Subanesthetic ketamine reactivates adult cortical plasticity to restore vision from amblyopia
Steven F. Grieco, Xin Qiao, Xiaoting Zheng, Yongjun Liu, Lujia Chen, Hai Zhang, Jeffrey Gavornik, Cary Lai, Sunil P Gandhi, Todd C. Holmes, Xiangmin Xu
bioRxiv Preprint Server March 16, 2020 preprint DOI: 10.1101/2020.03.16.994475 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Adult mice |
| Intervention | Ketamine |
| Dose | single-dose |
| Topics | Neuroplasticity Esketamine Ketamine |
| Keywords | Brain flexibility Brain malleability Brain adaptability Vision restoration Sight recovery Visual recovery Vision repair Eyesight restoration Amblyopia treatment Visual acuity improvement Neurological treatment Brain therapy Neurotherapy Brain disorder treatment Neurological intervention Brain-based therapy |
| Citations | 14 |
| Key findings | Ketamine reactivates adult visual cortical plasticity and promotes functional recovery from amblyopia through rapid and sustained cortical disinhibition mediated by downregulation of NRG1 signaling in parvalbumin-expressing inhibitory neurons. |
Abstract
Subanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine’s effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically induces down-regulation of neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons in mouse visual cortex. NRG1 downregulation in PV neurons co-tracks both the fast onset and sustained decreases in synaptic inhibition to excitatory neurons, along with reduced synaptic excitation to PV neurons in vitro and in vivo following a single ketamine treatment. These effects are blocked by exogenous NRG1 as well as PV targeted receptor knockout. Thus ketamine reactivation of adult visual cortical plasticity is mediated through rapid and sustained cortical disinhibition via downregulation of PV-specific NRG1 signaling. Our findings reveal the neural plasticity-based mechanism for ketamine-mediated functional recovery from adult amblyopia.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 3
- Ketamine: Neuroprotective or Neurotoxic? Frontiers in Neuroscience September 10, 2021
- Critical Period Plasticity as a Framework for Psychedelic-Assisted Psychotherapy Frontiers in Neuroscience September 20, 2021
- Neuregulin signaling mediates the acute and sustained antidepressant effects of subanesthetic ketamine Translational Psychiatry February 24, 2021
Cites 12
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase Science December 6, 2007
and 7 more in the library