Circuitry Underlying Experience-Dependent Plasticity in the Mouse Visual System
Authors: Bryan M. Hooks, Chinfei Chen
Journal: Neuron (2020)

Since the discovery of ocular dominance plasticity, neuroscientists have understood that changes in visual experience during a discrete developmental time, the critical period, trigger robust changes in the visual cortex. State-of-the-art tools used to probe connectivity with cell-type-specific resolution have expanded the understanding of circuit changes underlying experience-dependent plasticity. Here, we review the visual circuitry of the mouse, describing projections from retina to thalamus, between thalamus and cortex, and within cortex. We discuss how visual circuit development leads to precise connectivity and identify synaptic loci, which can be altered by activity or experience. Plasticity extends to visual features beyond ocular dominance, involving subcortical and cortical regions, and connections between cortical inhibitory interneurons. Experience-dependent plasticity contributes to the alignment of networks spanning retina to thalamus to cortex. Disruption of this plasticity may underlie aberrant sensory processing in some neurodevelopmental disorders. Since the discovery of ocular dominance plasticity, neuroscientists have understood that changes in visual experience during a discrete developmental time, the critical period, trigger robust changes in the visual cortex. State-of-the-art tools used to probe connectivity with cell-type-specific resolution have expanded the understanding of circuit changes underlying experience-dependent plasticity. Here, we review the visual circuitry of the mouse, describing projections from retina to thalamus, between thalamus and cortex, and within cortex. We discuss how visual circuit development leads to precise connectivity and identify synaptic loci, which can be altered by activity or experience. Plasticity extends to visual features beyond ocular dominance, involving subcortical and cortical regions, and connections between cortical inhibitory interneurons. Experience-dependent plasticity contributes to the alignment of networks spanning retina to thalamus to cortex. Disruption of this plasticity may underlie aberrant sensory processing in some neurodevelopmental disorders. Vision is so inseparable from our conception of the world that "seeing is believing." Sight is crucial to recognize friends, find savory food, and plan movement. While some aspects of the visual system form in utero, visual circuits have significant spontaneous activity- and experience-dependent reorganization early in life. Developmental refinement is robust to perturbations and small errors, imparting uniqueness based on experience without an exhaustive molecular code specifying each connection. Developmental circuit changes occur at specific time points. The best-known changes occur during sensitive periods (SPs) and critical periods (CPs). SPs are developmental time windows when neuronal circuits exhibit experience-dependent modification. Such changes are easily evoked and of greater magnitude during the SP, but can be evoked to a smaller extent at other ages. CPs are a subset of SPs, distinguished by a strict temporal onset and closure and the fact that experience during the period is required for subsequent normal connectivity and function (Voss, 2013Voss P. Sensitive and critical periods in visual sensory deprivation.Front. Psychol. 2013; 4: 664Crossref PubMed Scopus (25) Google Scholar). This change is not reversible except during the CP. The early developmental CP was described by Hubel and Wiesel. In binocular visual cortex, responsiveness to visual input from a deprived eye is attenuated by weeks of monocular deprivation (MD). This change in ocular dominance (OD), called ocular dominance plasticity (ODP), only occurs for deprivation early in development. Moreover, the circuit changes include a reduction in acuity in the deprived eye, called amblyopia. While changes in ODP and acuity can be reversed during the CP, recovery is not possible once the CP closes. Growing evidence suggests that ODP is not entirely extinguished by the CP closure. Substantial adult plasticity outside of the CP can be activated, often with stimulus paradigms distinct from those effective during the CP (Espinosa and Stryker, 2012Espinosa J.S. Stryker M.P. Development and plasticity of the primary visual cortex.Neuron. 