected by cocaine preexposure. These data indicate that the aversive consequences of footshock relevant to the acquisition of conditional fear are not sensitized by the drug. It was suggested that cocaine reinforces fear responding to a threatening stimulus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence of contextual fear after lesions of the hippocampus: a disruption of freezing but not fear-potentiated startle

The roles of the dorsal hippocampus and the central nucleus of the amygdala in the expression of contextual fear were assessed using two measures of conditioned fear: freezing and fear-potentiated startle. A discriminable context conditioning paradigm was developed that demonstrated both conditioned freezing and fear-potentiated startle in a context paired previously with foot shock, relative to a context in which foot shock had never been presented. Post-training lesions of the central nucleus of the amygdala completely blocked both contextual freezing and fear-potentiated startle. Post-training lesions of the dorsal hippocampus attenuated contextual freezing, consistent with previous reports in the literature; however, these same lesions had no effect on fear-potentiated startle, suggesting preserved contextual fear. These results suggest that lesions of the hippocampus disrupt the freezing response but not contextual fear itself.     

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.     

Lesions of the perirhinal cortex interfere with conditioned excitation but not with conditioned inhibition of fear.

Posttraining lesions of the perirhinal cortex (Prh) have been shown to interfere with the expression of fear. This study assessed whether Prh lesions would also disrupt the inhibition of fear as measured with conditioned inhibition of fear-potentiated startle. Following light + shock, noise→ light-no shock conditioned-inhibition training, rats were given Prh lesions. The lesions interfered with the expression of fear-potentiated startle to the light. To assess whether conditioned inhibition was affected, the rats were given light + retraining without additional noise→ light - training. The noise-conditioned inhibitor retained its ability to inhibit fear-potentiated startle to the retrained light. These results suggest that the areas of the Prh that are essential for the initial expression of conditioned fear are not important for the expression of conditioned inhibition of fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the Dorsal Hippocampus Block Trace Fear Conditioned Potentiation of Startle.

Several studies show that the hippocampus is critical for the memories mediating trace and contextual fear conditioning. This study investigates whether N-methyl-D-aspartate-induced lesions of the dorsal hippocampus made prior to training affect context fear conditioning and trace fear conditioning measured with the fear-potentiated startle. Pretraining excitotoxic lesions of the dorsal hippocampus blocked acquisition of trace fear conditioning to a tone stimulus but did not affect context fear conditioning. These data indicate that without a dorsal hippocampus rats are unable to acquire trace conditioning but can acquire contextual fear when fear is measured by potentiation of the startle response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lack of a temporal gradient of retrograde amnesia in rats with amygdala lesions assessed with the fear-potentiated startle paradigm.

It is well known that lesions of the hippocampal formation produce a temporally graded retrograde amnesia for certain types of memory. A similar pattern of results has been reported with amygdaloid lesions in avoidance learning (K. C. Liang et al, 1982). The present study examined the effects of posttraining amygdaloid lesions using a Pavlovian conditioning task, fear-potentiated startle, in which the amplitude of the acoustic startle reflex is increased when elicited in the presence of a cue (e.g., a light) previously paired with footshock. Electrolytic lesions of the amygdala given either 6 or 30 days after training blocked the expression of potentiated startle, indicating no temporal gradient of amnesia over these intervals in this test paradigm. The effects of amygdaloid lesions on different measures of aversive learning are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Olfactory-mediated fear-potentiated startle.

Recently, R. Richardson, A. Vishney, and J. Lee (1999) reported that ambient odor cues that were previously paired with footshock potentiate the acoustic startle response in rats. The authors of the present study extend those findings by using a discrete 4-s amyl acetate odor paired with footshock to address several parametric issues that might be important for using odorants as conditioned stimuli (CSs) in this paradigm. Amyl acetate (5%) had no significant effect on startle in untrained rats but did potentiate startle in rats that received 1, 2, 5, or 10 odor-shock pairings. Fear-potentiated startle decreased but was still significant up to 40 days after conditioning and could be measured in test trials separated by as little as 30 s. The magnitude of potentiated startle decreased with decreasing concentrations of amyl acetate (5%-5 x 10-9%). The anxiolytic compound buspirone (10 mg/kg) significantly attenuated olfactory-mediated fear-potentiated startle. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fear-potentiated startle in two strains of inbred mice.

The fear-potentiated startle paradigm has been used with great success to examine conditioned fear in both rats and humans. The purpose of this study was to examine fear-potentiated startle in inbred mice. One-month-old C57BL/6J (C57) and DBA/2J (DBA) mice were given tone?+?foot shock training trials. The amplitude of the acoustic startle reflex was measured in the presence and absence of the tone both before and after training. Both strains showed fear-potentiated startle after training as evidenced by larger startle amplitudes in the presence of the tone than in its absence. However, the magnitude of fear-potentiated startle was greater in DBA mice than in C57 mice. These results not only demonstrate fear-potentiated startle in mice for the first time but also suggest that fear-potentiated startle can be influenced by characteristics of the mouse strain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrolytic lesions of the amygdala block acquisition and expression of fear-potentiated startle even with extensive training but do not prevent reacquisition.

Lesions of the amygdala have been shown to block the expression of fear-potentiated startle (increased acoustic startle in the presence of a cue previously paired with shock). In the present study, bilateral lesions of the central nucleus of the amygdala given after extensive training totally blocked the expression of fear-potentiated startle but did not prevent reacquisition. In contrast, when the lesions were made before any training, the lesioned rats did not show potentiated startle even with extensive training. Thus, the central nucleus of the amygdala normally seems to be required for the initial acquisition and expression of potentiated startle regardless of the degree of learning. However, reacquisition of potentiated startle can occur without the central nucleus, which implies the presence of a secondary brain system that can compensate for the loss of the central nucleus of the amygdala under some circumstances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)