Eye opening differentially modulates inhibitory synaptic transmission in the developing visual cortex
- Fudan University, China
Abstract
Eye opening, a natural and timed event during animal development, influences cortical circuit assembly and maturation; yet, little is known about its precise effect on inhibitory synaptic connections. Here we show that coinciding with eye opening, the strength of unitary inhibitory postsynaptic currents (uIPSCs) from somatostatin-expressing interneurons (Sst-INs) to nearby excitatory neurons, but not interneurons, sharply decreases in layer 2/3 of the mouse visual cortex. In contrast, the strength of uIPSCs from fast-spiking interneurons (FS-INs) to excitatory neurons significantly increases during eye opening. More importantly, these developmental changes can be prevented by dark rearing or binocular lid suture, and reproduced by the artificial opening of sutured lids. Mechanistically, this differential maturation of synaptic transmission is accompanied by a significant change in the postsynaptic quantal size. Together, our study reveals a differential regulation in GABAergic circuits in the cortex driven by eye opening may be crucial for cortical maturation and function.
Article and author information
Author details
Funding
National Key Research and Development Program of China (2016YFA0100802)
- Yinghui Fu
Ministry of Education of the People's Republic of China (20130071110065)
- Yong-Chun Yu
Science and Technology Commission of Shanghai Municipality (No.15JC1400102)
- Yong-Chun Yu
Science and Technology Commission of Shanghai Municipality (15XD1500700)
- Yong-Chun Yu
National Natural Science Foundation of China (31200816)
- Yinghui Fu
National Natural Science Foundation of China (31271157)
- Yong-Chun Yu
National Natural Science Foundation of China (31471036)
- Yong-Chun Yu
National Natural Science Foundation of China (31629004)
- Yong-Chun Yu
National Natural Science Foundation of China (31421091)
- Yong-Chun Yu
National Natural Science Foundation of China (91332110)
- Yong-Chun Yu
Ministry of Science and Technology of the People's Republic of China (2014CB942800)
- Yong-Chun Yu
Ministry of Science and Technology of the People's Republic of China (2012CB966303)
- Yong-Chun Yu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Marlene Bartos, University of Freiburg, Germany
Ethics
Animal experimentation: All surgical and experimental procedures were in accordance with the protocols approved by the Committee on the Ethics of Animal Experiments of Fudan University Shanghai Medical College (permit number: 20110307-049). All surgery was performed under isoflurane anesthesia and ethanol disinfection to minimize suffering.
Version history
- Received: September 27, 2017
- Accepted: December 8, 2017
- Accepted Manuscript published: December 11, 2017 (version 1)
- Version of Record published: December 28, 2017 (version 2)
Copyright
© 2017, Guan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Eye opening differentially modulates inhibitory synaptic transmission in the developing visual cortex
eLife 6:e32337.
https://doi.org/10.7554/eLife.32337
Further reading
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- Neuroscience
The presence of global synchronization of vasomotion induced by oscillating visual stimuli was identified in the mouse brain. Endogenous autofluorescence was used and the vessel ‘shadow’ was quantified to evaluate the magnitude of the frequency-locked vasomotion. This method allows vasomotion to be easily quantified in non-transgenic wild-type mice using either the wide-field macro-zoom microscopy or the deep-brain fiber photometry methods. Vertical stripes horizontally oscillating at a low temporal frequency (0.25 Hz) were presented to the awake mouse, and oscillatory vasomotion locked to the temporal frequency of the visual stimulation was induced not only in the primary visual cortex but across a wide surface area of the cortex and the cerebellum. The visually induced vasomotion adapted to a wide range of stimulation parameters. Repeated trials of the visual stimulus presentations resulted in the plastic entrainment of vasomotion. Horizontally oscillating visual stimulus is known to induce horizontal optokinetic response (HOKR). The amplitude of the eye movement is known to increase with repeated training sessions, and the flocculus region of the cerebellum is known to be essential for this learning to occur. Here, we show a strong correlation between the average HOKR performance gain and the vasomotion entrainment magnitude in the cerebellar flocculus. Therefore, the plasticity of vasomotion and neuronal circuits appeared to occur in parallel. Efficient energy delivery by the entrained vasomotion may contribute to meeting the energy demand for increased coordinated neuronal activity and the subsequent neuronal circuit reorganization.
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- Medicine
- Neuroscience
Background:
Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine’s molecular mechanisms connect to its neural and behavioral effects.
Methods:
We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets.
Results:
We found that: (i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; (ii) ketamine’s data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level.
Conclusions:
These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry.
Funding:
This study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1–190420) (FXV, KHP); Swiss Neuromatrix Foundation (Grant No. 2016–0111) (FXV, KHP); Swiss National Science Foundation under the framework of Neuron Cofund (Grant No. 01EW1908) (KHP); Usona Institute (2015 – 2056) (FXV).
Clinical trial number:
