SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
The effects of acute and chronic ethanol intake on the startle response was examined in male rats. Ethanol given IP produced a dose-dependent decrease in the amplitude of the startle response measured 30 min later. With a dose of 1 g/kg, the effect was evident at 15 min and had recovered substantially by 60 min. The effect of ethanol on the startle response was potentiated by pretreatment of the animals with pimozide, haloperidol, and p-chlorophenylalanine but not by propranolol, phenoxybenzamine, alpha-methyltyrosine, or pargyline. After 3 weeks on an ethanol-containing diet, the startle response was greater than that shown by rats on the control iso-caloric, sucrose-containing diet. After ethanol withdrawal, the startle response was further increased, with a peak about 9 to 12 hr after discontinuation of ethanol; thereafter, the response declined. This time course of heightened startle response during ethanol withdrawal corresponds to the time course of the activation of noradrenergic neurons during withdrawal. It appears that dopaminergic and serotonergic neurons are involved in the mediation of the startle response in rats.
In a series of 6 experiments the effects of p-chloroamphetamine (PCA) on the acoustic startle response in rats were investigated. 15 min after 5 mg/kg PCA startle amplitude was inhibited, 2-15 hr after PCA startle was facilitated. Rate of habituation however was not altered. Both the inhibitory and excitatory effects of PCA were blocked by pretreatment with p-chlorophenylalanine but not by alpha-methyl-p-tyrosine. 24 hr, 1 week and 4 weeks after PCA, initial startle amplitude was unchanged but PCA increased rate of sensitization over successive tone blocks. Increased sensitization was most pronounced at 10 mg/kg and absent at 2.5 mg/kg. The early inhibitory effect of PCA but not the later facilitatory effect was eliminated by reducing the level of background noise. The results suggest that inhibition of startle sensitization is associated with enhanced release of serotonin (5-HT) whereas enhancement of startle sensitization is associated with 5-HT depletion.
The EMG pattern of startle reactions in the leg was studied in man using a 100 msec, 1 kc/sec squre wave tone burst of 114 dB as the auitory stimulus. At rest, 74 responses were recorded in the ankle flexor tibialis anterior (TA) and 23 in the ankle extensor gastrocnemius (G) with a significantly different mean latency of 151 and 123 msecrespectively. During tonic extension or flexion of the ankle, the EMG response in TA or G consisted in a burst of activity superimposed on the voluntary EMG at a latency of approximately 150 msec after the onset of the tone burst and followed, at 200 msec, by a period of EMG silence lasting close to 100 msec. Similar periods of silence also occurred as the sole EMG modulation in response to sound. Although predominant in flexors, startle reactions are significant in extensors during or after tonic ankle extension suggesting that audiospinal influences may be channelled to one or the other group depending on their functional state. The silent period of EMG following an excitatory startle or appearing on its own suggests an important inhibitory component in audiospinal mechanisms particularly related to startle since it had not been disclosed in a previous study of the modulation of the H-reflex by non-startling auditory stimulus. From the distribution and EMG pattern of startle, it is inferred that audiospinal influences may be meaningfully integrated through the reticulospinal system in sound guided behaviour.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
This paper reviews experiments that have revealed distinct differences between the dorsal and median raphe nuclei in the rat midbrain. The raphe nuclei appear to be hetrogeneous with respect to their anatomical projections to the forebrain, their relevance to specific behaviors, and their pharmacological responses. Startle response measures are useful indicators of the functional state of serotonergic system originating in the median raphe. As a way to study individual cells within the various raphe nuclei, microspectroflurimetric techniques are promising.
Integrated EMG recordings have been used to study the eyeblink component of the human startle reflex. They have shown that the response, to either an auditory or a painful stimulus, consists of an initial excitation followed by a more prolonged period during which a second stimulus, of the same or different sensory modality, fails to evoke a response, or evokes one which is reduced in amplitude. The period of reduced responsiveness does not follow voluntary or spontaneous eyeblinks. Increasing the duration of the startle evoking stimulus has little effect on the excitatory component of the response, but prolongs the subsequent period of reduced responsiveness. When stimuli of one modality are presented repetitively to the subject, the eyeblink response is habituated; the response to a subsequent testing stimulus, of a different sensory modality, is then smaller than that evoked by the testing stimulus alone, but greater than that evoked by the testing stimulus when it follows a single conditioning stimulus. It is concluded that the excitatory and inhibitory components of the startle reflex are at least partially separable and that stimulus novelty has some significance in eliciting a response.
