Plasticity In Visual Cortex Research Articles

Reduced visual acuity is mirrored in low vision imagery.

Research has examined the nature of visual imagery in normally sighted and blind subjects, but not in those with low vision. Findings with normally sighted subjects suggest that imagery involves primary visual areas of the brain. Since the plasticity of visual cortex appears to be limited in adulthood, we might expect imagery of those with adult-onset low vision to be relatively unaffected by these losses. But if visual imagery is based on recent and current experience, we would expect images of those with low vision to share some properties of impaired visual perception. We examined key parameters of mental images reported by normally sighted subjects, compared to those with early- and late-onset low vision, and with a group of subjects with restricted visual fields using an imagery questionnaire. We found evidence that those with reduced visual acuity report the imagery distances of objects to be closer than those with normal acuity and also depict objects in imagery with lower resolution than those with normal visual acuity. We also found that all low vision groups, like the normally sighted, image objects at a substantially greater distance than when asked to place them at a distance that 'just fits' their imagery field (overflow distance). All low vision groups, like the normally sighted, showed evidence of a limited visual field for imagery, but our group with restricted visual fields did not differ from the other groups in this respect. We conclude that imagery of those with low vision is similar to that of those with normal vision in being dependent on the size of objects or features being imaged, but that it also reflects their reduced visual acuity. We found no evidence for a dependence on imagery of age of onset or number of years of vision impairment.

Sleep is more than rest for plasticity in the human cortex.

Sleep promotes adaptation of behavior and underlying neural plasticity in comparison to active wakefulness. However, the contribution of its two main characteristics, sleep-specific brain activity and reduced stimulus interference, remains unclear. We tested healthy humans on a texture discrimination task, a proxy for neural plasticity in primary visual cortex, in the morning and retested them in the afternoon after a period of daytime sleep, passive waking with maximally reduced interference, or active waking. Sleep restored performance in direct comparison to both passive and active waking, in which deterioration of performance across repeated within-day testing has been linked to synaptic saturation in the primary visual cortex. No difference between passive and active waking was observed. Control experiments indicated that deterioration across wakefulness was retinotopically specific to the trained visual field and not due to unspecific performance differences. The restorative effect of sleep correlated with time spent in NREM sleep and with electroencephalographic slow wave energy, which is thought to reflect renormalization of synaptic strength. The results indicate that sleep is more than a state of reduced stimulus interference, but that sleep-specific brain activity restores performance by actively refining cortical plasticity.

Transcranial direct current stimulation induces long-term potentiation-like plasticity in the human visual cortex

Transcranial direct current stimulation (tDCS) is increasingly used as a form of noninvasive brain stimulation to treat psychiatric disorders; however, its mechanism of action remains unclear. Prolonged visual stimulation (PVS) can enhance evoked EEG potentials (visually evoked potentials, VEPs) and has been proposed as a tool to examine long-term potentiation (LTP) in humans. The objective of the current study was to induce and analyze VEP plasticity and examine whether tDCS could either modulate or mimic plasticity changes induced by PVS. Thirty-eight healthy participants received tDCS, PVS, either treatment combined or neither treatment, with stimulation sessions being separated by one week. One session consisted of a baseline VEP measurement, one stimulation block, and six test VEP measurements. For PVS, a checkerboard reversal pattern was presented, and for tDCS, a constant current of 1 mA was applied via each bioccipital anodal target electrode for 10 min (Fig. S1). Both stimulation types decreased amplitudes of C1 compared to no stimulation (F = 10.1; p = 0.002) and led to a significantly smaller increase (PVS) or even decrease (tDCS) in N1 compared to no stimulation (F = 4.7; p = 0.034). While all stimulation types increased P1 amplitudes, the linear mixed effects model did not detect a significant difference between active stimulation and no stimulation. Combined stimulation induced sustained plastic modulation of C1 and N1 but with a smaller effect size than what would be expected for an additive effect. The results demonstrate that tDCS can directly induce LTP-like plasticity in the human cortex and suggest a mechanism of action of tDCS relying on the restoration of dysregulated synaptic plasticity in psychiatric disorders such as depression and schizophrenia.

The Spatiotemporal Organization of Experience Dictates Hippocampal Involvement in Primary Visual Cortical Plasticity

The hippocampus and neocortex are theorized to be crucial partners in the formation of long-term memories. Here, we assess hippocampal involvement in two related forms of experience-dependent plasticity in the primary visual cortex (V1) of mice. Like control animals, those with hippocampal lesions exhibit potentiation of visually evoked potentials following passive daily exposure to a phase reversing oriented grating stimulus, which is accompanied by long-term habituation of a reflexive behavioral response. Thus, low-level recognition memory is formed independently of the hippocampus. However, response potentiation resulting from daily exposure to a fixed sequence of four oriented gratings is severely impaired in mice with hippocampal damage. A feature of sequence plasticity in V1 of controls, but absent in lesioned mice, is generation of predictive responses to an anticipated stimulus element when it is withheld or delayed. Thus, hippocampus is involved in encoding temporally structured experience, even within primary sensory cortex.

