Period For Ocular Dominance Plasticity Research Articles

A developmental critical period for ocular dominance plasticity of binocular neurons in mouse superior colliculus

Detecting visual features in the environment is crucial for animals' survival. The superior colliculus (SC) is implicated in motion detection and processing, whereas how the SC integrates visual inputs from the two eyes remains unclear. Using invivo electrophysiology, we show that mouse SC contains many binocular neurons that display robust ocular dominance (OD) plasticity in a critical period during early development, which is similar to, but not dependent on, the primary visual cortex. NR2A- and NR2B-containing N-methyl-D-aspartate (NMDA) receptors play an essential role in the regulation of SC plasticity. Blocking NMDA receptors can largely prevent the impairment of predatory hunting caused by monocular deprivation, indicating that maintaining the binocularity of SC neurons is required for efficient hunting behavior. Together, our studies reveal the existence and function of OD plasticity in SC, which broadens our understanding of the development of subcortical visual circuitry relating to motion detection and predatory hunting.

Invited Session IV: Studies of the visual cortex with sub-millimeter resolution: Development of natural scene processing continues after the critical period for ocular dominance plasticity closes.

The development of the visual system is known to be shaped by early-life experience. How complex responses to naturalistic scenes emerge from neurons that are innately tuned to simple orientations is an active area of investigation. Using 2-photon calcium in awake mice, we found that natural scene discriminability increases by 75% between the ages of 4 to 6 weeks in primary visual cortex. This increase in decoding accuracy is accompanied by a shift in neuronal preference towards natural scenes. Natural scene discriminability, therefore, continues to improve past the peak of the critical period for ocular dominance plasticity at postnatal day (p) 28. Notably visual deprivation specifically from p28 to p42 interfered with the full development of this preference shift and impaired natural scene decoding accuracy. We are currently exploring the circuit basis for this protracted development. We speculate that a sequential progression in which neurons first prefer simple stimuli such as oriented bars of light (grating stimuli) prior to the development of selectivity for complex features may help ensure that the spatial organization of receptive fields is maintained as the system becomes refined to represent salient visual cues as animals expand their behavioral repertoire and learn to navigate complex environments.

Development of myelin in fetal and postnatal neocortex of the pig, the European wild boar Sus scrofa

Myelination of the neocortex of altricial species is mostly a postnatal event, and the appearance of myelin has been associated with the end of the critical period for ocular dominance plasticity in rodent visual cortex. Due to their precocality, ungulates may tell a different story. Here, we analyzed the development of PDGFRα positive oligodendrocyte precursor cells and expression of myelin proteins in the laminar compartments of fetal and postnatal porcine cortex from E45 onwards. Precursor cell density initially increased and then decreased but remained present at P90. MAG and MBP staining were detectable at E70 in subventricular zone and deep white matter, ascending into gyral white matter at E85, and into the gray matter and marginal zone at E100 (birth in pig at E114). Protein blots confirmed the declining expression of PDGFRα from E65 onwards, and the increase of MBP and MAG expression from E80 onwards. Somatosensory input elicited by spontaneous activity is considered important for the formation of the body representation. Indeed, PDGFRα, MBP and MAG expression started earlier in somatosensory than in visual cortex. Taken together, myelination proceeded in white and gray matter and marginal zone of pig cortex before birth with an areal-specific time course, and an almost mature pattern was present at P5 in visual cortex.

Juvenile Shank3 KO Mice Adopt Distinct Hunting Strategies during Prey Capture Learning.

