Dual Effects of Limbic Seizures on Psychosis-Relevant Behaviors Shown by Nucleus Accumbens Kindling in Rats

Ma, Jingyi; Leung, L. Stan

doi:10.1016/j.brs.2016.05.006

Cited by 14 publications

(8 citation statements)

References 52 publications

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“…This focus on the NAC has been substantiated by numerous subsequent reports, and 30+ years later, the NAC remains a crucial structure in current models for the regulation and dysregulation of PPI (e.g. Bikovsky et al, 2016; Ma and Leung, 2016; Vadnie et al, 2016). But a key concept introduced by our 1992 review was that of a regulation of PPI by inter-connected CSPT circuitry – of which the NAC was one component – and which accessed pontine startle circuitry via descending efferent projections from the ventral pallidum into the pedunculopontine nucleus (PPTg; hence cortico-striato-pallido-pontine, or ‘CSPP’ circuitry); it was this latter structure, we proposed, that served to transmit the regulatory ‘tone’ established within the forebrain circuit to the primary startle circuit, and thereby alter the inhibitory impact of the lead stimulus (prepulse) on the startle reflex.…”

Section: Theme 2: Limbic Cspp Circuitry Regulates Ppimentioning

confidence: 84%

Sensorimotor gating of the startle reflex: what we said 25 years ago, what has happened since then, and what comes next

2016

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Our 1992 paper, ‘The neural substrates of sensorimotor gating of the startle reflex: a review of recent findings and their implications’, reviewed a series of (then) new and preliminary findings from cross-species studies of prepulse inhibition of the startle reflex, and commented on their implications. At the time that the report was composed, PubMed listed about 40 citations for studies using the search term ‘prepulse inhibition’. In the ensuing 25 years, the field has added about 2700 such reports, reflecting the substantial growth in interest in prepulse inhibition and its utility across a number of different experimental applications. The 30th anniversary of the Journal of Psychopharmacology provides an opportunity to comment briefly on what was described in that 1992 report, how the field has progressed in the subsequent decades, and the paths forward for studies of prepulse inhibition and its use as an operational measure of sensorimotor gating. Among these future paths, we highlight the use of prepulse inhibition as: an endophenotype for genomic studies, and a biomarker for healthy brain circuitry, which may predict sensitivity to psychotherapeutics. Our 1992 report was highly speculative and based on paper-thin empirical data, yet viewed in a certain light, it appears to have contained a basic roadmap for a journey spanning the next 25 years of prepulse inhibition research… and ‘what a long, strange trip it’s been’.

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Section: Theme 2: Limbic Cspp Circuitry Regulates Ppimentioning

confidence: 84%

Sensorimotor gating of the startle reflex: what we said 25 years ago, what has happened since then, and what comes next

2016

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“…The PPI deficits in GEPR-3s may be related to the same underlying pathology as the anxiety-like behaviors as serotonin modulates PPI in rodents ( 93 , 94 ), and human studies report disrupted PPI in patients with panic disorder ( 95 , 96 ). However, while kindling epileptogenesis disrupts PPI ( 97 , 98 ), GAERs display either normal or facilitated PPI depending on the age tested ( 99 ), suggesting that PPI deficits are not a universal comorbidity of seizures in animal models.…”

Section: Discussionmentioning

confidence: 99%

Genetically Epilepsy-Prone Rats Display Anxiety-Like Behaviors and Neuropsychiatric Comorbidities of Epilepsy

