Septohippocampal GABAergic neurons mediate the altered behaviors induced by <i>n</i>‐methyl‐<scp>D</scp>‐aspartate receptor antagonists

Ma, Jingyi; Tai, Siew Kian; Leung, L. Stan

doi:10.1002/hipo.22039

Cited by 24 publications

(22 citation statements)

References 69 publications

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“…The net effects of systemic ketamine on CA1-mPFC circuits result from a complex array of direct and indirect actions on glutamatergic neurotransmission, alongside associated disruption of GABAergic, dopaminergic, serotonergic, and/or cholinergic mechanisms (Kapur and Seeman, 2001;Moghaddam, 2003;Ma et al, 2012;Moghaddam and Krystal, 2012). In particular, the 'disinhibition' model of ketamine's actions points to a reduced NMDAR-mediated drive of GABAergic interneurons, which-together with enhanced glutamate release-triggers pyramidal neuron hyperactivity (Homayoun and Moghaddam, 2007).…”

Section: Discussionmentioning

confidence: 99%

Losing Control Under Ketamine: Suppressed Cortico-Hippocampal Drive Following Acute Ketamine in Rats

Moran

Jones

Blockeel

et al. 2014

Neuropsychopharmacol

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Systemic doses of the psychotomimetic ketamine alter the spectral characteristics of hippocampal and prefrontal cortical network activity. Using dynamic causal modeling (DCM) of cross-spectral densities, we quantify the putative synaptic mechanisms underlying ketamine effects in terms of changes in directed, effective connectivity between dorsal hippocampus and medial prefrontal (dCA1-mPFC) cortex of freely moving rats. We parameterize dose-dependent changes in spectral signatures of dCA1-mPFC local field potential recordings, using neural mass models of glutamatergic and GABAergic circuits. Optimizing DCMs of theta and gamma frequency range responses, model comparisons suggest that both enhanced gamma and depressed theta power result from a reduction in top-down connectivity from mPFC to the hippocampus, mediated by postsynaptic NMDA receptors (NMDARs). This is accompanied by an alteration in the bottom-up pathway from dCA1 to mPFC, which exhibits a distinct asymmetry: here, feed-forward drive at AMPA receptors increases in the presence of decreased NMDAR-mediated inputs. Setting these findings in the context of predictive coding suggests that NMDAR antagonism by ketamine in recurrent hierarchical networks may result in the failure of top-down connections from higher cortical regions to signal predictions to lower regions in the hierarchy, which consequently fail to respond consistently to errors. Given that NMDAR dysfunction has a central role in pathophysiological theories of schizophrenia and that theta and gamma rhythm abnormalities are evident in schizophrenic patients, the approach followed here may furnish a framework for the study of aberrant hierarchical message passing (of prediction errors) in schizophrenia-and the false perceptual inferences that ensue.

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Section: Discussionmentioning

confidence: 99%

Losing Control Under Ketamine: Suppressed Cortico-Hippocampal Drive Following Acute Ketamine in Rats

Moran

Jones

Blockeel

et al. 2014

Neuropsychopharmacol

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“…In rats, isolation housing induced a reduction in PPI and action potential height in subicular pyramidal neurons as well as an increase in calretinin-positive neurons in DG, but hippocampal parvalbumin immunoreactivity remained unchanged (Greene et al 2001 ). However, selective lesioning of septohippocampal GABAergic neurons in rats was associated with reduced parvalbumin immunoreactivity in the septal area and an increase in PPI (Ma et al 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Crybb2 coding for βB2-crystallin affects sensorimotor gating and hippocampal function

et al. 2013

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βB2-crystallin (gene symbol: Crybb2/CRYBB2) was first described as a structural protein of the ocular lens. This gene, however, is also expressed in several regions of the mammalian brain, although its function in this organ remains entirely unknown. To unravel some aspects of its function in the brain, we combined behavioral, neuroanatomical, and physiological analyses in a novel Crybb2 mouse mutant, O377. Behavioral tests with male O377 mutants revealed altered sensorimotor gating, suggesting modified neuronal functions. Since these mouse mutants also displayed reduced hippocampal size, we concentrated further investigations on the hippocampus. Free intracellular Ca2+ levels were increased and apoptosis was enhanced in the hippocampus of O377 mutants. Moreover, the expression of the gene encoding calpain 3 (gene symbol Capn3) was elevated and the expression of genes coding for the NMDA receptor subunits was downregulated. Additionally, the number of parvalbumin-positive interneurons was decreased in the hippocampus but not in the cortex of the mutants. High-speed voltage-sensitive dye imaging demonstrated an increased translation of input-to-output neuronal activity in the dentate gyrus of this Crybb2 mutant. These results point to an important function of βB2-crystallin in the hippocampal network. They indicate pleiotropic effects of mutations in the Crybb2 gene, which previously had been considered to be specific to the ocular lens. Moreover, our results are the first to demonstrate that βB2-crystallin has a role in hippocampal function and behavioral phenotypes. This model can now be further explored by future experiments.Electronic supplementary materialThe online version of this article (doi:10.1007/s00335-013-9478-7) contains supplementary material, which is available to authorized users.

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“…Dopamine agent methamphetamine also readily induced psychosis in humans [20,21]. Psychosis relevant behaviors in animals, such as increase in locomotor activities, decrease in PPI and AEP gating was also readily induced by injection of psychotomimetic drugs such as ketamine or MK-801 [22,23].…”

Section: Introductionmentioning

confidence: 99%

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

Leung

2016

Brain Stimulation

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Septohippocampal GABAergic neurons mediate the altered behaviors induced by n‐methyl‐D‐aspartate receptor antagonists

Cited by 24 publications

References 69 publications

Losing Control Under Ketamine: Suppressed Cortico-Hippocampal Drive Following Acute Ketamine in Rats

Losing Control Under Ketamine: Suppressed Cortico-Hippocampal Drive Following Acute Ketamine in Rats

Crybb2 coding for βB2-crystallin affects sensorimotor gating and hippocampal function

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

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