Mice are opportunistic omnivores that readily learn to hunt and eat insects such as crickets. The details of how mice learn these behaviors and how these behaviors may differ in strains with altered neuroplasticity are unclear. We quantified the behavior of juvenile wild-type (WT) and Shank3 knock-out (KO) mice as they learned to hunt crickets during the critical period for ocular dominance plasticity. This stage involves heightened cortical plasticity including homeostatic synaptic scaling, which requires Shank3, a glutamatergic synaptic protein that, when mutated, produces Phelan-McDermid syndrome and is often comorbid with autism spectrum disorder (ASD). Both strains showed interest in examining live and dead crickets and learned to hunt. Shank3 knock-out mice took longer to become proficient, and, after 5 d, did not achieve the efficiency of wild-type mice in either time-to-capture or distance-to-capture. Shank3 knock-out mice also exhibited different characteristics when pursuing crickets that could not be explained by a simple motor deficit. Although both genotypes moved at the same average speed when approaching a cricket, Shank3 KO mice paused more often, did not begin final accelerations toward crickets as early, and did not close the distance gap to the cricket as quickly as wild-type mice. These differences in Shank3 KO mice are reminiscent of some behavioral characteristics of individuals with ASD as they perform complex tasks, such as slower action initiation and completion. This paradigm will be useful for exploring the neural circuit mechanisms that underlie these learning and performance differences in monogenic ASD rodent models.

Differentiation of Hebbian and homeostatic plasticity mechanisms within layer 5 visual cortex neurons.

Cortical layer 5 contains two major types of projection neuron known as IB (intrinsic bursting) cells that project sub-cortically and RS (regular spiking) cells that project between cortical areas. This study describes the plasticity properties of RS and IB cells in the mouse visual cortex during the critical period for ocular dominance plasticity. We find that RS neurons exhibit synaptic depression in response to both dark exposure (DE) and monocular deprivation (MD), and their homeostatic recovery from depression is dependent on TNF-α. In contrast, IB cells demonstrate opposite responses to DE and MD, potentiating to DE and depressing to MD. IB cells' potentiation depends on CaMKII-autophosphorylation and not TNF-α. IB cells show mature synaptic properties at the start of the critical period while RS cells mature during the critical period. Together with observations in somatosensory cortex, these results suggest that differences in RS and IB plasticity mechanisms are a general cortical property.

Repeated maternal separation prolongs the critical period of ocular dominance plasticity in mouse visual cortex

In mammals, maternal separation has been reported to affect brain structure and function in various brain regions; however, its effect on visual system development is largely unknown. In this study, we established a repeated maternal separation (RMS) model in C57BL/6 mice, where the mice pups were separated from their mothers 1 h per day from postnatal day 2 to 8. Ocular dominance plasticity (ODP) was measured at different developmental ages. Interestingly, RMS delayed the opening of critical period (CP) of ODP in female, but not in male mice, while postponed the closure of CP in both sexes. Only female RMS mice maintained the juvenile-like ODP into adulthood. Neither the protein expressions of neither glutamate decarboxylase 65 (GAD65) nor N-methyl-D-aspartate receptor NR2B subunit were altered in visual cortex of RMS mice. No depression/anxiety-like behaviors were detected in RMS mice. These results for the first time reveal that RMS alters the development of ODP.

A Developmental Critical Period for Ocular Dominance Plasticity of Binocular Neurons in Mouse Superior Colliculus

A Developmental Critical Period for Ocular Dominance Plasticity of Binocular Neurons in Mouse Superior Colliculus

Sensitive timing of undifferentiation in oligodendrocyte progenitor cells and their enhanced maturation in primary visual cortex of binocularly enucleated mice.

Sensory experience modulates proliferation, differentiation, and migration of oligodendrocyte progenitor cells (OPCs). In the mouse primary visual cortex (V1), visual deprivation-dependent modulation of OPCs has not been demonstrated. Here, we demonstrate that undifferentiated OPCs developmentally peaked around postnatal day (P) 25, and binocular enucleation (BE) from the time of eye opening (P14-15) elevated symmetrically-divided undifferentiated OPCs in a reversible G0/G1 state even more at the bottom lamina of the cortex by reducing maturing oligodendrocyte (OL) lineage cells. Experiments using the sonic hedgehog (Shh) signaling inhibitor cyclopamine in vivo suggested that Shh signaling pathway was involved in the BE-induced undifferentiation process. The undifferentiated OPCs then differentiated within 5 days, independent of the experience, becoming mostly quiescent cells in control mice, while altering the mode of sister cell symmetry and forming quiescent as well as maturing cells in the enucleated mice. At P50, BE increased mature OLs via symmetric and asymmetric modes of cell segregation, resulting in more populated mature OLs at the bottom layer of the cortex. These data suggest that fourth postnatal week, corresponding to the early critical period of ocular dominance plasticity, is a developmentally sensitive period for OPC state changes. Overall, the visual loss promoted undifferentiation at the early period, but later increased the formation of mature OLs via a change in the mode of cell type symmetry at the bottom layer of mouse V1.

