Nitric oxide modulates dopaminergic regulation of prepulse inhibition in the basolateral amygdala

2010 ◽  
Vol 25 (12) ◽  
pp. 1639-1648 ◽  
Author(s):  
C Salum ◽  
AC Issy ◽  
ML Brandão ◽  
FS Guimarães ◽  
EA Del Bel
Keyword(s):  
Nitric Oxide ◽  
Prepulse Inhibition ◽  
Basolateral Amygdala ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Sensorimotor Gating ◽  
Disruptive Effect ◽  
Sound Pulse ◽  
Systemic Injection ◽  
Local Inhibition

Systemic injection of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (LNO) prevents the disruptive effect of amphetamine (Amph) on prepulse inhibition (PPI), a sensorimotor gating model in which the amplitude of the acoustic startle response (ASR) to a startling sound (pulse) is reduced when preceded immediately by a weaker stimulus (prepulse). Given that dopamine (DA) projections to the basolateral amygdala (BLA) are involved in the control of information processing, our aim was to investigate if intra-BLA administration of LNO would modify the disruption caused by the DA agonists, Amph, apomorphine (Apo) and quinpirole (QNP), on PPI. Male Wistar rats received bilateral intra-BLA microinjections (0.2 µL/min/side) of combined treatments (saline or LNO 11 µg followed by saline, QNP 3 µg, Apo 10 µg or Amph 30 µg). PPI was disrupted by intra-BLA Apo, QNP or Amph but not by LNO. Prior bilateral intra-BLA injection of LNO prevented the Apo- and QNP-induced disruption of PPI but did not affect that caused by Amph. APO- or QNP-induced increases in ASR to prepulse + pulse were also restored by LNO. Since local inhibition of NO formation affected the effects of direct, but not indirect, DA agonists, the results suggest that this modulation is not occurring at the level of DA release but may involve complex interactions with other neurotransmitter systems.

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 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.

scholarly journals Genetic Determinants of Gating Functions: Do We Get Closer to Understanding Schizophrenia Etiopathogenesis?

2020 ◽  
Vol 11 ◽  
Author(s):  
Rastislav Rovný ◽  
Dominika Besterciová ◽  
Igor Riečanský
Keyword(s):  
Prepulse Inhibition ◽  
Association Studies ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Genetic Association Studies ◽  
Sensorimotor Gating ◽  
Sensory Gating ◽  
Eligibility Criteria ◽  
Level Of Evidence ◽  
Sensory Stimuli

Deficits in the gating of sensory stimuli, i.e., the ability to suppress the processing of irrelevant sensory input, are considered to play an important role in the pathogenesis of several neuropsychiatric disorders, in particular schizophrenia. Gating is disrupted both in schizophrenia patients and their unaffected relatives, suggesting that gating deficit may represent a biomarker associated with a genetic liability to the disorder. To assess the strength of the evidence for the etiopathogenetic links between genetic variation, gating efficiency, and schizophrenia, we carried out a systematic review of human genetic association studies of sensory gating (suppression of the P50 component of the auditory event-related brain potential) and sensorimotor gating (prepulse inhibition of the acoustic startle response). Sixty-three full-text articles met the eligibility criteria for inclusion in the review. In total, 117 genetic variants were reported to be associated with gating functions: 33 variants for sensory gating, 80 variants for sensorimotor gating, and four variants for both sensory and sensorimotor gating. However, only five of these associations (four for prepulse inhibition—CHRNA3 rs1317286, COMT rs4680, HTR2A rs6311, and TCF4 rs9960767, and one for P50 suppression—CHRNA7 rs67158670) were consistently replicated in independent samples. Although these variants and genes were all implicated in schizophrenia in research studies, only two polymorphisms (HTR2A rs6311 and TCF4 rs9960767) were also reported to be associated with schizophrenia at a meta-analytic or genome-wide level of evidence. Thus, although gating is widely considered as an important endophenotype of schizophrenia, these findings demonstrate that evidence for a common genetic etiology of impaired gating functions and schizophrenia is yet unsatisfactory, warranting further studies in this field.

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

Structural brain correlates of prepulse inhibition of the acoustic startle response in healthy humans

NeuroImage ◽  
2005 ◽  
Vol 26 (4) ◽  
pp. 1052-1058 ◽  
Author(s):  
Veena Kumari ◽  
Elena Antonova ◽  
Elizabeth Zachariah ◽  
Adrian Galea ◽  
Ingrid Aasen ◽  
...  
Keyword(s):  
Prepulse Inhibition ◽  
Startle Response ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Healthy Humans ◽  
Brain Correlates ◽  
Structural Brain
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