2012; 75: 230-249Abstract Full Text Full Text PDF PubMed Scopus (294) Google Scholar, Fong et al., 2016Fong M.F. Mitchell D.E. Duffy K.R. Bear M.F. Rapid recovery from the effects of early monocular deprivation is enabled by temporary inactivation of the retinas.Proc Natl Acad Sci U S A. 2016; 113: 14139-14144Crossref PubMed Scopus (14) Google Scholar, Hensch and Quinlan, 2018Hensch T.K. Quinlan E.M. Critical periods in amblyopia.Vis. Neurosci. 2018; 35: E014PubMed Google Scholar, Sato and Stryker, 2008Sato M. Stryker M.P. Distinctive features of adult ocular dominance plasticity.J. Neurosci. 2008; 28: 10278-10286Crossref PubMed Scopus (153) Google Scholar). Thus, ODP is perhaps more accurately defined as occurring during an SP. This ambiguity highlights the difficulty in distinguishing between CP and SP, especially as more sensitive tools to monitor function are developed. Different synaptic loci along the visual pathway can vary in their sensitivity to experience (Kang et al., 2013Kang E. Durand S. LeBlanc J.J. Hensch T.K. Chen C. Fagiolini M. Visual acuity development and plasticity in the absence of sensory experience.J. Neurosci. 2013; 33: 17789-17796Crossref PubMed Scopus (42) Google Scholar), and a change in one synapse that may exhibit reversible plasticity can have an enduring effect on overall function because of its influence on downstream synapses that change irreversibly. Homeostatic responses can also be activated to compensate for changes in one synapse, but not another synapse (Whitt et al., 2014Whitt J.L. Petrus E. Lee H.K. Experience-dependent homeostatic synaptic plasticity in neocortex.Neuropharmacology. 2014; 78: 45-54Crossref PubMed Scopus (39) Google Scholar). In the end, the visual circuit is indelibly altered by experience. Therefore, for the purpose of this review, we define CPs as a window of time during which there is a distinct onset of plasticity in response to experience that is followed by a clear diminishing responsiveness to the same stimuli. Since Hubel and Wiesel, ODP has served as a robust model for studying CP plasticity. Changes in ODP following MD can be measured by comparing the neuronal response (by single unit recordings, visual evoked responses [VEPs], or in vivo imaging) to visual stimulation of each eye. These straightforward measurements have made ODP a canonical experimental system. More recently, tools enabling the measurement of other visual features such as orientation preference suggest that many visual features show plasticity, occasionally with different rules. This implies that the plasticity of traditionally monocular circuitry, such as thalamic relay cells, may show developmentally regulated plasticity in features unrelated to OD shifts. Considerable effort has been devoted to understanding the underlying circuit and molecular basis of CP plasticity (Fagiolini et al., 2004Fagiolini M. Fritschy J.M. Löw K. Möhler H. Rudolph U. Hensch T.K. Specific GABAA circuits for visual cortical plasticity.Science. 2004; 303: 1681-1683Crossref PubMed Scopus (332) Google Scholar). The means to label, monitor, and manipulate these circuit components independently is crucial to understand the basic visual circuit and to identify the loci where plasticity results in synaptic changes. Thus, the mouse has been a powerful experimental model. Despite a smaller binocular zone and lower visual acuity (Fagiolini et al., 1994Fagiolini M. Pizzorusso T. Berardi N. Domenici L. Maffei L. Functional postnatal development of the rat primary visual cortex and the role of visual experience: dark rearing and monocular deprivation.Vision Res. 1994; 34: 709-720Crossref PubMed Scopus (491) Google Scholar), mice exhibit an MD response similar to that of primates and cats. This ODP has a clearly defined CP between postnatal day 19 (P19) and P32 (Gordon and Stryker, 1996Gordon J.A. Stryker M.P. Experience-dependent plasticity of binocular responses in the primary visual cortex of the mouse.J. Neurosci. 