Ocular dominance columns in V1 are more susceptible than associated callosal patches to imbalance of eye input during precritical and critical periods.

In Long Evans rats, ocular dominance columns (ODCs) in V1 overlap with patches of callosal connections. Using anatomical tracers, we found that ODCs and callosal patches are present at postnatal day 10 (P10), several days before eye opening, and about 10 days before the activation of the critical period for ocular dominance plasticity (~P20). In rats monocularly enucleated at P10 and perfused ~P20, ODCs ipsilateral to the remaining eye desegregated, indicating that rat ODCs are highly susceptible to monocular enucleation during a precritical period. Monocular enucleation during the critical period exerted significant, although smaller, effects. Monocular eye lid suture during the critical period led to a significant expansion of the ipsilateral projection from the nondeprived eye, whereas the contralateral projection invaded into, and intermixed with, ipsilateral ODCs innervated by the deprived eye. We propose that this intermixing allows callosal connections to contribute to the effects of monocular deprivation assessed in the hemisphere ipsilateral to the nondeprived eye. The ipsilateral and contralateral projections from the deprived eye did not undergo significant shrinkage. In contrast, we found that callosal patches are less susceptible to imbalance of eye input. In rats monocularly enucleated during either the precritical or critical periods, callosal patches were maintained in the hemisphere ipsilateral to the remaining eye, but desegregated in the hemisphere ipsilateral to the enucleated orbit. Callosal patches were maintained in rats binocularly enucleated at P10 or later. Similarly, monocular deprivation during the critical period had no significant effect on callosal patches in either hemisphere.

Precise levels of nectin-3 are required for proper synapse formation in postnatal visual cortex

BackgroundDeveloping cortical neurons express a tightly choreographed sequence of cytoskeletal and transmembrane proteins to form and strengthen specific synaptic connections during circuit formation. Nectin-3 is a cell-adhesion molecule with previously described roles in synapse formation and maintenance. This protein and its binding partner, nectin-1, are selectively expressed in upper-layer neurons of mouse visual cortex, but their role in the development of cortical circuits is unknown.MethodsHere we block nectin-3 expression (via shRNA) or overexpress nectin-3 in developing layer 2/3 visual cortical neurons using in utero electroporation. We then assay dendritic spine densities at three developmental time points: eye opening (postnatal day (P)14), one week following eye opening after a period of heightened synaptogenesis (P21), and at the close of the critical period for ocular dominance plasticity (P35).ResultsKnockdown of nectin-3 beginning at E15.5 or ~ P19 increased dendritic spine densities at P21 or P35, respectively. Conversely, overexpressing full length nectin-3 at E15.5 decreased dendritic spine densities when all ages were considered together. The effects of nectin-3 knockdown and overexpression on dendritic spine densities were most significant on proximal secondary apical dendrites. Interestingly, an even greater decrease in dendritic spine densities, particularly on basal dendrites at P21, was observed when we overexpressed nectin-3 lacking its afadin binding domain.ConclusionThese data collectively suggest that the proper levels and functioning of nectin-3 facilitate normal synapse formation after eye opening on apical and basal dendrites in layer 2/3 of visual cortex.

Glomerulus-Selective Regulation of a Critical Period for Interneuron Plasticity in the Drosophila Antennal Lobe.

