scholarly journals Behavioural consequences of Setd1a haploinsufficiency in mice: evidence for heightened emotional reactivity and impaired sensorimotor gating

2021 ◽  
Author(s):  
Matthew L. Bosworth ◽  
Anthony R. Isles ◽  
Lawrence S. Wilkinson ◽  
Trevor Humby
Keyword(s):  
Neurodevelopmental Disorders ◽  
Emotional Reactivity ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Sensorimotor Gating ◽  
Neural Systems ◽  
Loss Of Function ◽  
Methyl Transferase ◽  
Genes Encoding ◽  
Histone Methyl Transferase

ABSTRACTA number of studies implicate the loss of function (LoF) mutations affecting the histone methyl transferase SETD1A in the aetiology of a range of neurodevelopmental disorders including schizophrenia. Here, we examined the behavioural consequences of haploinsufficiency of Setd1a in a mouse model. We find evidence for changes in a number of phenotypes of relevance to schizophrenia, including increased anxiety-related behaviour, enhanced acoustic startle response, and decreased pre-pulse inhibition of acoustic startle. The sensorimotor gating deficits in Setd1a+/- mice could not be rescued by haloperidol or risperidone, suggesting that these antipsychotics are ineffective for ameliorating schizophrenia-relevant phenotypes in Setd1a+/- mice and point to deficits in neural systems other than the monoamine system. These phenotypes are emerging as key features of a number of other mouse models of rare neurodevelopmental disorders caused by LoF mutations in genes encoding epigenome modifiers suggesting they may act in a network to modulate brain development. Taken together these data strengthen the support for the use of Setd1a haploinsufficient mice as a model for the biological basis of schizophrenia, and point towards possible underpinning neural mechanisms.

Impaired sensorimotor gating of the acoustic startle response in the prodrome of schizophrenia

2008 ◽  
Vol 23 ◽  
pp. S70 ◽  
Author(s):  
B.B. Quednow ◽  
I. Frommann ◽  
J. Berning ◽  
K.U. Kühn ◽  
W. Maier ◽  
...  
Keyword(s):  
Startle Response ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Sensorimotor Gating

scholarly journals Inhibition of the Deep and Intermediate Layers of the Superior Colliculus Disrupts Sensorimotor Gating in Monkeys

2020 ◽  
Vol 14 ◽  
Author(s):  
Hannah F. Waguespack ◽  
Brittany L. Aguilar ◽  
Ludise Malkova ◽  
Patrick A. Forcelli
Keyword(s):  
Superior Colliculus ◽  
Startle Response ◽  
Basolateral Amygdala ◽  
Rhesus Macaques ◽  
Species Difference ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Sensorimotor Gating ◽  
Intermediate Layers ◽  
Association Area

The deep and intermediate layers of the superior colliculus (DLSC) respond to visual, auditory, and tactile inputs and act as a multimodal sensory association area. In turn, activity in the DLSC can drive orienting and avoidance responses—such as saccades and head and body movements—across species, including in rats, cats, and non-human primates. As shown in rodents, DLSC also plays a role in regulating pre-pulse inhibition (PPI) of the acoustic startle response (ASR), a form of sensorimotor gating. DLSC lesions attenuate PPI and electrical stimulation of DLSC inhibits the startle response. While the circuitry mediating PPI is well-characterized in rodents, less is known about PPI regulation in primates. Two recent studies from our labs reported a species difference in the effects of pharmacological inhibition of the basolateral amygdala and substantia nigra pars reticulata (SNpr) on PPI between rats and macaques: in rats, inhibition of these structures decreased PPI, while in macaques, it increased PPI. Given that the SNpr sends direct inhibitory projections to DLSC, we next sought to determine if this species difference was similarly evident at the level of DLSC. Here, we transiently inactivated DLSC in four rhesus macaques by focal microinfusion of the GABAA receptor agonist muscimol. Similar to findings reported in rodents, we observed that bilateral inhibition of the DLSC in macaques significantly disrupted PPI. The impairment was specific to the PPI as the ASR itself was not affected. These results indicate that our previously reported species divergence at the level of the SNpr is not due to downstream differences at the level of the DLSC. Species differences at the level of the SNpr and basolateral amygdala emphasize the importance of studying the underlying circuitry in non-human primates, as impairment in PPI has been reported in several disorders in humans, including schizophrenia, autism, and PTSD.

