Modulation of thalamo-cortical activity by the NMDA receptor antagonists ketamine and phencyclidine in the awake freely-moving rat

Amat-Foraster, Maria; Celada, Pau; Richter, Ulrike; Jensen, Anders A.; Plath, Niels; Artigas, Francesc; Herrik, Kjartan F.

doi:10.1016/j.neuropharm.2019.107745

Cited by 24 publications

(32 citation statements)

References 68 publications

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“…For instance, in general anaesthesia some drugs induce an enhancement of γ-activity in experimental mammalian EEG data, e.g. after the administration of ketamine [40,41] and propofol [42]. Since our model describe interacting neural networks, it is interesting to investigate whether it may explain this γ-enhancement.…”

Section: Effects Of Ketamine and Propofolmentioning

confidence: 99%

Poisson-distributed noise induces cortical γ-activity: explanation of γ-enhancement by anaesthetics ketamine and propofol

Wahl¹,

Hutt²

2021

J. Phys. Complex.

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Additive noise is known to aﬀect the stability of nonlinear systems. To understand better the role of additive noise in neural systems, we investigate the impact of additive noise on a random neural network of excitatory and inhibitory neurons. Here we hypothesize that the noise originates from the ascending reticular activating system (ARAS). Coherence resonance in the γ-frequency range emerges for intermediate noise levels while the network exhibits non-coherent activity at low and high noise levels. The analytical study of a corresponding mean-ﬁeld model system explains the resonance eﬀect by a noise-induced phase transition via a saddle-node bifurcation. An analytical study of the linear mean-ﬁeld systems response to additive noise reveals that the coherent state exhibits a quasi-cycle in the γ-frequency range whose spectral properties are tuned by the additive noise. To illustrate the importance of the work, we show that the quasi-cycle explains γ-enhancement under impact of the anaesthetics ketamine and propofol as a destabilizing eﬀect of the coherent state.

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Section: Effects Of Ketamine and Propofolmentioning

confidence: 99%

Poisson-distributed noise induces cortical γ-activity: explanation of γ-enhancement by anaesthetics ketamine and propofol

Wahl¹,

Hutt²

2021

J. Phys. Complex.

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“…Ketaminedependent faster stereotypic nasal respiration was associated with increased HFO power, but also slow basal respiration modulated HFO power in the presence of haloperidol. However, in the current study we did not examine the effect of low doses of ketamine, for example 3 mg/kg can produce weak increases in HFO without markedly altering locomotion 20 . Further studies are warranted to document the effect of other psychoactive compounds such as LSD or DOI which can increase HFO power without affecting locomotion 19,67 .…”

Section: Discussionmentioning

confidence: 92%

Nasal respiration is necessary for the emergence of ketamine-induced high frequency network oscillations and behavioral hyperactivity in freely moving rats

oacutebel¹,

Średniawa

Bernatowicz

et al. 2020

Preprint

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Changes in oscillatory activity are widely reported after subanesthetic ketamine, however their mechanisms of generation are unclear. Here, we tested the hypothesis that nasal respiration underlies the emergence of high-frequency oscillations (130-180 Hz, HFO) and behavioral activation after ketamine in freely moving rats. We found ketamine 20 mg/kg provoked “fast” theta sniffing in rodents which correlated with increased locomotor activity and HFO power in the OB. Bursts of ketamine-dependent HFO were coupled to “fast” theta frequency sniffing. Theta coupling of HFO bursts were also found in the prefrontal cortex and ventral striatum which, although of smaller amplitude, were in phase with OB activity. Haloperidol 1 mg/kg pretreatment prevented ketamine-dependent increases in fast sniffing and instead HFO coupling to slower basal respiration. Consistent with ketamine-dependent HFO being driven by nasal respiration, unilateral naris blockade led to an ipsilateral reduction in ketamine-dependent HFO power compared to the control side. Bilateral nares blockade reduced ketamine-induced hyperactivity and HFO power and frequency. In conclusion, nasal entrainment of ketamine-dependent HFO across cortical and subcortical regions at theta frequencies represents a mechanism of orchestrated neural activity across distinct brain regions. The dense divergent connectivity of the olfactory system serves to broadcast this HFO to limbic areas.

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“…The present study was also aimed at investigating the neurochemical effects of acute ketamine treatment in mPFC, since this is a converging anatomical substrate for the psychotomimetic and antidepressant effects of ketamine and a relevant area in the pathophysiology of schizophrenia and depression 66,67 . NMDA-R antagonists cause net disruptions of population activity and enhance gamma and high-frequency oscillations in mPFC 26 . On the other hand, Glu and 5-HT neurotransmission in infralimbic cortex (IL, ventral subdivision of the mPFC) seems crucial for antidepressant-like responses in rodents 68,69 .…”

Section: Discussionmentioning

confidence: 99%

“…Ketamine, despite inhibiting RtN neurons, evokes a further inhibition of thalamo-cortical activity in anesthetized rats 21 . However, both agents show a similar action in freely moving rats, enhancing the activity of thalamic and cortical neurons, including that of GABAergic interneurons 26 , which suggests a mechanism of action different from that of MK-801 19 , at least in cortical networks.…”

Section: Introductionmentioning

confidence: 91%

Involvement of NMDA receptors containing the GluN2C subunit in the psychotomimetic and antidepressant-like effects of ketamine

et al. 2020

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Acute ketamine administration evokes rapid and sustained antidepressant effects in treatment-resistant patients. However, ketamine also produces transient perceptual disturbances similarly to those evoked by other non-competitive NMDA-R antagonists like phencyclidine (PCP). Although the brain networks involved in both ketamine actions are not fully understood, PCP and ketamine activate thalamo-cortical networks after NMDA-R blockade in GABAergic neurons of the reticular thalamic nucleus (RtN). Given the involvement of thalamo-cortical networks in processing sensory information, these networks may underlie psychotomimetic action. Since the GluN2C subunit is densely expressed in the thalamus, including the RtN, we examined the dependence of psychotomimetic and antidepressant-like actions of ketamine on the presence of GluN2C subunits, using wild-type and GluN2C knockout (GluN2CKO) mice. Likewise, since few studies have investigated ketamine’s effects in females, we used mice of both sexes. GluN2C deletion dramatically reduced stereotyped (circling) behavior induced by ketamine in male and female mice, while the antidepressant-like effect was fully preserved in both genotypes and sexes. Despite ketamine appeared to induce similar effects in both sexes, some neurobiological differences were observed between male and female mice regarding c-fos expression in thalamic nuclei and cerebellum, and glutamate surge in prefrontal cortex. In conclusion, the GluN2C subunit may discriminate between antidepressant-like and psychotomimetic actions of ketamine. Further, the abundant presence of GluN2C subunits in the cerebellum and the improved motor coordination of GluN2CKO mice after ketamine treatment suggest the involvement of cerebellar NMDA-Rs in some behavioral actions of ketamine.

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Modulation of thalamo-cortical activity by the NMDA receptor antagonists ketamine and phencyclidine in the awake freely-moving rat

Cited by 24 publications

References 68 publications

Poisson-distributed noise induces cortical γ-activity: explanation of γ-enhancement by anaesthetics ketamine and propofol

Poisson-distributed noise induces cortical γ-activity: explanation of γ-enhancement by anaesthetics ketamine and propofol

Nasal respiration is necessary for the emergence of ketamine-induced high frequency network oscillations and behavioral hyperactivity in freely moving rats

Involvement of NMDA receptors containing the GluN2C subunit in the psychotomimetic and antidepressant-like effects of ketamine

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