Several features of the adult nervous systems develop in a “critical period” (CP), during which high levels of plasticity allow neural circuits to be tuned for optimal performance. Through an analysis of long-term olfactory habituation (LTH) in female Drosophila, we provide new insight into mechanisms by which CPs are regulated in vivo. LTH manifests as a persistently reduced behavioral response to an odorant encountered for 4 continuous days and occurs together with the growth of specific, odorant-responsive glomeruli in the antennal lobe. We show that the CP for behavioral and structural plasticity induced by ethyl butyrate (EB) or carbon dioxide (CO2) closes within 48 h after eclosion. The elaboration of excitatory projection neuron (PN) processes likely contribute to glomerular volume increases, as follows: both occur together and similarly require cAMP signaling in the antennal lobe inhibitory local interneurons. Further, the CP for structural plasticity could be extended beyond 48 h if EB- or CO2-responsive olfactory sensory neurons (OSNs) are silenced after eclosion; thus, OSN activity is required for closing the CP. Strikingly, silencing of glomerulus-selective OSNs extends the CP for structural plasticity only in respective target glomeruli. This indicates the existence of a local, short-range mechanism for regulating CP closure. Such a local mechanism for CP regulation can explain why plasticity induced by the odorant geranyl acetate (which is attractive) shows no CP although it involves the same core plasticity mechanisms as CO2 and EB. Local control of closure mechanisms during the critical period can potentially impart evolutionarily adaptive, odorant-specific features to behavioral plasticity.SIGNIFICANCE STATEMENT The critical period for plasticity represents a stage of life at which animals learn specific tasks or features with particular facility. This work provides fresh evidence that mechanisms for regulating critical periods are broadly conserved across evolution. Thus, a critical period for long-term olfactory habituation in Drosophila, which closes early in adulthood can, like the critical period for ocular dominance plasticity in mammals, be extended by blocking sensory neurons early in life. Further observations show that critical periods for plasticity can be regulated by spatially restricted mechanisms, potentially allowing varied critical periods for plasticity to stimuli of different ethological relevance.

Disruption of Critical Period Plasticity in a Mouse Model of Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a common monogenic neurodevelopmental disorder associated with physical and cognitive problems. The cognitive issues are thought to arise from increased release of the neurotransmitter GABA. Modulating the signaling pathways causing increased GABA release in a mouse model of NF1 reverts deficits in hippocampal learning. However, clinical trials based on these approaches have so far been unsuccessful. We therefore used a combination of slice electrophysiology, in vivo two-photon calcium imaging, and optical imaging of intrinsic signal in a mouse model of NF1 to investigate whether cortical development is affected in NF1, possibly causing lifelong consequences that cannot be rescued by reducing inhibition later in life. We find that, in NF1 mice of both sexes, inhibition increases strongly during the development of the visual cortex and remains high. While this increase in cortical inhibition does not affect spontaneous cortical activity patterns during early cortical development, the critical period for ocular dominance plasticity is shortened in NF1 mice due to its early closure but unaltered onset. Notably, after environmental enrichment, differences in inhibitory innervation and ocular dominance plasticity between NF1 mice and WT littermates disappear. These results provide the first evidence for critical period dysregulation in NF1 and suggest that treatments aimed at normalizing levels of inhibition will need to start at early stages of development.SIGNIFICANCE STATEMENT Neurofibromatosis type 1 is associated with cognitive problems for which no treatment is currently available. This study shows that, in a mouse model of neurofibromatosis type 1, cortical inhibition is increased during development and critical period regulation is disturbed. Rearing the mice in an environment that stimulates cognitive function overcomes these deficits. These results uncover critical period dysregulation as a novel mechanism in the pathogenesis of neurofibromatosis type 1. This suggests that targeting the affected signaling pathways in neurofibromatosis type 1 for the treatment of cognitive disabilities may have to start at a much younger age than has so far been tested in clinical trials.

Pull-push neuromodulation of cortical plasticity enables rapid bi-directional shifts in ocular dominance.