1996; 16: 3274-3286Crossref PubMed Google Scholar). Mice offer the possibility of genetic access to defined neuron populations during ODP, including subsets of excitatory (Gerfen et al., 2013Gerfen C.R. Paletzki R. Heintz N. GENSAT BAC cre-recombinase driver lines to study the functional organization of cerebral cortical and basal ganglia circuits.Neuron. 2013; 80: 1368-1383Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar) and inhibitory neurons (Taniguchi et al., 2011Taniguchi H. He M. Wu P. Kim S. Paik R. Sugino K. Kvitsiani D. Fu Y. Lu J. Lin Y. et al.A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex.Neuron. 2011; 71: 995-1013Abstract Full Text Full Text PDF PubMed Scopus (822) Google Scholar). Such genetic approaches allow targeted recording, optical manipulation (Madisen et al., 2012Madisen L. Mao T. Koch H. Zhuo J.M. Berenyi A. Fujisawa S. Hsu Y.W. Garcia 3rd, A.J. Gu X. Zanella S. et al.A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing.Nat. Neurosci. 2012; 15: 793-802Crossref PubMed Scopus (616) Google Scholar), and calcium indicators to monitor activity (Chen et al., 2013Chen T.W. Wardill T.J. Sun Y. Pulver S.R. Renninger S.L. Baohan A. Schreiter E.R. Kerr R.A. Orger M.B. Jayaraman V. et al.Ultrasensitive fluorescent proteins for imaging neuronal activity.Nature. 2013; 499: 295-300Crossref PubMed Scopus (2349) Google Scholar). We review advances in circuit changes underlying experience-dependent plasticity, focusing on the mouse visual system. CPs across other species, adult plasticity, and molecular mechanisms are reviewed elsewhere (Hensch and Quinlan, 2018Hensch T.K. Quinlan E.M. Critical periods in amblyopia.Vis. Neurosci. 2018; 35: E014PubMed Google Scholar, Kiorpes, 2015Kiorpes L. Visual development in primates: neural mechanisms and critical periods.Dev. Neurobiol. 2015; 75: 1080-1090Crossref PubMed Google Scholar). We refer to work in other sensory cortical areas, extrapolating to the visual cortex. Studies have revealed that CPs apply to more than simply OD. With a variety of manipulations of visual experience and quantifying changes in receptive field (RF) properties, including orientation, luminance, and spatial and temporal frequency tuning, findings suggest the rules for plasticity in these features may differ from those for ODP. These studies also demonstrate that subcortical areas, including the thalamus, show experience-dependent changes. To understand where and how visual system plasticity is instantiated, a detailed system map is needed, including long-range connections between major brain structures (Figures 1 and 2) and the connections of specific cell types (Figures 3 and 4). This is especially true in the neocortex, which contains many distinct cell types, organized in layers, with multiple cell types per layer. A near-complete census of mouse cell types (Sugino et al., 2019Sugino K. Clark E. Schulmann A. Shima Y. Wang L. Hunt D.L. Hooks B.M. Tränkner D. Chandrashekar J. Picard S. et al.Mapping the transcriptional diversity of genetically and anatomically defined cell populations in the mouse brain.eLife. 2019; 8: e38619Crossref PubMed Scopus (3) Google Scholar, Tasic et al., 2018Tasic B. Yao Z. Graybuck L.T. Smith K.A. Nguyen T.N. Bertagnolli D. Goldy J. Garren E. Economo M.N. Viswanathan S. et al.Shared and distinct transcriptomic cell types across neocortical areas.Nature. 2018; 563: 72-78Crossref PubMed Scopus (167) Google Scholar) promises to identify the full range of molecular subtypes. This provides a parts list for the local circuit. Given a map of visual cortical circuitry, can we identify the connections that are profoundly altered during plasticity? Our aim is to place the temporal order of circuit changes in context, assessing whether there is a hierarchy such that plasticity occurs earlier or in a different way for circuit nodes in thalamus and thalamocortical (TC) afferents compared to the intracortical circuitry of L4 and L2/3.Figure 2Thalamocortical (TC) OrganizationShow full caption(A) Visual thalamus includes dorsal and ventral subdivisions (dLGN and vLGN, blue and purple). Core and shell areas of dLGN receive inputs from distinct RGC cell types. Higher-order visual thalamus includes LP (red).