Visual pathways involved in fear conditioning measured with fear-potentiated startle: behavioral and anatomic studies.
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Visual pathways to the amygdala, a brain structure critical for classical fear conditioning, were investigated. Conditioned fear was measured in rats as increased acoustic startle amplitude in the presence versus absence of a light or an odor paired previously with foot shock (fear-potentiated startle). Post-training lesions of both the lateral geniculate body (LG) and lateral posterior nucleus (LP) of the thalamus together, but not lesions of LG or LP alone, completely blocked the expression of fear-potentiated startle to a visual conditioned stimulus (CS) but not to an olfactory CS. These lesions also did not block contextual fear conditioning using startle or freezing as measures. Local infusion of 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f] quinoxaline-7-sulfonamide disodium, an AMPA antagonist, into the visual thalamus immediately before testing also blocked fear-potentiated startle to a visual CS, suggesting that the lesion effects were not attributable to damage of fibers of passage. Iontophoretic injections into the LP of the anterograde tracer biotinylated dextran amine resulted in heavy anterograde labeling in two amygdala-fugal cortical areas: area TE2 and dorsal perirhinal cortex (PR), and moderate labeling in the lateral amygdaloid nucleus (L). These results suggest that, during classical fear conditioning, a visual stimulus can be transmitted to the amygdala via either lemniscal (i.e., LG --> V1, V2 --> TE2/PR) or non-lemniscal (i.e., LP --> V2, TE2/PR) thalamo-cortico-amygdala pathways, or direct thalamo-amygdala (i.e., LP --> L) projections. (+info)
Enhanced affective startle modulation in salt-sensitive subjects.
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Salt-sensitive normotensive men exhibit an enhanced pressor response to mental stress. Although an enhanced pressor response is associated with higher affective startle modulation in men, an association between salt sensitivity of blood pressure and affective startle modulation has not been studied so far. We studied reactivity to mental stress and startle modulation in 14 salt-sensitive healthy white male students and 14 salt-resistant control subjects, who were well matched for age, body mass index, physical fitness, and family history of hypertension. Subjects performed a computerized information-processing task under time pressure (manometer test), while heart rate and blood pressure were continuously registered. In a separate session, subjects viewed a series of 42 pictures of the International Affective Picture System (IAPS), varying in pleasure and arousal, while acoustic startle probes were administered randomly, and electromyogram activity of the orbicular eye muscle was continuously recorded. Startle modulation was calculated as the difference between startle responses under negative and positive affective stimuli. In contrast to salt-resistant subjects, salt-sensitive subjects showed significantly enhanced startle amplitudes under negative stimuli and diminished amplitudes under positive stimuli. Thus, salt-sensitive subjects displayed a significantly higher startle modulation than did salt-resistant subjects (P<0.05). Subjective ratings of the presented IAPS pictures did not differ between the groups. The increased startle modulation of salt-sensitive subjects suggests an enhanced activity of the central nucleus of the amygdala. This enhanced central nervous responsiveness may contribute to higher sympathetic pressor reactivity and, thus, to the later development of hypertension in salt-sensitive individuals. (+info)
A new mouse model with cochleo-saccular type inner ear defects.
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We found a new inner ear mutant exhibiting abnormal behavior, such as circling and head shaking, in a breeding stock of SJL/J mice. The traits are inherited in a simple autosomal-recessive fashion. Animals homozygous for the responsible gene, designated cosa, show no startle response to sounds and an inability to swim. In the inner ears of cosa/cosa homozygous, but not +/cosa heterozygous adults, histopathological features of severe damage that are typical for 'cochleo-saccular' or 'spotting' mutants have been demonstrated. We suggest here that the abnormal mice carry a mutation of a gene that is developmentally switched on in the early stages of development and is involved in endolymph homeostasis. (+info)
Spontaneous arousal activity in infants during NREM and REM sleep.
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The infant arousal response involves subcortical and cortical responses occurring as a sequence of stereotyped behaviour regardless of the eliciting stimulus. The spontaneous activity of these responses during sleep, however, is uncertain. We examined the spontaneous arousal pattern in normal infants to determine the sequence of responses, and to examine their periodicity and the effects of sleep state. We performed a nap polysomnographic study on 10 normal infants between 2 and 10 weeks of age. Electroencephalographic and electro-oculographic activity, and respiratory airflow and movements were measured, and video recordings were made throughout each study. Different levels of arousal behaviour were examined. We found that spontaneous arousal activity occurred frequently and the majority of responses occurred as a sequence involving an augmented breath followed by a startle and then cortical arousal. Subcortical arousals as reflected by augmented breaths and startles were more common than cortical arousals. Additionally, augmented breaths followed by apnoea were recorded and were not usually associated with other arousal responses. All of the responses occurred periodically either as bursts of activity or as isolated responses. Each of the responses occurred more frequently during rapid eye movement (REM) sleep than during non-rapid eye movement (NREM) sleep. We conclude that there is an endogenous rhythm of spontaneous activity in infants involving excitatory processes from the brainstem, which may or may not be closely followed by cortical excitation. The spontaneous arousal responses occur periodically but with a high level of irregularity and the level of activity is affected by sleep state. (+info)
A mutation (V260M) in the middle of the M2 pore-lining domain of the glycine receptor causes hereditary hyperekplexia.