scholarly journals Psychophysiological correlates of personality factors of impulsive aggression in subjects with personality disorders and in mentally healthy subjects

2020 ◽  
Vol 13 (1) ◽  
pp. 107-121
Author(s):  
K.Yu. Telesheva ◽  
Z.I. Storozheva ◽  
V.V. Myamlin ◽  
A.V. Kirenskaya ◽  
F.S. Safuanov
Keyword(s):  
Personality Disorders ◽  
Acoustic Startle ◽  
Control Level ◽  
Acoustic Startle Response ◽  
Sensorimotor Gating ◽  
Personality Factors ◽  
Control Group ◽  
Impulsive Aggression ◽  
Psychophysiological Correlates ◽  
External Stimuli

The comparative study of sensorimotor gating in the model of acoustic startle response (ASR) and personal traits was provided in mentally healthy offenders (24 s.) and offenders with personal disorders (15 s.) accused of crimes committed by the mechanism of impulsive aggression (IA) was provided. The control group consisted of 39 healthy male volunteers. The battery of psychometric techniques was applied, notably questionnaires of Spielberger, Rusalov’s structure of temperament questionnaire, Rotter’s modified version of the subjective control level assessment, Zuckerman and Buss-Durkee questionnaires. The basic ASR measures and prepulse modification were analyzed. Significantly different IA mechanisms were found in the groups of offenders at both the psychological and neurobiological level. It has been shown that, in individuals with personality disorders, the IA is based on the propensity to realize their own aggressive intentions or motivations, which, apparently, acquires a self-contained motivating value regardless of external stimuli. The important role of emotional factors in the mechanisms of impulsive aggressive reactions was shown in the mentally healthy offenders.

scholarly journals Clerodendrum inermeLeaf Extract Alleviates Animal Behaviors, Hyperlocomotion, and Prepulse Inhibition Disruptions, Mimicking Tourette Syndrome and Schizophrenia

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hon-Lie Chen ◽  
Hsin-Jung Lee ◽  
Wei-Jan Huang ◽  
Jui-Feng Chou ◽  
Pi-Chuan Fan ◽  
...  
Keyword(s):  
Tourette Syndrome ◽  
Prepulse Inhibition ◽  
Therapeutic Potential ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Sensorimotor Gating ◽  
Ethanol Extract ◽  
Channel Blockers ◽  
Mk 801 ◽  
Animal Behaviors

Previously, we found a patient with intractable motor tic disorder, a spectrum of Tourette syndrome (TS), responsive to the ground leaf juice ofClerodendrum inerme(CI). Here, we examined the effect of the ethanol extract ofCIleaves (CIextract) on animal behaviors mimicking TS, hyperlocomotion, and sensorimotor gating deficit. The latter is also observed in schizophrenic patients and can be reflected by a disruption of prepulse inhibition of acoustic startle response (PPI) in animal models induced by methamphetamine and NMDA channel blockers (ketamine or MK-801), based on hyperdopaminergic and hypoglutamatergic hypotheses, respectively.CIextract (10–300 mg/kg,i.p.) dose-dependently inhibited hyperlocomotion induced by methamphetamine (2 mg/kg,i.p.) and PPI disruptions induced by methamphetamine, ketamine (30 mg/kg,i.p.), and MK-801 (0.3 mg/kg,i.p.) but did not affect spontaneous locomotor activity, rotarod performance, and grip force. These results suggest thatCIextract can relieve hyperlocomotion and improve sensorimotor gating deficit, supporting the therapeutic potential ofCIfor TS and schizophrenia.

Alterations in brainstem auditory processing, the acoustic startle response and sensorimotor gating of startle in Wistar audiogenic rats (WAR), an animal model of reflex epilepsies

2020 ◽  
Vol 1727 ◽  
pp. 146570
Author(s):  
Alexandra Olimpio Siqueira Cunha ◽  
Marzieh Moradi ◽  
Junia Lara de Deus ◽  
Cesar Celis Ceballos ◽  
Nikollas Moreira Benites ◽  
...  
Keyword(s):  
Animal Model ◽  
Auditory Processing ◽  
Startle Response ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Sensorimotor Gating
Sign in / Sign up

Export Citation Format

Share Document