(B) Thalamic axons in V1 arborize in distinct cortical laminae.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Inhibitory and Excitatory Local Connectivity in CortexShow full caption(A) Inhibitory interneurons vary in their laminar distribution across the cortex. 5-HT3AR+ neurons are concentrated in L1 and L2/3, including the VIP+ interneurons. PV+ and SST+ interneurons are present across all of the layers, except L1 (after Lee et al., 2010Lee S. Hjerling-Leffler J. Zagha E. Fishell G. Rudy B. The largest group of superficial neocortical GABAergic interneurons expresses ionotropic serotonin receptors.J. Neurosci. 2010; 30: 16796-16808Crossref PubMed Scopus (323) Google Scholar, Xu et al., 2010Xu X. Roby K.D. Callaway E.M. Immunochemical characterization of inhibitory mouse cortical neurons: three chemically distinct classes of inhibitory cells.J. Comp. Neurol. 2010; 518: 389-404Crossref PubMed Scopus (256) Google Scholar). Subtypes are highlighted in the table at right.(B) In L2/3, bipolar VIP+ interneurons disinhibit the cortex by specifically inhibiting SST+ neurons. SST+ cells tonically inhibit PV+ neurons and pyramidal (Pyr) neuron apical dendrites. Tonic inhibition is released when VIP+ neurons become active (Pfeffer et al., 2013Pfeffer C.K. Xue M. He M. Huang Z.J. Scanziani M. Inhibition of inhibition in visual cortex: the logic of connections between molecularly distinct interneurons.Nat. Neurosci. 2013; 16: 1068-1076Crossref PubMed Scopus (527) Google Scholar). Input to VIP neurons (black and magenta arrows) may vary across cortical areas. Local inhibitory circuits differ in L4, where SST+ interneurons also inhibit PV+ cells, but VIP+ neurons are less abundant.(C and D) Major excitatory connections of the granular and supragranular visual cortex. The local excitatory circuit includes connections from excitatory cells in a given layer to those in nearby layers (Xu et al., 2016Xu X. Olivas N.D. Ikrar T. Peng T. Holmes T.C. Nie Q. Shi Y. Primary visual cortex shows laminar-specific and balanced circuit organization of excitatory and inhibitory synaptic connectivity.J. Physiol. 2016; 594: 1891-1910Crossref PubMed Google Scholar). Ascending (left) and descending projections (right), with thicknesses proportional to excitatory connection strength. Laminae targeted by thalamic input shown in blue and red. Strength is shown in the illustration (C) and as a connectivity matrix (D), with pre- and postsynaptic layers labeled.(E) Local excitatory connectivity in L2/3 and L4.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 4Developmental Changes in Cortical Connectivity Near the Critical Period (CP)Show full caption(A) For granular and supragranular layers, developmental changes in the connectivity of local circuits are illustrated. Excitatory neurons are illustrated in black. PV+ (blue), SST+ (burgundy), and VIP+ (green) inputs are color coded, along with neuromodulatory inputs such as acetylcholine (purple). Excitatory TC inputs are shown in black. Developmental age and time are annotated at the bottom. L4 changes in interneuron connectivity precede L2/3 changes (Jiang et al., 2010Jiang B. Sohya K. Sarihi A. Yanagawa Y. Tsumoto T. Laminar-specific maturation of GABAergic transmission and susceptibility to visual deprivation are related to endocannabinoid sensitivity in mouse visual cortex.J. Neurosci. 2010; 30: 14261-14272Crossref PubMed Scopus (33) Google Scholar), with PV maturation in L2/3 correlated in time to CP onset and closure (Fagiolini et al., 2004Fagiolini M. Fritschy J.M. Löw K. Möhler H. Rudolph U. Hensch T.K. Specific GABAA circuits for visual cortical plasticity.Science. 