Chondroitinase and Antidepressants Promote Plasticity by Releasing TRKB from Dephosphorylating Control of PTPσ in Parvalbumin Neurons.

Perineuronal nets (PNNs) are an extracellular matrix structure rich in chondroitin sulfate proteoglycans (CSPGs), which preferentially encase parvalbumin-containing (PV+) interneurons. PNNs restrict cortical network plasticity but the molecular mechanisms involved are unclear. We found that reactivation of ocular dominance plasticity in the adult visual cortex induced by chondroitinase ABC (chABC)-mediated PNN removal requires intact signaling by the neurotrophin receptor TRKB in PV+ neurons. Additionally, we demonstrate that chABC increases TRKB phosphorylation (pTRKB), while PNN component aggrecan attenuates brain-derived neurotrophic factor (BDNF)-induced pTRKB in cortical neurons in culture. We further found that protein tyrosine phosphatase σ (PTPσ, PTPRS), receptor for CSPGs, interacts with TRKB and restricts TRKB phosphorylation. PTPσ deletion increases phosphorylation of TRKB in vitro and in vivo in male and female mice, and juvenile-like plasticity is retained in the visual cortex of adult PTPσ-deficient mice (PTPσ+/−). The antidepressant drug fluoxetine, which is known to promote TRKB phosphorylation and reopen critical period-like plasticity in the adult brain, disrupts the interaction between TRKB and PTPσ by binding to the transmembrane domain of TRKB. We propose that both chABC and fluoxetine reopen critical period-like plasticity in the adult visual cortex by promoting TRKB signaling in PV+ neurons through inhibition of TRKB dephosphorylation by the PTPσ-CSPG complex.SIGNIFICANCE STATEMENT Critical period-like plasticity can be reactivated in the adult visual cortex through disruption of perineuronal nets (PNNs) by chondroitinase treatment, or by chronic antidepressant treatment. We now show that the effects of both chondroitinase and fluoxetine are mediated by the neurotrophin receptor TRKB in parvalbumin-containing (PV+) interneurons. We found that chondroitinase-induced visual cortical plasticity is dependent on TRKB in PV+ neurons. Protein tyrosine phosphatase σ (PTPσ, PTPRS), a receptor for PNNs, interacts with TRKB and inhibits its phosphorylation, and chondroitinase treatment or deletion of PTPσ increases TRKB phosphorylation. Antidepressant fluoxetine disrupts the interaction between TRKB and PTPσ, thereby increasing TRKB phosphorylation. Thus, juvenile-like plasticity induced by both chondroitinase and antidepressant treatment is mediated by TRKB activation in PV+ interneurons.

Deficits in higher visual area representations in a mouse model of Angelman syndrome

BackgroundSensory processing deficits are common in individuals with neurodevelopmental disorders. One hypothesis is that deficits may be more detectable in downstream, “higher” sensory areas. A mouse model of Angelman syndrome (AS), which lacks expression of the maternally inherited Ube3a allele, has deficits in synaptic function and experience-dependent plasticity in the primary visual cortex. Thus, we hypothesized that AS model mice have deficits in visually driven neuronal responsiveness in downstream higher visual areas (HVAs).MethodsHere, we used intrinsic signal optical imaging and two-photon calcium imaging to map visually evoked neuronal activity in the primary visual cortex and HVAs in response to an array of stimuli.ResultsWe found a highly specific deficit in HVAs. Drifting gratings that changed speed caused a strong response in HVAs in wildtype mice, but this was not observed in littermate AS model mice. Further investigation with two-photon calcium imaging revealed the effect to be largely driven by aberrant responses of inhibitory interneurons, suggesting a cellular basis for higher level, stimulus-selective cortical dysfunction in AS.ConclusionAssaying downstream, or “higher” circuitry may provide a more sensitive measure for circuit dysfunction in mouse models of neurodevelopmental disorders.Trial registrationNot applicable.

Do visual and auditory stimulus-specific response modulation reflect different mechanisms of neocortical plasticity?

