Impairment of neural coordination in hippocampal neuronal ensembles after a psychotomimetic dose of dizocilpine

Szczurowska, Ewa; Ahuja, Nikhil; Jiruška, Přemysl; Kelemen, Eduard; Stuchlı́k, Aleš

doi:10.1016/j.pnpbp.2017.09.013

Cited by 8 publications

(12 citation statements)

References 54 publications

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“…This disorganized state, marked by a selective increase in co‐activity between previously non‐coactive neurons (hypersynchrony), was also observed in the HPC CA1 and medial PFC (mPFC) after the administration of another NMDAR antagonist phencyclidine (PCP) . In agreement with the discoordination hypothesis, neuronal discoordination induced by NMDAR antagonists was observed without major effects on firing rate in anaesthetized animals or the spatial response properties of neurons in freely moving rats . In addition to pharmacological models based on NMDAR antagonists, unilateral HPC inactivation by the voltage‐dependent Na + channel blocker tetrodotoxin (TTX) also impairs cognitive control in rats and increases coactivity in the uninjected HPC …”

Section: Discoordination In Neuronal Ensemblesmentioning

confidence: 64%

“…Hamm and colleagues used viral transgenic expression of a fluorescent Ca 2+ indicator to compare population activity patterns in the rodent visual cortex after chronic ketamine and in a genetic mouse model (Df A+/− ) of schizophrenia susceptibility. In a striking, parallel to the effect of other NMDAR antagonists (MK‐801, PCP) on immediate‐early gene expression and on electrophysiological neuronal activity in anaesthetized as well as in awake rats, cortical ensemble activity patterns were less distinct and their (re‐)activation was less reliable in both the chronic ketamine and Df A+/− genetic model . In other words, different ensembles were less distinct and similar ensembles were less similar.…”

Section: Discoordination In Neuronal Ensemblesmentioning

confidence: 91%

“…Altered inhibition within the network can lead to an impaired inhibition of firing of neurons outside the active assembly. This would manifest as the hypersynchrony observed by Szczurowska et al and Kao, and result in less stable, shallow attractor states . Multiple classes of interneurons undoubtedly play different roles in the organization of network activity.…”

Section: The Gabaergic System and Excitation/inhibition Disbalance Inmentioning

confidence: 97%

“…Indeed, altered organization of neuronal discharge was observed in models of psychosis and schizophrenia in rats. Dizocilpine (MK‐801), an NMDAR antagonist with psychotomimetic effects, causes the disorganization of temporal discharge of HPC CA1 neurons, so that pairs of neurons that discharged at separate times prior to drug exposure start firing together . This disorganized state, marked by a selective increase in co‐activity between previously non‐coactive neurons (hypersynchrony), was also observed in the HPC CA1 and medial PFC (mPFC) after the administration of another NMDAR antagonist phencyclidine (PCP) .…”

Section: Discoordination In Neuronal Ensemblesmentioning

confidence: 99%

“…If neurons in CA3 and CA1 cannot transmit the input from the DG, the resulting functional deficit may largely recapitulate the dentate‐related impairments. A disorganization of HPC ensemble activity patterns paired with a loss of ensemble code for (spatial) context and impaired cognitive (spatial) coordination on a rotating arena (Carousel) have been observed in CA1 of rats after the systemic NMDAR antagonists PCP and MK‐801 . Aberrant ensemble code for spatial context after systemic MK‐801 was found in rat CA1, but not in CA3 .…”

Section: Discoordination In the Hippocampal Circuitmentioning

confidence: 99%

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Neural and neuronal discoordination in schizophrenia: From ensembles through networks to symptoms

et al. 2019

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Despite the substantial knowledge accumulated by past research, the exact mechanisms of the pathogenesis of schizophrenia and causal treatments still remain unclear. Deficits of cognition and information processing in schizophrenia are today often viewed as the primary and core symptoms of this devastating disorder. These deficits likely result from disruptions in the coordination of neuronal and neural activity. The aim of this review is to bring together convergent evidence of discoordinated brain circuits in schizophrenia at multiple levels of resolution, ranging from principal cells and interneurons, neuronal ensembles and local circuits, to large-scale brain networks. We show how these aberrations could underlie deficits in cognitive control and other higher order cognitive-behavioural functions. Converging evidence from both animal models and patients with schizophrenia is presented in an effort to gain insight into common features of deficits in the brain information processing in this disorder, marked by disruption of several neurotransmitter and signalling systems and severe behavioural outcomes. K E Y W O R D SfMRI, GABA interneurons, humans, oscillations, psychosis, rats