2004; 303: 1681-1683Crossref PubMed Scopus (332) Google Scholar). L2/3 connectivity matures during this period (Cossell et al., 2015Cossell L. Iacaruso M.F. Muir D.R. Houlton R. Sader E.N. Ko H. Hofer S.B. Mrsic-Flogel T.D. Functional organization of excitatory synaptic strength in primary visual cortex.Nature. 2015; 518: 399-403Crossref PubMed Scopus (191) Google Scholar, Ko et al., 2013Ko H. Cossell L. Baragli C. Antolik J. Clopath C. Hofer S.B. Mrsic-Flogel T.D. The emergence of functional microcircuits in visual cortex.Nature. 2013; 496: 96-100Crossref PubMed Scopus (198) Google Scholar). SST+ connectivity to PV+ neurons, initially strong, grows weaker during this time and loses sensitivity to cholinergic modulation (Yaeger et al., 2019Yaeger C.E. Ringach D.L. Trachtenberg J.T. Neuromodulatory control of localized dendritic spiking in critical period cortex.Nature. 2019; 567: 100-104Crossref PubMed Scopus (14) Google Scholar).(B) Mature connectivity is summarized.View Large Image Figure ViewerDownload Hi-res image Download (PPT) (A) Visual thalamus includes dorsal and ventral subdivisions (dLGN and vLGN, blue and purple). Core and shell areas of dLGN receive inputs from distinct RGC cell types. Higher-order visual thalamus includes LP (red). (B) Thalamic axons in V1 arborize in distinct cortical laminae. (A) Inhibitory interneurons vary in their laminar distribution across the cortex. 5-HT3AR+ neurons are concentrated in L1 and L2/3, including the VIP+ interneurons. PV+ and SST+ interneurons are present across all of the layers, except L1 (after Lee et al., 2010Lee S. Hjerling-Leffler J. Zagha E. Fishell G. Rudy B. The largest group of superficial neocortical GABAergic interneurons expresses ionotropic serotonin receptors.J. Neurosci. 2010; 30: 16796-16808Crossref PubMed Scopus (323) Google Scholar, Xu et al., 2010Xu X. Roby K.D. Callaway E.M. Immunochemical characterization of inhibitory mouse cortical neurons: three chemically distinct classes of inhibitory cells.J. Comp. Neurol. 2010; 518: 389-404Crossref PubMed Scopus (256) Google Scholar). Subtypes are highlighted in the table at right. (B) In L2/3, bipolar VIP+ interneurons disinhibit the cortex by specifically inhibiting SST+ neurons. SST+ cells tonically inhibit PV+ neurons and pyramidal (Pyr) neuron apical dendrites. Tonic inhibition is released when VIP+ neurons become active (Pfeffer et al., 2013Pfeffer C.K. Xue M. He M. Huang Z.J. Scanziani M. Inhibition of inhibition in visual cortex: the logic of connections between molecularly distinct interneurons.Nat. Neurosci. 2013; 16: 1068-1076Crossref PubMed Scopus (527) Google Scholar). Input to VIP neurons (black and magenta arrows) may vary across cortical areas. Local inhibitory circuits differ in L4, where SST+ interneurons also inhibit PV+ cells, but VIP+ neurons are less abundant. (C and D) Major excitatory connections of the granular and supragranular visual cortex. The local excitatory circuit includes connections from excitatory cells in a given layer to those in nearby layers (Xu et al., 2016Xu X. Olivas N.D. Ikrar T. Peng T. Holmes T.C. Nie Q. Shi Y. Primary visual cortex shows laminar-specific and balanced circuit organization of excitatory and inhibitory synaptic connectivity.J. Physiol. 2016; 594: 1891-1910Crossref PubMed Google Scholar). Ascending (left) and descending projections (right), with thicknesses proportional to excitatory connection strength. Laminae targeted by thalamic input shown in blue and red. Strength is shown in the illustration (C) and as a connectivity matrix (D), with pre- and postsynaptic layers labeled. (E) Local excitatory connectivity in L2/3 and L4. (A) For granular and supragranular layers, developmental changes in the connectivity of local circuits are illustrated. Excitatory neurons are illustrated in black. PV+ (blue), SST+ (burgundy), and VIP+ (green) inputs are color coded, along with neuromodulatory inputs such as acetylcholine (purple). Excitatory TC inputs are shown in black. Developmental age and time are annotated at the bottom. L4 changes in interneuron connectivity precede L2/3 changes (Jiang et al., 2010Jiang B. Sohya K. Sarihi A. Yanagawa Y. Tsumoto T. Laminar-specific maturation of GABAergic transmission and susceptibility to visual deprivation are related to endocannabinoid sensitivity in mouse visual cortex.J. Neurosci. 