Stimulus response modulation (SRM) of sensory evoked potentials represents a promising method as a non-invasive index of long-term potentiation (LTP)-like synaptic plasticity in the human sensory cortices. As of today, however, no consensus exists regarding which experimental parameters elicit the most robust SRM response. The aim of the current study was twofold; firstly, we aimed to replicate former studies demonstrating visual SRM in healthy adults. Second, we integrated visual and auditory stimuli within the same SRM recording session to assay potential cross-modal associations. Such an association between modalities would strengthen the assumption that the SRM effect reflects common mechanisms underlying synaptic plasticity rather than reflecting modality-specific phenomena. A replication of previous findings showing robust potentiation of the visual evoked potential was evident, supporting the majority of previous work using similar paradigms, lending further support to the notion that high-frequent visual stimulation is a viable probe into LTP-like synaptic plasticity in the human visual cortex. The auditory evoked potentials (AEPs) did not, however, fully replicate previous work, though a significant increase of temporally later AEP components was found. In contrast to our hypothesis, there were no significant within-subject cross-modality correlations between the visual and auditory SRM. This lack of significant association might suggest that auditory and visual SRM depend on different mechanisms, and that further SRM studies on non-invasive LTP-like synaptic plasticity should focus on optimizing paradigms within the visual modality.

Neurogranin, Encoded by the Schizophrenia Risk Gene NRGN, Bidirectionally Modulates Synaptic Plasticity via Calmodulin-Dependent Regulation of the Neuronal Phosphoproteome

BackgroundNeurogranin (Ng), encoded by the schizophrenia risk gene NRGN, is a calmodulin-binding protein enriched in the postsynaptic compartments, and its expression is reduced in the postmortem brains of patients with schizophrenia. Experience-dependent translation of Ng is critical for encoding contextual memory, and Ng regulates developmental plasticity in the primary visual cortex during the critical period. However, the overall impact of Ng on the neuronal signaling that regulates synaptic plasticity is unknown. MethodsAltered Ng expression was achieved via virus-mediated gene manipulation in mice. The effect on long-term potentiation (LTP) was accessed using spike timing–dependent plasticity protocols. Quantitative phosphoproteomics analyses led to discoveries in significant phosphorylated targets. An identified candidate was examined with high-throughput planar patch clamp and was validated with pharmacological manipulation. ResultsNg bidirectionally modulated LTP in the hippocampus. Decreasing Ng levels significantly affected the phosphorylation pattern of postsynaptic density proteins, including glutamate receptors, GTPases, kinases, RNA binding proteins, selective ion channels, and ionic transporters, some of which highlighted clusters of schizophrenia- and autism-related genes. Hypophosphorylation of NMDA receptor subunit Grin2A, one significant phosphorylated target, resulted in accelerated decay of NMDA receptor currents. Blocking protein phosphatase PP2B activity rescued the accelerated NMDA receptor current decay and the impairment of LTP mediated by Ng knockdown, implicating the requirement of synaptic PP2B activity for the deficits. ConclusionsAltered Ng levels affect the phosphorylation landscape of neuronal proteins. PP2B activity is required for mediating the deficit in synaptic plasticity caused by decreasing Ng levels, revealing a novel mechanistic link of a schizophrenia risk gene to cognitive deficits.

Silent Synapse-Based Mechanisms of Critical Period Plasticity.

Critical periods are postnatal, restricted time windows of heightened plasticity in cortical neural networks, during which experience refines principal neuron wiring configurations. Here, we propose a model with two distinct types of synapses, innate synapses that establish rudimentary networks with innate function, and gestalt synapses that govern the experience-dependent refinement process. Nascent gestalt synapses are constantly formed as AMPA receptor-silent synapses which are the substrates for critical period plasticity. Experience drives the unsilencing and stabilization of gestalt synapses, as well as synapse pruning. This maturation process changes synapse patterning and consequently the functional architecture of cortical excitatory networks. Ocular dominance plasticity (ODP) in the primary visual cortex (V1) is an established experimental model for cortical plasticity. While converging evidence indicates that the start of the critical period for ODP is marked by the maturation of local inhibitory circuits, recent results support our model that critical periods end through the progressive maturation of gestalt synapses. The cooperative yet opposing function of two postsynaptic signaling scaffolds of excitatory synapses, PSD-93 and PSD-95, governs the maturation of gestalt synapses. Without those proteins, networks do not progress far beyond their innate functionality, resulting in rather impaired perception. While cortical networks remain malleable throughout life, the cellular mechanisms and the scope of critical period and adult plasticity differ. Critical period ODP is initiated with the depression of deprived eye responses in V1, whereas adult ODP is characterized by an initial increase in non-deprived eye responses. Our model proposes the gestalt synapse-based mechanism for critical period ODP, and also predicts a different mechanism for adult ODP based on the sparsity of nascent gestalt synapses at that age. Under our model, early life experience shapes the boundaries (the gestalt) for network function, both for its optimal performance as well as for its pathological state. Thus, reintroducing nascent gestalt synapses as plasticity substrates into adults may improve the network gestalt to facilitate functional recovery.

