"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)     

Normal conditioning inhibition and extinction of freezing and fear-potentiated startle following electrolytic lesions of medial prefrontal cortex in rats.

The authors investigated the role of medial prefrontal cortex (mPFC) in the inhibition of conditioned fear in rats using both Pavlovian extinction and conditioned inhibition paradigms. In Experiment 1, lesions of ventral mPFC did not interfere with conditioned inhibition of the fear-potentiated startle response. In Experiment 2, lesions made after acquisition of fear conditioning did not retard extinction of fear to a visual conditioned stimulus (CS) and did not impair "reinstatement" of fear after unsignaled presentations of the unconditioned stimulus. In Experiment 3, lesions made before fear conditioning did not retard extinction of fear-potentiated startle or freezing to an auditory CS. In both Experiments 2 and 3, extinction of fear to contextual cues was also unaffected by the lesions. These results indicate that ventral mPFC is not essential for the inhibition of fear under a variety of circumstances. (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 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)     

Peripheral and intraamygdalar administration of the dopamine D? receptor antagonist SCH 23390 blocks fear-potentiated startle but not shock reactivity or the shock sensitization of acoustic startle.

Central dopamine (DA) activity is thought to play a role in fear motivation. The aim of the present study was to assess the involvement of DA D? receptors in emotional learning. The authors report that peripheral and intraamygdalar administration of the specific D? receptor antagonist SCH 23390 blocked the acquisition of fear-potentiated startle. Analysis of shock reactivity during footshock administration revealed that the learning impairment could not be explained by a diminution in the aversive properties of the unconditioned stimulus. Additionally, systemic and intraamygdalar injection of SCH 23390 did not alter fear expression as measured with the shock sensitization of acoustic startle. The potential contribution of mesoamygdaloid DA to the acquisition and retrieval of conditioned fear responses is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Odor-guided fear conditioning in rats: 2. Lesions of the anterior perirhinal cortex disrupt fear conditioned to the explicit conditioned stimulus but not to the training context.

Previous studies examining the neural substrates of fear conditioning have indicated unequivocally that the acquisition and expression of conditioned fear depends critically on the integrity of the amygdala. The extent to which the rhinal cortical areas contribute to fear conditioned to either the explicit conditioned stimulus (CS) or to the training context is less clear, however. The effects of pretraining lesions of the anterior perirhinal (PRH) cortex on fear conditioned to an explicit odor CS and to the context in which CS–unconditioned stimulus pairing took place was examined in rats. Rats with PRH cortex lesions demonstrated a robust attenuation of fear conditioned to the explicit CS, but no attenuation of fear conditioned to the training context. These data suggest that the PRH cortex is an important component of the neural system supporting the association between olfactory cues and footshock and add to a growing body of evidence implicating the rhinal cortical regions in associative learning. (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)     

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)     

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 explicitly 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. (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)     

The effects of cocaine, amphetamine, and the dopamine D1 receptor agonist SKF 38393 on fear extinction as measured with potentiated startle: implications for psychomotor stimulant psychosis

Using Pavlovian conditioned increases in the amplitude of the acoustic startle reflex as a behavioral indicator of fear motivation, the authors previously showed a resistance to extinction after repeated associations of cocaine with the fear-evoking conditioned stimulus (CS). In Experiment 1, acute administration of cocaine, amphetamine, and the dopamine (DA) D1 receptor agonist SKF 38393 produced a similar fear enhancement. In Experiment 2, a noncontingent injection of cocaine and SKF 38393 provoked a CS potentiation of acoustic startle in fear-extinguished laboratory rats. Potential behavioral, neurochemical, and neuroendocrine explanations for the effects of psychomotor stimulants on conditional fear were discussed. It was suggested that DA agonist drugs increase fear expression possibly by activating mesoamygdaloid associative neurocircuitry involved in excitatory conditioned fear reactions.     

Fear conditioning to tone, but not to context, is attenuated by lesions of the insular cortex and posterior extension of the intralaminar complex in rats.