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Section: Discoordination In Neuronal Ensemblesmentioning

confidence: 64%

Section: Discoordination In Neuronal Ensemblesmentioning

confidence: 91%

Section: The Gabaergic System and Excitation/inhibition Disbalance Inmentioning

confidence: 97%

Section: Discoordination In Neuronal Ensemblesmentioning

confidence: 99%

Section: Discoordination In the Hippocampal Circuitmentioning

confidence: 99%

See 3 more Smart Citations

Neural and neuronal discoordination in schizophrenia: From ensembles through networks to symptoms

et al. 2019

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Phencyclidine Disrupts Neural Coordination and Cognitive Control by Dysregulating Translation

Park

Kao

Jourdi

et al. 2024

Biological Psychiatry Global Open Science

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Phencyclidine discoordinates hippocampal network activity but not place fields

Kao

Dvořák

Park

et al. 2017

Preprint

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38We used the psychotomimetic phencyclidine (PCP) to investigate the relationships between 39 cognitive behavior, coordinated neural network function and information processing within the 40 hippocampus place cell system. We report in rats that PCP (5mg/kg i.p.) impairs a well-learned 41 hippocampus-dependent place avoidance behavior in rats that requires cognitive control, even 42 when PCP is injected directly into dorsal hippocampus. PCP increases 60-100 Hz medium 43 gamma oscillations in hippocampus CA1 and these increases correlate with the cognitive 44 impairment caused by systemic PCP administration. PCP discoordinates theta-modulated 45 medium and slow gamma oscillations in CA1 local field potentials (LFP) such that medium 46 gamma oscillations become more theta-organized than slow gamma oscillations. CA1 place cell 47 firing fields are preserved under PCP but the drug discoordinates the sub-second temporal 48 organization of discharge amongst place cells. This discoordination causes place cell ensemble 49 representations of a familiar space to cease resembling pre-PCP representations, despite 50 preserved place fields. These findings point to the cognitive impairments caused by PCP arising 51 from neural discoordination. PCP disrupts the timing of discharge with respect to the sub-second 52 timescales of theta and gamma oscillations in the LFP. Because these oscillations arise from 53 local inhibitory synaptic activity, these findings point to excitation-inhibition discoordination as 54 the root of PCP-induced cognitive impairment. 55 56 Kao et al 4 SIGNIFICANCE STATEMENT 57 58Hippocampal neural discharge is temporally coordinated on timescales of theta and gamma 59 oscillations in the local field potential, and the discharge of a subset of pyramidal neurons called 60 "place cells" is spatially organized such that discharge is restricted to locations called a cell's 61 "place field." Because this temporal coordination and spatial discharge organization is thought to 62 represent spatial knowledge, we used the psychotomimetic phencyclidine (PCP) to disrupt 63 cognitive behavior and assess the importance of neural coordination and place fields for spatial 64 cognition. PCP impaired the judicious use of spatial information and discoordinated hippocampal 65 discharge, without disrupting firing fields. These findings dissociate place fields from spatial 66 cognitive behavior and suggest that hippocampus discharge coordination is crucial to spatial 67 cognition. 69 70 Place cells are hippocampus principal cells that discharge in 'place fields' that map discharge to 71 locations, making place cell studies de facto investigations of what information the hippocampus 72 represents and how that information is represented (Friston

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Impairment of neural coordination in hippocampal neuronal ensembles after a psychotomimetic dose of dizocilpine

Cited by 8 publications

References 54 publications

Neural and neuronal discoordination in schizophrenia: From ensembles through networks to symptoms

Neural and neuronal discoordination in schizophrenia: From ensembles through networks to symptoms

Phencyclidine Disrupts Neural Coordination and Cognitive Control by Dysregulating Translation

Phencyclidine discoordinates hippocampal network activity but not place fields

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