Activation of Somatostatin Interneurons by Nicotinic Modulator Lypd6 Enhances Plasticity and Functional Recovery in the Adult Mouse Visual Cortex.

The limitation of plasticity in the adult brain impedes functional recovery later in life from brain injury or disease. This pressing clinical issue may be resolved by enhancing plasticity in the adult brain. One strategy for triggering robust plasticity in adulthood is to reproduce one of the hallmark physiological events of experience-dependent plasticity observed during the juvenile critical period: to rapidly reduce the activity of parvalbumin (PV)-expressing interneurons and disinhibit local excitatory neurons. This may be achieved through the enhancement of local inhibitory inputs, particularly those of somatostatin (SST)-expressing interneurons. However, to date the means for manipulating SST interneurons for enhancing cortical plasticity in the adult brain are not known. We show that SST interneuron-selective overexpression of Lypd6, an endogenous nicotinic signaling modulator, enhances ocular dominance plasticity in the adult primary visual cortex (V1). Lypd6 overexpression mediates a rapid experience-dependent increase in the visually evoked activity of SST interneurons as well as a simultaneous reduction in PV interneuron activity and disinhibition of excitatory neurons. Recapitulating this transient activation of SST interneurons using chemogenetics similarly enhanced V1 plasticity. Notably, we show that SST-selective Lypd6 overexpression restores visual acuity in amblyopic mice that underwent early long-term monocular deprivation. Our data in both male and female mice reveal selective modulation of SST interneurons and a putative downstream circuit mechanism as an effective method for enhancing experience-dependent cortical plasticity as well as functional recovery in adulthood.SIGNIFICANCE STATEMENT The decline of cortical plasticity after closure of juvenile critical period consolidates neural circuits and behavior, but this limits functional recovery from brain diseases and dysfunctions in later life. Here we show that activation of cortical somatostatin (SST) interneurons by Lypd6, an endogenous modulator of nicotinic acetylcholine receptors, enhances experience-dependent plasticity and recovery from amblyopia in adulthood. This manipulation triggers rapid reduction of PV interneuron activity and disinhibition of excitatory neurons, which are known hallmarks of cortical plasticity during juvenile critical periods. Our study demonstrates modulation of SST interneurons by Lypd6 to achieve robust levels of cortical plasticity in the adult brain and may provide promising targets for restoring brain function in the event of brain trauma or disease.

Identification of cofilin 1 as a candidate protein associated to mouse visual cortex plasticity

In order to characterize the mechanisms controlling plasticity in the mouse visual cortex, we used, for the first time on brain samples, an unconventional proteomic approach to separate acid-extracted proteins by bi-dimensional electrophoresis (AUT/SDS or AUT/AU gels). The analysis was performed on high plasticity critical period young vs. low plasticity adult, and on fluoxetine-induced high plasticity vs. low plasticity untreated adult mice. Mass spectrometry allowed for the identification of 11 proteins that are differentially expressed between critical period and adult mice, and 5 between fluoxetine-treated and control adult mice. We then focused on cofilin 1, as the intensity level of the corresponding spot on 2D gels was higher in both high plasticity conditions. Western blot showed that cofilin 1 expression is dynamically regulated during postnatal life, reaching a peak at the critical period, and decreasing at adult stage, and that it increases in fluoxetine-treated vs. untreated adult mice. In summary, by using a 2D gel electrophoresis differential approach on basic proteins followed by mass spectrometry and immunoblot analysis, we identified cofilin 1 as a potential candidate controlling plasticity levels of the mouse visual cortex.

Monocular Deprivation Affects Visual Cortex Plasticity Through cPKCγ-Modulated GluR1 Phosphorylation in Mice.