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We investigated the molecular basis of hyperekplexia (STHE), an inherited neurological disorder characterised by neonatal hypertonia and an exaggerated startle response, in a kindred and identified a novel missense mutation in the pore-lining M2 domain of the alpha1 subunit of the glycine receptor (GLRA1). Sequencing analysis of all exons of the GLRA1 gene revealed a G1158A base transition in affected, heterozygous patients. The base transition results in a valine to methionine substitution at codon 260 in the middle of the M2 transmembrane domain. The location within the M2 domain suggests for this substitution a likely role in altering ion channel properties. (+info)
Prenatal immune challenge disrupts sensorimotor gating in adult rats. Implications for the etiopathogenesis of schizophrenia.
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Increasing evidence associates schizophrenia with prenatal exposure to infection. Impaired ability to "gate out" sensory and cognitive information is considered to be a central feature of schizophrenia and is manifested, among others, in disrupted prepulse inhibition (PPI) of the acoustic startle reflex. We analyzed the effect of a prenatal immune challenge- peripheral administration of bacterial endotoxin lipopolysaccharide (LPS) to pregnant female rats-upon PPI and immune function in adult offspring. Prenatal LPS treatment disrupted PPI which was reversed by antipsychotics. Serum levels of interleukin-2 and interleukin-6 were increased. In addition, histopathological features in brain areas related with PPI circuitry were observed. These results illustrate the critical influence of prenatal immune events upon adult CNS functioning in association with the putative role of the immune system in the etiopathogenesis of schizophrenia. (+info)
Depletion of 5-HT disrupts prepulse inhibition in rats: dependence on the magnitude of depletion, and reversal by a 5-HT precursor.
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The 5-HT(1A) agonist 8-OH-DPAT has been reported to disrupt prepulse inhibition (PPI) of the acoustic startle reflex after local administration into the raphe nuclei. Because it is likely that 8-OH-DPAT disrupted PPI by activation of somatodendritic inhibitory receptors, and thereby, via a decrease in 5-HT neurotransmission, we tested whether chronic, drug-induced, depletions of 5-HT have similar effects. Rats were drug-treated for three consecutive days and tested in a short PPI paradigm on day 4, and retested 2 h later, after acute saline or drug administration. Repeated treatment with the 5-HT synthesis inhibitor p-chlorophenylalanine methyl ester (PCPA; 160 mg/kg) produced a small, but significant, attenuation of PPI, and a large decrease in extracellular 5-HT levels in the hippocampus, as measured in independent microdialysis experiments. An even larger depletion of 5-HT was obtained by substituting the 3(rd) PCPA administration with the 5-HT releaser d-fenfluramine (10 mg/kg); this combined treatment nearly abolished PPI in the majority of animals. The involvement of 5-HT in the latter effects was confirmed by the finding that low doses of the 5-HT precursor 5-hydroxy-L-tryptophan reinstated PPI during retest. These data, together with recently published studies, provide strong evidence that pharmacologically-induced depletion of 5-HT disrupts PPI. (+info)
Nociceptive quality of the laser-evoked blink reflex in humans.
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Laser radiant-heat pulses selectively excite the free nerve endings in the superficial layers of the skin and activate mechano-thermal nociceptive afferents; when directed to the perioral or supraorbital skin, high-intensity laser pulses evoke a blink-like response in the orbicularis oculi muscle (the laser blink reflex, LBR). We investigated the functional properties (startle or nociceptive origin) of the LBR and sought to characterize its central pathways. Using high-intensity CO(2)-laser stimulation of the perioral or supraorbital regions and electromyographic (EMG) recordings from the orbicularis oculi muscles, we did five experiments in 20 healthy volunteers. First, to investigate whether the LBR is a startle response, we studied its habituation to expected rhythmic stimuli and to unexpected arrhythmic stimuli. To assess its possible nociceptive quality, we studied changes in the LBR and the R2 component of the electrical blink reflex after a lidocaine-induced supraorbital nerve block and after intramuscular injection of the opiate fentanyl and the opiate-antagonist naloxone. To characterize the central pathways for the LBR, we investigated the interaction between the LBR and the three components of the blink reflex (R1, R2, and R3) by delivering laser pulses to the perioral or supraorbital regions before or after electrical stimulation of the supraorbital nerve at various interstimulus intervals. Finally, to gain further information on the central LBR pathways, using two identical CO(2)-laser stimulators, we studied the LBR recovery curves with paired laser pulses delivered to adjacent forehead points at interstimulus intervals from 250 ms to 1.5 s. The LBR withstood relatively high-frequency rhythmic stimulations, and unexpected laser pulses failed to evoke larger responses. When lidocaine began to induce hypoalgesia (about 5 min after the injection), the LBR was abolished, whereas R2 was only partly suppressed 10 min after the injection. Fentanyl injection induced strong, naloxone-reversible, LBR suppression (the response decreased to 25.3% of predrug values at 10 min and to 4% at 20 min), whereas R2 remained appreciably unchanged. Whether directed to the perioral or supraorbital regions, preceding laser pulses strongly suppressed R2 and R3 though not R1. Conversely, preceding electrical stimuli to the supraorbital nerve suppressed the LBR. In response to paired stimuli, the LBR recovered significantly faster than R2. These findings indicate that the LBR is a nociceptive reflex, which shares part of the interneuron chain mediating the nonnociceptive R2 blink reflex, probably in the medullary reticular formation. The LBR may prove useful for studying the pathophysiology of orofacial pain syndromes. (+info)