Genetic variation in behavioral traits allows organisms to respond and adapt to environmental challenges. Genetic variation in behavior is often affected by many genes and thus has a complex genetic basis. Inversions, the reorientation of genes along the chromosome, tightly link genetic variants together because they suppress recombination. Therefore, inversions are believed to have a major impact on phenotypic variation because they combine the effects of multiple genes, which can pleiotropically alter multiple aspects of behavior. This study investigates how the inversion In(2L)t, found in Drosophila melanogaster populations around the world, impacts different aspects of behavior in an environment-sensitive manner. We test the activity, foraging, and startle-induced behavior of flies with different In(2L)t genotypes across sex and temperatures. We observe that Drosophila homozygous for In(2L)t sleep less frequently, spend more time away from a food source, and have a longer duration of startle response. Additionally, the impacts of In(2L)t on aspects of behavior can be sex-specific and are largely consistent across temperatures. Taken together, our research demonstrates that inversions can regulate aspects of behavior, and suggests hypotheses explaining the distribution of In(2L)t across space and time.
Discharges of single Purkinje cells in the intermediate and lateral zones of the cerebellar cortex and of neurons in the interpositus and dentate nuclei were recorded in alert monkeys during the presentation of intense auditory and visual stimuli. Concomitant monitoring of the electromyogram (EMG) demonstrated that these stimuli evoked characteristic startle responses in most instances. Firing patterns of cerebellar nuclear cells to auditory stimuli could be categorized into four types, the most common of which consisted of a short-latency acceleration of discharge, followed by a decrease in activity, and in most cells by a later period of facilitation. Simple spike discharge patterns of Purkinje cells consisted largely of prolonged increases or decreases in firing rate, although more complex patterns were seen. In almost 50% of the Purkinje cells tested, complex spikes were evoked by the auditory stimuli. Comparison of simple spike responses of Purkinje cells and of the discharges of cerebellar nuclear cells to auditory and visual inputs revealed that, except for a longer latency, the discharge pattern evoked by flash stimuli was identical to that evoked by sound in all instances. By contrast, in about one-third of the Purkinje cells with related complex spike discharge, complex spikes were evoked by stimuli of only a single modality. Comparison of the times of changes in nuclear and Purkinje cell activity suggests that the initial change in nuclear cell discharge was due to an increase in mossy fiber activity, while the subsequent decrease resulted from Purkinje cell inhibition evoked by mossy and climbing fiber inputs. The absence of increases in nuclear cell discharge at the time of most decreases in Purkinje activity indicates that removal of Purkinje inhibition does not have a major effect on the discharge rates of individual nuclear cells. The data also suggest that excitation of nuclear cells via climbing fiber collaterals played only a minor role in influencing their discharge. Since most EMG changes occurred after or at about the same time as the initial changes in cerebellar discharge, it is unlikely that the initial changes in cerebellar activity were a result of feedback from contracting muscles. It is proposed that the similar discharge patterns of cerebellar neurons to auditory and visual input results from a convergence of these inputs on a structure which projects to the cerebellum as mossy fibers.
Acute ethanol administration decreases cyclic AMP levels in brains of some animal strains. The ethanol-induced decrease of cyclic GMP levels cannot be blocked by intraventricular infusion of calcium but it can be prevented by pretreatment with pyrazole. Although cyclic AMP levels in the cerebral cortex change reciprocally after acute ethanol administration and during withdrawal, the increase observed during withdrawal is probably secondary to some withdrawal processes. Ethanol decreases cerebellar GABA levels only in rats which are stressed prior to sacrifice. Chronic intraventricular infusion of calcium increased the intensity of an acoustic startle response during ethanol withdrawal while EGTA infusion delayed the development of tolerance to the hypothermic effect of ethanol. The ratio of cyclic GMP to GABA levels is postulated to be important for expression of the withdrawal syndrome.
