A disinhibitory microcircuit initiates critical-period plasticity in the visual cortex

Abstract

Early sensory experience instructs the maturation of neural circuitry in the cortex1,2. This has been studied extensively in the primary visual cortex, in which loss of vision to one eye permanently degrades cortical responsiveness to that eye3,4, a phenomenon known as ocular dominance plasticity (ODP). Cortical inhibition mediates this process4,5,6, but the precise role of specific classes of inhibitory neurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in the primary visual cortex immediately drop by half when vision is restricted to one eye, but gradually return to normal over the following twenty-four hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates after monocular deprivation results from a rapid, although transient, reduction in the firing rates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turn can be attributed to a decrease in local excitatory circuit input onto PV interneurons. This reduction in PV-cell-evoked responses after monocular lid suture is restricted to the critical period for ODP and appears to be necessary for subsequent shifts in excitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic reduction of PV cell firing rates can extend the critical period for ODP. These findings define the microcircuit changes initiating competitive plasticity during critical periods of cortical development. Moreover, they show that the restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ODP.

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Figure 1: L2/3 pyramidal neuron responsiveness and local circuit organization is unchanged 1 day after MD.
Figure 2: L2/3 PV responsiveness to visual stimuli is reduced after 1-day MD.
Figure 3: L2/3 PV local circuit organization is altered after 1-day MD.
Figure 4: Reducing PV-specific inhibition restores ODP after the closure of the critical period.

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Acknowledgements

We thank S. Smith, W. Thompson, K. Miller and M. P. Stryker for comments on earlier versions of this manuscript, Y. Shi for help with software, Z. Nenadic for analytical suggestions, D. Ringach for help with GCaMP6 analysis and Z. J. Huang for useful discussions. This work was funded by grants from the US National Eye Institute (EY016052) to J.T.T., and the US National Institute of Neurological Disorders and Stroke (NS078434) and a NARSAD Young Investigator Grant to X.X.

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S.J.K. and E.T. performed the in vivo awake and anaesthetized recordings. S.J.K. performed the diazepam/OGB-1 experiments. E.T. performed the DREADD/GCamp6 experiments. N.D.O. and T.I. performed the glutamate uncaging experiments. X.X. oversaw the glutamate uncaging experiments. J.T.T. oversaw all aspects of the project. S.J.K., N.D.O., X.X. and J.T.T. wrote the manuscript and prepared the figures.

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Correspondence to Xiangmin Xu or Joshua T. Trachtenberg.

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Kuhlman, S., Olivas, N., Tring, E. et al. A disinhibitory microcircuit initiates critical-period plasticity in the visual cortex. Nature 501, 543–546 (2013). https://doi.org/10.1038/nature12485

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