et al. 2018

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Epilepsy is associated with a variety of neuropsychiatric comorbidities, including both anxiety and depression. Despite high occurrences of depression and anxiety seen in human epilepsy populations, little is known about the etiology of these comorbidities. Experimental models of epilepsy provide a platform to disentangle the contribution of acute seizures, genetic predisposition, and underlying circuit pathologies to anxious and depressive phenotypes. Most studies to date have focused on comorbidities in acquired epilepsies; genetic models, however, allow for the assessment of affective phenotypes that occur prior to onset of recurrent seizures. Here, we tested male and female genetically epilepsy-prone rats (GEPR-3s) and Sprague-Dawley controls in a battery of tests sensitive to anxiety-like and depressive-like phenotypes. GEPR-3s showed increased anxiety-like behavior in the open field test, elevated plus maze, light-dark transition test, and looming threat test. Moreover, GEPR-3s showed impaired prepulse inhibition of the acoustic startle reflex, decreased sucrose preference index, and impaired novel object recognition memory. We also characterized defense behaviors in response to stimulation thresholds of deep and intermediate layers of the superior colliculus (DLSC), but found no difference between strains. In sum, GEPR-3s showed inherited anxiety, an effect that did not differ significantly between sexes. The anxiety phenotype in adult GEPR-3s suggests strong genetic influences that may underlie both the seizure disorder and the comorbidities seen in epilepsy.

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“…Ma, Boyce, and Leung () found that mu opioid receptors in the nucleus accumbens mediate immediate postictal decrease in locomotion after an amygdaloid kindled seizure in rats. Jingyi Ma et al demonstrated that electrical kindling of the NAc resulted in convulsive seizure on animal models of psychosis (Ma and Leung, ). Zhou et al showed that high frequency stimulation of the shell of the NAc significantly prolonged the latency to develop seizures, suppressed the severity of seizures, and reduced the second stage and total duration of seizures using pilocarpine‐induced rodent models.…”

Section: Discussionmentioning

confidence: 99%

Connectivity‐based parcellation of the nucleus accumbens into core and shell portions for stereotactic target localization and alterations in each NAc subdivision in mTLE patients

Zhao

Yang

Wang

et al. 2017

Human Brain Mapping

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The nucleus accumbens (NAc), an important target of deep brain stimulation for some neuropsychiatric disorders, is thought to be involved in epileptogenesis, especially the shell portion. However, little is known about the exact parcellation within the NAc, and its structural abnormalities or connections alterations of each NAc subdivision in temporal lobe epilepsy (TLE) patients. Here, we used diffusion probabilistic tractography to subdivide the NAc into core and shell portions in individual TLE patients to guide stereotactic localization of NAc shell. The structural and connection abnormalities in each NAc subdivision in the groups were then estimated. We successfully segmented the NAc in 24 of 25 controls, 14 of 16 left TLE patients, and 14 of 18 right TLE patients. Both left and right TLE patients exhibited significantly decreased fractional anisotropy (FA) and increased radial diffusivity (RD) in the shell, while there was no significant alteration in the core. Moreover, relatively distinct structural connectivity of each NAc subdivision was demonstrated. More extensive connection abnormalities were detected in the NAc shell in TLE patients. Our results indicate that neuronal degeneration and damage caused by seizure mainly exists in NAc shell and provide anatomical evidence to support the role of NAc shell in epileptogenesis. Remarkably, those NAc shell tracts with increased connectivities in TLE patients were found decreased in FA, which indicates disruption of fiber integrity. This finding suggests the regeneration of aberrant connections, a compensatory and repair process ascribed to recurrent seizures that constitutes part of the characteristic changes in the epileptic network.

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Dual Effects of Limbic Seizures on Psychosis-Relevant Behaviors Shown by Nucleus Accumbens Kindling in Rats

Cited by 14 publications

References 52 publications

Sensorimotor gating of the startle reflex: what we said 25 years ago, what has happened since then, and what comes next

Sensorimotor gating of the startle reflex: what we said 25 years ago, what has happened since then, and what comes next

Genetically Epilepsy-Prone Rats Display Anxiety-Like Behaviors and Neuropsychiatric Comorbidities of Epilepsy

Connectivity‐based parcellation of the nucleus accumbens into core and shell portions for stereotactic target localization and alterations in each NAc subdivision in mTLE patients

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