C. Shi and M. Davis (see record 1999-00012-009) recently reported that combined lesions of the posterior extension of the intralaminar complex (PINT) and caudal insular cortex (INS) block acquisition but not expression of fear-potentiated startle to discreet conditioned stimuli (CSs) and a footshock unconditioned stimulus (US) and proposed that PINT-INS projections to the amygdala constitute the essential US pathways involved in fear conditioning. The present study further tested this hypothesis by examining whether PINT-INS lesions block fear conditioning (as measured by freezing) to diffuse-context and discrete-tone CSs, and whether posttraining lesions with continued CS–US training result in extinction to the CSs. Posttraining lesions resulted in a selective attenuation of tone conditoning, but context conditioning was unaffected by pre-and posttraining lesions. These results do not support the view that the PINT-INS represent the essential US pathway in fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posttraining lesions of the amygdala interfere with fear-potentiated startle to both visual and auditory conditioned stimuli in C57BL/6J mice.

The fear-potentiated startle paradigm has been used with great success to examine conditioned fear in both rats and humans. The purpose of the present experiment was to extend the authors' previous findings and further validate the fear-potentiated startle paradigm in mice. In Experiments 1 and 2, C57BL/6J mice were given Pavlovian fear conditioning with either an auditory or a visual conditioned stimulus. Similar to data collected with rats, fear-potentiated startle was observed for both stimulus modalities. In Experiment 3, posttraining lesions of the amygdala disrupted fear-potentiated startle in both conditioned stimulus modalities. These data are consistent with amygdala lesion studies in rats and suggest that fear-potentiated startle in mice requires an intact amygdala. Together, these results extend the authors' previous results and provide the basis for using this well-understood behavioral paradigm for examining the molecular mechanisms of conditioned fear in transgenic and knockout mice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pretraining Inactivation of the Caudal Pontine Reticular Nucleus Impairs the Acquisition of Conditioned Fear-Potentiated Startle to an Odor, but Not a Light.

Recent data from developing rats suggest that structures downstream from the amygdala are involved in the acquisition of conditioned fear-potentiated startle (FPS). The authors tested this idea in adult rats by temporarily inactivating the structure critical for FPS, the caudal pontine reticular nucleus (PnC), during fear conditioning. When the conditioned stimulus (CS) was an odor, rats displayed freezing, but not FPS, at test. This effect was not due to a decrease in footshock sensitivity. Further, no savings were evident on retraining. When the CS was a light, inactivation of the PnC had no effect on the acquisition of FPS. Thus, the PnC may be crucial for the acquisition of conditioned FPS to an odor, but not a light. (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)     

The effects of cocaine, amphetamine, and the dopamine D? receptor agonist SKF 38393 on fear extinction as measured with potentiated startle: Implications for psychomotor stimulant psychosis.

Using Pavlovian conditioned increases in the amplitude of the acoustic startle reflex as a behavioral indicator of fear motivation, the authors previously showed a resistance to extinction after repeated associations of cocaine with the fear-evoking conditioned stimulus (CS). In Experiment 1, acute administration of cocaine, amphetamine, and the dopamine (DA) D? receptor agonist SKF 38393 produced a similar fear enhancement. In Experiment 2, a noncontingent injection of cocaine and SKF 38393 provoked a CS potentiation of acoustic startle in fear-extinguished laboratory rats. Potential behavioral, neurochemical, and neuroendocrine explanations for the effects of psychomotor stimulants on conditional fear were discussed. It was suggested that DA agonist drugs increase fear expression possibly by activating mesoamygdaloid associative neurocircuitry involved in excitatory conditioned fear reactions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contributions of anterior perirhinal cortex to olfactory and contextual fear conditioning

The present experiments examined the effects of excitotoxic lesions of anterior perirhinal cortex (PRH) on the expression of fear conditioned to an explicit olfactory CS and to the context in which CS-US pairing took place. Animals with anterior PRH lesions exhibited an attenuation of fear conditioned to the explicit CS, but no attenuation of fear conditioned to the training context. These data replicate previous findings in our laboratory examining the effects of aspirative lesions of anterior PRH, and are consistent with the notion that this cortical region comprises a critically important component of the neural system mediating the acquisition and/or expression of associations between olfactory cues and footshock.     

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.     

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)     

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)