Aberrant alpha and gamma oscillations ex vivo after single application of the NMDA receptor antagonist MK-801

Lemercier, Clément E.; Holman, Cheryl; Gerevich, Zoltán

doi:10.1016/j.schres.2017.01.017

Cited by 25 publications

(31 citation statements)

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“…To accomplish this, the effects of cariprazine were studied in hippocampal slices of rats that received a single dose of MK-801, a model of first-episode schizophrenia (Manahan-Vaughan et al, 2008;Wiescholleck & Manahan-Vaughan, 2013). In line with previous results (Lemercier et al, 2017), the hippocampal gamma oscillations induced by bath application of ACh (10 μM) and physostigmine (2 μM) had a significantly higher peak power after 90 min of induction compared to saline-treated animals (P < .001, Figure 5a,b,d) and a broader half bandwidth (MK-801:…”

Section: Cariprazine Stabilizes Hippocampal Gamma Oscillations In Msupporting

confidence: 91%

The novel antipsychotic cariprazine stabilizes gamma oscillations in rat hippocampal slices

Meier

Lemercier

Kulisch

et al. 2020

British J Pharmacology

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Background and Purpose Gamma oscillations are fast rhythmic fluctuations of neuronal network activity ranging from 30 to 90 Hz that establish a precise temporal background for cognitive processes such as perception, sensory processing, learning, and memory. Alterations of gamma oscillations have been observed in schizophrenia and are suggested to play crucial roles in the generation of positive, negative, and cognitive symptoms of the disease. Experimental Approach In this study, we investigated the effects of the novel antipsychotic cariprazine, a D3‐preferring dopamine D3/D2 receptor partial agonist, on cholinergically induced gamma oscillations in rat hippocampal slices from treatment‐naïve and MK‐801‐treated rats, a model of acute first‐episode schizophrenia. Key Results The D3 receptor‐preferring agonist pramipexole effectively decreased the power of gamma oscillations, while the D3 receptor antagonist SB‐277011 had no effect. In treatment‐naïve animals, cariprazine did not modulate strong gamma oscillations but slightly improved the periodicity of non‐saturated gamma activity. Cariprazine showed a clear partial agonistic profile at D3 receptors at the network level by potentiating the inhibitory effects when the D3 receptor tone was low and antagonizing the effects when the tone was high. In hippocampal slices of MK‐801‐treated rats, cariprazine allowed stabilization of the aberrant increase in gamma oscillation power and potentiated resynchronization of the oscillations. Conclusion and Implications Data from this study indicate that cariprazine stabilizes pathological hippocampal gamma oscillations, presumably by its partial agonistic profile. The results demonstrate in vitro gamma oscillations as predictive biomarkers to study the effects of antipsychotics preclinically at the network level.

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Section: Cariprazine Stabilizes Hippocampal Gamma Oscillations In Msupporting

confidence: 91%

The novel antipsychotic cariprazine stabilizes gamma oscillations in rat hippocampal slices

Meier

Lemercier

Kulisch

et al. 2020

British J Pharmacology

Self Cite

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“…Although regularity (periodicity) of neural oscillation has been measured using autocorrelation analysis (Red'ka and Mayorov, 2015), spectral entropy (Poza et al, 2012;Gomez-Pilar et al, 2016), sample entropy (Gomez and Hornero, 2010), auto-mutual information analysis (Gomez et al, 2007), Q factor (Lemercier et al, 2017), and lagged coherence (Fransen et al, 2015), no study has reported a perception-or attention-related increase in regularity in sensory areas (even an attention-related decrease in regularity was reported (Fransen et al, 2015)). We recorded neuromagnetic signals from the human brain at a high sampling rate of 4 kHz, directly depicting a distribution of IPIs.…”

Section: Discussionmentioning

confidence: 99%

Desynchronizing to be faster? Perceptual- and attentional-modulation of brain rhythms in sub-millisecond scale

Noguchi

Xia

Kakigi

2018

Preprint

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Neural oscillatory signals has been associated with many high-level functions (e.g. attention and working memory), because they reflect correlated behaviors of neural population that would facilitate the information transfer in the brain. On the other hand, a decreased power of oscillation (event-related desynchronization or ERD) has been associated with an irregular state in which many neurons behave in an uncorrelated manner. In contrast to this view, here we show that the human ERD is linked to the increased regularity of oscillatory signals. Using magnetoencephalography, we found that presenting a visual stimulus not only induced the ERD of alpha (8-13 Hz) and beta (13-30 Hz) rhythms in the contralateral visual cortex but also reduced the mean and variance of their inter-peak intervals (IPIs). This indicates that the suppressed alpha/beta rhythms became faster (reduced mean) and more regular (reduced variance) during visual stimulation. The same changes in IPIs, especially those of beta rhythm, were observed when subjects allocated their attention to a contralateral visual field. Those results revealed a new role of the ERD and further suggested that our brain regulates and accelerates a clock for neural computations by actively inducing the desynchronization in task-relevant regions.--3

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“…For example, Palenicek et al found increased EEG power particularly in the gamma band and coherence virtually across most rat cortical regions after systemic ketamine injection, which may further support the notion of the brain's inability to maintain distinct cortical functional states after the induction of schizophrenia‐like symptoms. Similarly, the application of a single MK‐801 dose to both HPC and PFC slices from rats causes a marked increase in LFP power in the gamma band . Interestingly, local application to either the PFC or the HPC results in similar changes in oscillatory activity as systemic injection .…”

Section: Discoordination In Large‐scale Networkmentioning

confidence: 95%

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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Aberrant alpha and gamma oscillations ex vivo after single application of the NMDA receptor antagonist MK-801

Cited by 25 publications

References 50 publications

The novel antipsychotic cariprazine stabilizes gamma oscillations in rat hippocampal slices

The novel antipsychotic cariprazine stabilizes gamma oscillations in rat hippocampal slices

Desynchronizing to be faster? Perceptual- and attentional-modulation of brain rhythms in sub-millisecond scale

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

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