Neuromodulatory systems are essential for remodeling glutamatergic connectivity during experience-dependent cortical plasticity. This permissive/enabling function of neuromodulators has been associated with their capacity to facilitate the induction of Hebbian forms of long-term potentiation (LTP) and depression (LTD) by affecting cellular and network excitability. In vitro studies indicate that neuromodulators also affect the expression of Hebbian plasticity in a pull-push manner: receptors coupled to the G-protein Gs promote the expression of LTP at the expense of LTD, and Gq-coupled receptors promote LTD at the expense of LTP. Here we show that pull-push mechanisms can be recruited in vivo by pairing brief monocular stimulation with pharmacological or chemogenetical activation of Gs- or Gq-coupled receptors to respectively enhance or reduce neuronal responses in primary visual cortex. These changes were stable, inducible in adults after the termination of the critical period for ocular dominance plasticity, and can rescue deficits induced by prolonged monocular deprivation.

The developmental and experience-dependent expression of IGF-2 in mice visual cortex

The circuitry associated with the visual cortex is particularly sensitive to experiences during the early stages of life, which are collectively known as critical periods. Critical period of ocular dominance plasticity is regulated by both environmental and genetic factors. Previous studies demonstrated that IGF-1 significantly influenced the regulation of visual cortex synaptic plasticity. IGF-2 can reportedly regulate synapse formation, dendritic spine maturation, and memory consolidation in rodents. Association between IGF-2 and the regulation of visual cortex synaptic plasticity remains unclear. Here, we first aimed to elucidate the normal expression patterns of IGF-2 and its laminar expression pattern during the process of visual cortex development in mice. This confirmed that IGF-2 may influence the regulation of ocular dominance plasticity in mice. We further elucidated the role of IGF-2 in the regulation of visual cortex synaptic plasticity by examining the effect of monocular deprivation (MD) on IGF-2 expression in the visual cortex. Interestingly, we observed that MD remarkably reduced IGF-2 expression in the visual cortex. Rodents reared in an enriched environment, with enhanced sensory, motor, and social experiences, were capable of effectively accelerating the development of the visual system and could restore normal visual acuity. Although the enriched environment facilitated the restoration of normal visual acuity in the MD mice, IGF-2 expression levels in the visual cortex remained unchanged. Therefore, we considered the possibility that IGF-2 may have a different role with regard to the modulation of plasticity in the visual cortex of the mice, which we aim to study in the future.

Selective serotonin reuptake inhibitors for functional recovery after stroke: similarities with the critical period and the role of experience-dependent plasticity.

There has been a growing interest in the potential for plasticity-inducing pharmacological interventions to enhance post-stroke recovery. One group of drugs that continues to garner a great deal of attention in this regard is a class of antidepressants called the selective serotonin reuptake inhibitors. Here we propose a model for the mechanism by which these drugs may enhance plasticity after ischemic brain injury. First, we review the research in animal models demonstrating how selective serotonin reuptake inhibitors reopen the critical period for ocular dominance plasticity in adulthood. We then compare this period of heightened plasticity to the cellular and biochemical milieu of perilesional tissue after an ischemic event in the adult brain. We argue that selective serotonin reuptake inhibitors administered acutely after an ischemic stroke alter excitatory-inhibitory balance in perilesional tissue and reinstate a type of plasticity reminiscent of the critical period in development. Finally, we discuss opportunities for future research in this area in both the preclinical and clinical realms.

TrkB Activation during a Critical Period Mimics the Protective Effects of Early Visual Experience on Perception and the Stability of Receptive Fields in Adult Superior Colliculus.

