Subanesthetic ketamine reactivates adult cortical plasticity to restore vision from amblyopia

Grieco, Steven F.; Qiao, Xin; Zheng, Xiaoting; Liu, Yongjun; Chen, Lujia; Zhang, Hai; Gavornik, Jeffrey P.; Lai, Cary; Gandhi, Sunil; Holmes, Todd C.; Xu, Xiangmin

doi:10.1101/2020.03.16.994475

Cited by 3 publications

(1 citation statement)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The acute injection of KET can increase synaptic and structural plasticity in brain regions such as Hp and prefrontal cortex (PFC) (Aleksandrova et al, 2010;Grieco et al, 2020;Kang et al, 2020), an effect apparently mediated by the mTORC1 signaling pathway (Pazini et al, 2020). Accordingly, acute injection of KET induces a transient increase in phospho-mTOR and its targets, phospho-p70S6 kinase and phospho-4E-BP1, in both PFC and Hp of rodents (Zhang et al, 2017;Johnston et al, 2020;Pazini et al, 2020), whereas mTORC1 inhibition can slow down the behavioral and molecular events that may give to KET its antidepressant effect (Abdallah et al, 2020).…”

Section: Pharmacological Properties Of Ketmentioning

confidence: 99%

Ketamine as a pharmacological tool for the preclinical study of memory deficit in schizophrenia

Santiago

Roldán

Picazo

2022

Behavioural Pharmacology

View full text Add to dashboard Cite

Schizophrenia is a serious neuropsychiatric disorder characterized by the presence of positive symptoms (hallucinations, delusions, and disorganization of thought and language), negative symptoms (abulia, alogia, and affective flattening), and cognitive impairment (attention deficit, impaired declarative memory, and deficits in social cognition). Dopaminergic hyperactivity seems to explain the positive symptoms, but it does not completely clarify the appearance of negative and cognitive clinical manifestations. Preclinical data have demonstrated that acute and subchronic treatment with NMDA receptor antagonists such as ketamine (KET) represents a useful model that resembles the schizophrenia symptomatology, including cognitive impairment. This latter has been explained as a hypofunction of NMDA receptors located on the GABA parvalbumin-positive interneurons (near to the cortical pyramidal cells), thus generating an imbalance between the inhibitory and excitatory activity in the corticomesolimbic circuits. The use of behavioral models to explore alterations in different domains of memory is vital to learn more about the neurobiological changes that underlie schizophrenia. Thus, to better understand the neurophysiological mechanisms involved in cognitive impairment related to schizophrenia, the purpose of this review is to analyze the most recent findings regarding the effect of KET administration on these processes.

show abstract

Section: Pharmacological Properties Of Ketmentioning

confidence: 99%

Ketamine as a pharmacological tool for the preclinical study of memory deficit in schizophrenia

Santiago

Roldán

Picazo

2022

Behavioural Pharmacology

View full text Add to dashboard Cite

show abstract

Ketamine promotes adaption-induced orientation plasticity and vigorous network changes

Ouelhazi¹,

Lussiez²,

Molotchnikoff³

2022

Brain Research

View full text Add to dashboard Cite

Spectral Signatures of L-DOPA-Induced Dyskinesia Depend on L-DOPA Dose and are Suppressed by Ketamine

Bartlett

Sherman

et al. 2020

Preprint

View full text Add to dashboard Cite

L-DOPA-induced dyskinesias (LID) are debilitating motor symptoms of dopamine-replacement therapy for Parkinson′s disease (PD) that emerge after years of L-DOPA treatment. While there is an abundance of research into the cellular and synaptic origins of LID, less is known about how LID impacts systems-level circuits and neural synchrony, how synchrony is affected by the dose and duration of L-DOPA exposure, or how potential novel treatments for LID, such as sub- anesthetic ketamine, alter this activity. Sub-anesthetic ketamine treatments have recently been shown to reduce LID, and ketamine is known to affect neural synchrony. To investigate these questions, we measured locomotor and local-field potential (LFP) activity from the motor cortex (M1) and the striatum of preclinical rodent models of PD and LID. In the first experiment, we investigated the effect of the LID priming procedures and L-DOPA dose on neural signatures of LID. Two common priming procedures were compared: a high-dose procedure that exposed unilateral 6-hydroxydopamine-lesioned rats to 12 mg/kg L-DOPA for 7 days, and a low-dose procedure that exposed rats to 7 mg/kg L-DOPA for 21 days. Consistent with reports from other groups, high-dose priming triggered LID and 80-Hz oscillations; however, these 80-Hz oscillations were not observed under the low-dose procedure despite clear evidence of LID, indicating that 80- Hz oscillations are not an exclusive signature of LID. Instead, the low-dose procedure resulted in the weeks-long gradual emergence of non-oscillatory broadband gamma activity (> 30 Hz) in the striatum and theta-to-high-gamma cross-frequency coupling (CFC) in M1. In a second set of experiments, we investigated how ketamine exposure affects spectral signatures of low-dose L- DOPA priming. During each neural recording session, ketamine was delivered through 5 injections (20 mg/kg, i.p.) administered every 2 hours. We found that ketamine exposure suppressed striatal broadband gamma associated with LID, but enhanced M1 broadband activity. We also found that M1 theta-to-high-gamma CFC associated with the LID on-state was suppressed by ketamine. These results suggest that ketamine′s therapeutic effects are region specific. Our findings also have clinical implications as we are the first to report novel oscillatory signatures associated with the common low-dose LID priming procedure that more closely models dopamine replacement therapy in individuals with PD, and as we identify neural correlates of the anti-dyskinetic activity of sub-anesthetic ketamine treatment.

show abstract

Subanesthetic ketamine reactivates adult cortical plasticity to restore vision from amblyopia

Cited by 3 publications

References 61 publications

Ketamine as a pharmacological tool for the preclinical study of memory deficit in schizophrenia

Ketamine as a pharmacological tool for the preclinical study of memory deficit in schizophrenia

Ketamine promotes adaption-induced orientation plasticity and vigorous network changes

Spectral Signatures of L-DOPA-Induced Dyskinesia Depend on L-DOPA Dose and are Suppressed by Ketamine

Contact Info

Product

Resources

About