Subanesthetic ketamine reactivates adult cortical plasticity to restore vision from amblyopia
- Resource Type
- Authors
- Yong-Jun Liu; Hai Zhang; Lujia Chen; Todd C. Holmes; Xiangmin Xu; Jeffrey P. Gavornik; Cary Lai; Sunil P. Gandhi; Steven F. Grieco; Xin Qiao; Xiaoting Zheng
- Source
- Subject
- 0303 health sciences
Biology
Inhibitory postsynaptic potential
03 medical and health sciences
0302 clinical medicine
Visual cortex
medicine.anatomical_structure
Downregulation and upregulation
Disinhibition
mental disorders
Neuroplasticity
medicine
Excitatory postsynaptic potential
Antidepressant
Ketamine
medicine.symptom
Neuroscience
030217 neurology & neurosurgery
030304 developmental biology
medicine.drug
- Language
SummarySubanesthetic 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 neuronsin vitroandin vivofollowing 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.Highlights○ Disinhibition of excitatory cells by ketamine occurs in a fast and sustained manner○ Ketamine evokes NRG1 downregulation and excitatory input loss to PV cells○ Ketamine induced plasticity is blocked by exogenous NRG1 or its receptor knockout○ PV inhibitory cells are the initial functional locus underlying ketamine’s effects