During a critical period in development, spontaneous and evoked retinal activity shape visual pathways in an adaptive fashion. Interestingly, spontaneous activity is sufficient for spatial refinement of visual receptive fields (RFs) in superior colliculus (SC) and visual cortex (V1), but early visual experience is necessary to maintain inhibitory synapses and stabilize RFs in adulthood (Carrasco et al., 2005, 2011; Carrasco and Pallas, 2006; Balmer and Pallas, 2015a). In V1, BDNF and its high-affinity receptor TrkB are important for development of visual acuity, inhibition, and regulation of the critical period for ocular dominance plasticity (Hanover et al., 1999; Huang et al., 1999; Gianfranceschi et al., 2003). To examine the generality of this signaling pathway for visual system plasticity, the present study examined the role of TrkB signaling during the critical period for RF refinement in SC. Activating TrkB receptors during the critical period (P33-P40) in dark reared subjects produced normally refined RFs, and blocking TrkB receptors in light-exposed animals resulted in enlarged adult RFs like those in dark reared animals. We also report here that deprivation- or TrkB blockade-induced RF enlargement in adulthood impaired fear responses to looming overhead stimuli and negatively impacted visual acuity. Thus, early TrkB activation is both necessary and sufficient to maintain visual RF refinement, robust looming responses, and visual acuity in adulthood. These findings suggest a common signaling pathway exists for the maturation of inhibition between V1 and SC.SIGNIFICANCE STATEMENT Receptive field refinement in superior colliculus differs from more commonly studied examples of critical period plasticity in visual pathways in that it does not require visual experience to occur; rather, spontaneous activity is sufficient. Maintenance of refinement beyond puberty requires a brief, early exposure to light to stabilize the lateral inhibition that shapes receptive fields. We find that TrkB activation during a critical period can substitute for visual experience in maintaining receptive field refinement into adulthood, and that this maintenance is beneficial to visual survival behaviors. Thus, as in some other types of plasticity, TrkB signaling plays a crucial role in receptive field refinement.

Vesicular GABA Transporter Is Necessary for Transplant-Induced Critical Period Plasticity in Mouse Visual Cortex.

The maturation of GABAergic inhibitory circuits is necessary for the onset of the critical period for ocular dominance plasticity (ODP) in the postnatal visual cortex (Hensch, 2005; Espinosa and Stryker, 2012). When it is deficient, the critical period does not start. When inhibitory maturation or signaling is precocious, it induces a precocious critical period. Heterochronic transplantation of GABAergic interneuron precursors derived from the medial ganglionic eminence (MGE) can induce a second period of functional plasticity in the visual cortex (Southwell et al., 2010). Although the timing of MGE transplantation-induced plasticity is dictated by the maturation of the transplanted cells, its mechanisms remain largely unknown. Here, we sought to test the effect of blocking vesicular GABA loading and subsequent release by transplanted interneurons on the ability to migrate, integrate, and induce plasticity in the host circuitry. We show that MGE cells taken from male and female donors that lack vesicular GABA transporter (Vgat) expression disperse and differentiate into somatostatin- and parvalbumin-expressing interneurons upon heterochronic transplantation in the postnatal mouse cortex. Although transplanted Vgat mutant interneurons come to express mature interneuron markers and display electrophysiological properties similar to those of control cells, their morphology is significantly more complex. Significantly, Vgat mutant MGE transplants fail to induce ODP, demonstrating the pivotal role of vesicular GABAergic transmission for MGE transplantation-induced plasticity in the postnatal mouse visual cortex.SIGNIFICANCE STATEMENT Embryonic inhibitory neurons thrive when transplanted into postnatal brains, migrating and differentiating in the host as they would have done if left in the donor. Once integrated into the host, these new neurons can have profound effects. For example, in the visual cortex, such neurons induce a second critical period of activity-dependent plasticity when they reach the appropriate stage of development. The cellular mechanism by which these transplanted GABAergic interneurons induce plasticity is unknown. Here, we show that transplanted interneurons that are unable to fill synaptic vesicles with GABA migrate and integrate into the host circuit, but they do not induce a second period of plasticity. These data suggest a role for the vesicular GABA transporter in transplantation-mediated plasticity.

Binocular deprivation induces both age-dependent and age-independent forms of plasticity in parvalbumin inhibitory neuron visual response properties.