2010; 30: 14261-14272Crossref PubMed Scopus (33) Google Scholar), with PV maturation in L2/3 correlated in time to CP onset and closure (Fagiolini et al., 2004Fagiolini M. Fritschy J.M. Löw K. Möhler H. Rudolph U. Hensch T.K. Specific GABAA circuits for visual cortical plasticity.Science. 2004; 303: 1681-1683Crossref PubMed Scopus (332) Google Scholar). L2/3 connectivity matures during this period (Cossell et al., 2015Cossell L. Iacaruso M.F. Muir D.R. Houlton R. Sader E.N. Ko H. Hofer S.B. Mrsic-Flogel T.D. Functional organization of excitatory synaptic strength in primary visual cortex.Nature. 2015; 518: 399-403Crossref PubMed Scopus (191) Google Scholar, Ko et al., 2013Ko H. Cossell L. Baragli C. Antolik J. Clopath C. Hofer S.B. Mrsic-Flogel T.D. The emergence of functional microcircuits in visual cortex.Nature. 2013; 496: 96-100Crossref PubMed Scopus (198) Google Scholar). SST+ connectivity to PV+ neurons, initially strong, grows weaker during this time and loses sensitivity to cholinergic modulation (Yaeger et al., 2019Yaeger C.E. Ringach D.L. Trachtenberg J.T. Neuromodulatory control of localized dendritic spiking in critical period cortex.Nature. 2019; 567: 100-104Crossref PubMed Scopus (14) Google Scholar). (B) Mature connectivity is summarized. The visual pathway of mammals begins in the retina, with retinal ganglion cell (RGC) projections that target a number of subcortical regions, including the superior colliculus (SC), dorsal lateral geniculate nucleus (dLGN), and suprachiasmatic nucleus (SCN; Figures 1A–1C). Blue and red in the figure illustrate projections corresponding to ipsilateral and contralateral eyes, with eye-specific segregation in mouse dLGN. In the mouse, the ipsilateral projection to dLGN is a small rounded patch surrounded by a larger area of contralateral input. Some binocular overlap in the mouse dLGN also exists (Figure 1B; Howarth et al., 2014Howarth M. Walmsley L. Brown T.M. Binocular integration in the mouse lateral geniculate nuclei.Curr. Biol. 2014; 24: 1241-1247Abstract Full Text Full Text PDF PubMed Google Scholar). The dLGN (Figure 2) can be subdivided into a core and shell region, with the core projecting principally to layer 4 (L4) of primary visual cortex (V1, also VISp in the reference atlas; Kuan et al., 2015Kuan L. Li Y. Lau C. Feng D. Bernard A. Sunkin S.M. Zeng H. Dang C. Hawrylycz M. Ng L. Neuroinformatics of the Allen Mouse Brain Connectivity Atlas.Methods. 2015; 73: 4-17Crossref PubMed Scopus (72) Google Scholar). The shell largely targets L1 (Cruz-Martín et al., 2014Cruz-Martín A. El-Danaf R.N. Osakada F. Sriram B. Dhande O.S. Nguyen P.L. Callaway E.M. Ghosh A. Huberman A.D. A dedicated circuit links direction-selective retinal ganglion cells to the primary visual cortex.Nature. 2014; 507: 358-361Crossref PubMed Scopus (151) Google Scholar). Higher-order visual thalamus, called the lateral posterior nucleus (LP) in mice (similar to the pulvinar of primates), projects strongly to L1, with some input to deeper layers, including L5A. The laminar structure of LP output may vary across visual areas (Bennett et al., 2019Bennett C. Gale S.D. Garrett M.E. Newton M.L. Callaway E.M. Murphy G.J. Olsen S.R. Higher-Order Thalamic Circuits Channel Parallel Streams of Visual Information in Mice.Neuron. 2019; 102: 477-492.e5Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar). Two classes of dLGN neurons are excitatory TC neurons and intrinsic GABAergic interneurons, in which the former outnumber the latter ∼4:1. Intrinsic interneurons make dendrodendritic and axodendritic inhibitory connections onto TC neurons and other dLGN interneurons (triads; Bickford et al., 2010Bickford M.E. Slusarczyk A. Dilger E.K. Krahe T.E. Kucuk C. Guido W. Synaptic development of the mouse dorsal lateral geniculate nucleus.J. Comp. Neurol. 