INTRODUCTION: Pathogenic variants in KMT2B cause early-onset dystonia, but a mouse model that has undergone comprehensive, dystonia-oriented phenotyping is lacking. METHODS: We conducted detailed phenotyping on heterozygous Kmt2b constitutive knockout mice and wild-type littermates, assessing growth, neurobehavioural traits, motor coordination, sensorimotor gating, social behaviour and metabolic parameters, combined with striatal RNA sequencing. RESULTS: Kmt2b knockout mice of both sexes were viable but significantly smaller and lighter than littermate controls. Knockouts were hyperlocomotive in the open field and showed approximately two-fold larger acoustic startle responses; unexpectedly, prepulse inhibition was enhanced rather than reduced at all prepulse intensities. On the balance beam, knockouts crossed more slowly and paused more frequently; female knockouts also paused more on the ladder rung task. Frame-by-frame video analysis revealed a claw-like hindpaw posture characterized by abnormal inward flexion of the digits. Knockout mice spent less time investigating a novel conspecific, while social recognition memory remained intact. Striatal RNA sequencing confirmed reduction of Kmt2b transcript to approximately half of control levels and identified 177 differentially expressed genes, including Maob, encoding monoamine oxidase B; gene set enrichment analysis implicated neurodevelopmental, glial and mitochondrial processes. Nociception, vision, body-weight-adjusted grip strength, and clinical chemistry and haematological measures were largely unaffected. CONCLUSION: Heterozygous Kmt2b knockout mice show hyperlocomotion, altered sensorimotor gating, impaired motor coordination with dystonic-like paw posturing and reduced sociability, alongside a striatal transcriptomic signature implicating neurodevelopmental processes. The model mirrors aspects of human KMT2B-related dystonia and provides a platform for mechanistic study; environmental or pharmacological challenge may be needed to unmask overt dystonic features.
Treatment with d-amphetamine produced a dose-dependent increase in startle amplitude in response to a buzzer. This increase appeared to be a reflection of a sensitization effect, i.e., enhanced responsivity as a function of repeated stimulus presentations. Treatment with alpha-methyl-p-tyrosine, which reduced whole brain concentrations of dopamine (DA) and norepinephrine (NE), or treatment with FLA-63, which reduced only NE, antagonized the effects of d-amphetamine on the startle reflex, suggesting a role of NE in this behavior. Startle amplitude was also reduced following chronic d-amphetamine treatment. The effect of d-amphetamine on startle was found to be independent of changes in drug-induced locomotor excitation. The data of the present investigation, together with earlier reports, suggests that tolerance occurs to those behaviors that involve a noradrenergic component.
Large-amplitude waves recorded in the pontine tegmentum, lateral geniculate body and visual cortex herald the onset and continue throughout paradoxical sleep. The role of these ponto-geniculo-occipital (PGO) waves, or spikes, has puzzled researchers since their discovery. This paper reports experiments in cats which have demonstrated that PGO spikes are essentially an epiphenomenon, an electrical sign of the activation of a "startle network" by the neural turmoil of paradoxical sleep. Internal stimulation provided by the bursts of neural activity which characterize paradoxical sleep produces PGO spikes in the lateral geniculate body which are identical in appearance to those elicited during synchronized and paradoxical sleep by 1.55 Hz tone bursts or taps on the cage in normal cats. Cerebellar lesions result in behavioral responses to the intrinsic startles during synchronized sleep in the form of extensor or flexor jerks of the forelimbs. The jerks occur in conjunction with each PGO spike. Identical movements can be induced in the same cats in wakefulness by such startling stimuli as dropping the cat or hissing with an aerosol can. Lesions involving the auditory-visual area permit cats to be stimulated by sound in synchronized sleep without arousal, but anterior lobe lesions produce an easily aroused animal. We postulate that the phenomena observed following cerebellar lesions are the result of alteration in the control of serotonergic neurons of the pontine raphe nuclei.
Facilitation of the learning of a discrimination reversal task for a reward of food was found in rhesus monkeys after subcutaneous administration of a potent pentafluorinated enkephalin analog. (D-Ala2)-F5-Phe4-enkephalin-NH2. General activity, short-term memory, startle, and analgesia, however, were not significantly affected. In a within-subject design, each of 6 monkeys (3 males and 3 females) received each of 5 doses of the enkephalin analog (0.1, 1, 10, 100, and 1,000 microgram/kg). One daily injection was made for 7 consecutive days, including pre- and posttests on the first and last days with the diluent control. The enkephalin doses, with the exception of the 0.1 microgram/kg level, produced significantly faster learning than the diluent. Some sex differences were suggested by the data, but these effects are difficult to interpret. The results suggest that relatively small amounts of this analog given systematically can exert a reliable effect on a complex behavior such as reversal learning at doses devoid of opiate effects, due perhaps to enhanced cognitive flexibility rather than improvement in short-term memory or association formation.
Cats pretreated with morphine (5 mg/kg, IP) received naloxone into the area of the locus coeruleus (LC) or the area of the substantia nigra (SN). The LC-treated animals stopped the morphine-induced stereotyped behavior and showed normal but hyperactive behavior. The SN-treated animals, however, ceased their movements of the head and the forelegs, adopted a rigid posture with extended forelegs and became hypoactive. It is concluded that both the LC area, which contains noradrenergic cell bodies, and the SN area, which contains dopaminergic cell bodies, are sites of action of morphine on behavior.
Explore the source record for details and available documents.
Explore the source record for details and available documents.