Activity of cortical inhibitory interneurons is rapidly reduced in response to monocular deprivation during the critical period for ocular dominance plasticity and in response to salient events encountered during learning. In the case of primary sensory cortex, a decrease in mean evoked firing rate of parvalbumin-positive (PV) inhibitory neurons is causally linked to a reorganization of excitatory networks following sensory perturbation. Converging evidence indicates that it is deprivation, and not an imbalance between open- and closed-eye inputs, that triggers rapid plasticity in PV neurons. However, this has not been directly tested in vivo. Using two-photon guided cell-attached recording, we examined the impact of closing both eyes for 24 h on PV neuron response properties in mouse primary visual cortex. We found that binocular deprivation induces a 30% reduction in stimulus-evoked mean firing rate and that this reduction is specific to critical period-aged mice. The number of PV neurons showing detectable tuning to orientation increased after 24 h of deprivation, and this effect was also specific to critical period-aged mice. In contrast to evoked mean firing rate and orientation tuning, measurements of trial-to-trial variability revealed that stimulus-driven decreases in variability are significantly dampened by deprivation during both the critical period and the postcritical period. These data establish that open-eye inputs are not required to drive deprivation-induced weakening of PV neuron evoked activity and that other aspects of in vivo PV neuron activity are malleable throughout life. NEW & NOTEWORTHY Parvalbumin-positive (PV) neurons in sensory cortex are generally considered to be mediators of experience-dependent plasticity, and their plasticity is restricted to the critical period. However, in regions outside of sensory cortex, accumulating evidence demonstrates that PV neurons are plastic in adults, raising the possibility that aspects of PV response properties may be plastic throughout life. Here we identify a feature of in vivo PV neuron activity that remains plastic past the critical period.

Layer-specific Developmental Changes in Excitation and Inhibition in Rat Primary Visual Cortex.

Cortical circuits are profoundly shaped by experience during postnatal development. The consequences of altered vision during the critical period for ocular dominance plasticity have been extensively studied in rodent primary visual cortex (V1). However, little is known about how eye opening, a naturally occurring event, influences the maturation of cortical microcircuits. Here we used a combination of slice electrophysiology and immunohistochemistry in rat V1 to ask whether manipulating the time of eye opening for 3 or 7 d affects cortical excitatory and inhibitory synaptic transmission onto excitatory neurons uniformly across layers or induces laminar-specific effects. We report that binocular delayed eye opening for 3 d showed similar reductions of excitatory and inhibitory synaptic transmission in layers 2/3, 4, and 5. Synaptic transmission recovered to age-matched control levels if the delay was prolonged to 7 d, suggesting that these changes were dependent on binocular delay duration. Conversely, laminar-specific and long-lasting effects were observed if eye opening was delayed unilaterally. Our data indicate that pyramidal neurons located in different cortical laminae have distinct sensitivity to altered sensory drive; our data also strongly suggest that experience plays a fundamental role in not only the maturation of synaptic transmission, but also its coordination across cortical layers.

Enhancement of visual cortex plasticity by dark exposure.

Dark rearing is known to delay the time course of the critical period for ocular dominance plasticity in the visual cortex. Recent evidence suggests that a period of dark exposure (DE) may enhance or reinstate plasticity even after closure of the critical period, mediated through modification of the excitatory–inhibitory balance and/or removal of structural brakes on plasticity. Here, we investigated the effects of a week of DE on the recovery from a month of monocular deprivation (MD) in the primary visual cortex (V1) of juvenile mice. Optical imaging of intrinsic signals revealed that ocular dominance in V1 of mice that had received DE recovered slightly more quickly than of mice that had not, but the level of recovery after three weeks was similar in both groups. Two-photon calcium imaging showed no significant difference in the recovery of orientation selectivity of excitatory neurons between the two groups. Parvalbumin-positive (PV+) interneurons exhibited a smaller ocular dominance shift during MD but again no differences in subsequent recovery. The percentage of PV+ cells surrounded by perineuronal nets, a structural brake on plasticity, was lower in mice with than those without DE. Overall, DE causes a modest enhancement of mouse visual cortex plasticity.This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.