2010; 518: 622-635Crossref PubMed Scopus (52) Google Scholar, Morgan et al., 2016Morgan J.L. Berger D.R. Wetzel A.W. Lichtman J.W. The Fuzzy Logic of Network Connectivity in Mouse Visual Thalamus.Cell. 2016; 165: 192-206Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar, Rafols and Valverde, 1973Rafols J.A. Valverde F. The structure of the dorsal lateral geniculate nucleus in the mouse. A Golgi and electron microscopic study.J. Comp. Neurol. 1973; 150: 303-332Crossref PubMed Google Scholar). These two cell types receive excitatory RGC and corticothalamic (CT) inputs as well as inhibitory inputs from thalamic reticular neurons (TRNs). TC neurons, also called relay neurons, project to the cortex, sending collaterals to TRN. Interneurons in the thalamic reticular nucleus are parvalbumin positive (PV+), whereas intrinsic interneurons are largely PV−, although detailed characterization is not complete (Kalish et al., 2018Kalish B.T. Cheadle L. Hrvatin S. Nagy M.A. Rivera S. Crow M. Gillis J. Kirchner R. Greenberg M.E. Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement.Proc. Natl. Acad. Sci. USA. 2018; 115: E1051-E1060Crossref PubMed Scopus (17) Google Scholar). CT inputs, in turn, also send collaterals to TRNs. This circuit integrates, modifies, and relays visual information passing from the retina to V1. Experience-Dependent Plasticity in the Thalamus. In the cat, studies revealed much more plasticity in cortical than in dLGN circuits (Wiesel and Hubel, 1963aWiesel T.N. Hubel D.H. Single-cell responses in striate cortex of kittens deprived of vision in one eye.J. Neurophysiol. 1963; 26: 1003-1017Crossref PubMed Scopus (1751) Google Scholar). MD leads to the shrinkage of TC neuron somata in dLGN, but to little change in OD (Sherman and Spear, 1982Sherman S.M. Spear P.D. Organization of visual pathways in normal and visually deprived cats.Physiol. Rev. 1982; 62: 738-855Crossref PubMed Scopus (493) Google Scholar, Wiesel and Hubel, 1963bWiesel T.N. Hubel D.H. Effects of Visual Deprivation on Morphology and Physiology of Cells in the Cats Lateral Geniculate Body.J. Neurophysiol. 1963; 26: 978-993Crossref PubMed Scopus (797) Google Scholar). MD also has little effect on eye-specific segregation in mice (Guzik-Kornacka et al., 2016Guzik-Kornacka A. van der Bourg A. Vajda F. Joly S. Christ F. Schwab M.E. Pernet V. Nogo-A deletion increases the plasticity of the optokinetic response and changes retinal projection organization in the adult mouse visual system.Brain Struct. Funct. 2016; 221: 317-329Crossref PubMed Scopus (10) Google Scholar). These studies led to the view that CP plasticity was predominantly a cortical phenomenon. In contrast to the cat, studies have uncovered more plasticity in the mouse thalamus than previously recognized. The traditional view divides dLGN into distinct eye-specific territories, with a predominantly contralateral area and a much smaller ipsilateral region. However, in vivo recordings from dorsomedial dLGN show a significant number of TC neurons that are responsive to binocular stimulation, indicating that convergent retinal inputs from both eyes are present in adult mice (Howarth et al., 2014Howarth M. Walmsley L. Brown T.M. Binocular integration in the mouse lateral geniculate nuclei.Curr. Biol. 2014; 24: 1241-1247Abstract Full Text Full Text PDF PubMed Google Scholar). These findings suggest that some TC neurons in the ipsilateral patch extend dendrites into the contralateral dLGN layer (Krahe et al., 2011Krahe T.E. El-Danaf R.N. Dilger E.K. Henderson S.C. Guido W. Morphologically distinct classes of relay cells exhibit regional preferences in the dorsal lateral geniculate nucleus of the mouse.J. Neurosci. 2011; 31: 17437-17448Crossref PubMed Scopus (57) Google Scholar). Moreover, MD during the developmental window corresponding to the OD cortical CP described below (∼P18–P32) shifts the relative TC neuron response magnitude evoked by the contralateral and ipsilateral eye. This thalamic plasticity depends on the GABAA receptor α1 subunit (Sommeijer et al., 2017Sommeijer J.P. Ahmadlou M. Saiepour M.H. Seignette K. Min R. Heimel J.A. Levelt C.N. Thalamic inhibition regulates critical-period plasticity in visual cortex and thalamus.Nat. 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