PurposeTo determine how visual cortex plasticity changes after monocular deprivation (MD) in mice and whether conventional protein kinase C gamma (cPKCγ) plays a role in visual cortex plasticity.MethodscPKCγ membrane translocation levels were quantified by using immunoblotting to explore the effects of MD on cPKCγ activation. Electrophysiology was used to record field excitatory postsynaptic potential (fEPSP) amplitude with the goal of observing changes in visual cortex plasticity after MD. Immunoblotting was also used to determine the phosphorylation levels of GluR1 at Ser831. Light transmission was analyzed using electroretinography to examine the effects of MD and cPKCγ on mouse retinal function.ResultsMembrane translocation levels of cPKCγ significantly increased in the contralateral visual cortex of MD mice compared to wild-type (WT) mice (P < 0.001). In the contralateral visual cortex, long-term potentiation (LTP) and the phosphorylation levels of GluR1 at Ser 831 were increased in cPKCγ+/+ mice after MD. Interestingly, these levels could be downregulated by cPKCγ knockout compared to cPKCγ+/++MD mice (P < 0.001). Compared to the right eyes of WT mice, the amplitudes of a-waves and b-waves declined in deprived right eyes of mice after MD (P < 0.001). There were no significant differences when comparing cPKCγ+/+ and cPKCγ−/− mice with MD.ConclusionscPKCγ participates in the plasticity of the visual cortex after MD, which is characterized by increased LTP in the contralateral visual cortex, which may be a result of cPKCγ-mediated phosphorylation of GluR1 at Ser 831.

Triple visual hemifield maps in a case of optic chiasm hypoplasia

In humans, each hemisphere comprises an overlay of two visuotopic maps of the contralateral visual field, one from each eye. Is the capacity of the visual cortex limited to these two maps or are plastic mechanisms available to host more maps? We determined the cortical organization of the visual field maps in a rare individual with chiasma hypoplasia, where visual cortex plasticity is challenged to accommodate three hemifield maps. Using high-resolution fMRI at 7T and diffusion-weighted MRI at 3T, we found three hemiretinal inputs, instead of the normal two, to converge onto the left hemisphere. fMRI-based population receptive field mapping of the left V1–V3 at 3T revealed three superimposed hemifield representations in the left visual cortex, i.e. two representations of opposing visual hemifields from the left eye and one right hemifield representation from the right eye. We conclude that developmental plasticity including the re-wiring of local intra- and cortico-cortical connections is pivotal to support the coexistence and functioning of three hemifield maps within one hemisphere.

Astrocytes shape the plastic response of adult cortical neurons to vision loss.

Astrocytes are vital for preserving correct brain functioning by continuously sustaining neuronal activity and survival. They are in contact with multiple synapses at once allowing the expansion of local synaptic events into activity changes in neuronal networks. Furthermore, cortical astrocytes integrate local sensory inputs and behavioral state. From an anatomical, molecular, and functional perspective, astrocytes are thus ideal candidates to influence complex large-scale brain mechanisms such as plasticity. We collected evidence for the astrocytic potential for plasticity modulation, using the monocular enucleation (ME) mouse model of visual cortex plasticity. The impact of one-eyed vision involves the functional recruitment of the deprived visual cortex by the spared senses within a 7-week time frame, reflecting a substantial change in sensory information processing. In visually deprived cortex, a swift upregulation in Aldh1l1-positive astrocyte density lasts until maximal functional recovery is reached. Transient metabolic silencing of visual cortex astrocytes at the time of ME induction, through intracranial fluorocitrate injections, reveals that astrocytes are required on site to achieve adequate long-term neuronal reactivation. In addition, chronic stimulation by Gi but not Gq G-protein coupled receptor activation of local astrocytes boosts the cortical plasticity phenomenon. Hence, functional manipulation of protoplasmic astrocytes has long-lasting effects on the functional recovery of cortical neurons upon sensory loss, possibly by influencing the neuronal threshold to reactivate. Together, our results highlight an integral role for astrocytes in mediating adult cortical plasticity and unmask astrocyte specific Gi signaling as an interesting therapeutic pathway for brain plasticity regulation.

Opposing Somatic and Dendritic Expression of Stimulus-Selective Response Plasticity in Mouse Primary Visual Cortex.

Daily exposure of awake mice to a phase-reversing visual grating stimulus leads to enhancement of the visual-evoked potential (VEP) in layer 4 of the primary visual cortex (V1). This stimulus-selective response potentiation (SRP) resembles and shares mechanistic requirements with canonical long-term synaptic potentiation (LTP). However, it remains to be determined how this augmentation of a population response translates into altered neuronal activity of individual V1 neurons. To address this question, we performed longitudinal calcium imaging of layer 4 excitatory neurons in V1 and tracked changes associated with the induction and expression of SRP. We found no evidence for a net change in the fraction of visually responsive neurons as the stimulus became familiar. However, endoscopic calcium imaging of layer 4 principal neurons revealed that somatic calcium transients in response to phase-reversals of the familiar visual stimulus are reduced and undergo strong within-session adaptation. Conversely, neuropil calcium responses and VEPs are enhanced during familiar stimulus viewing, and the VEPs show reduced within-session adaptation. Consistent with the exquisite selectivity of SRP, the plasticity of cellular responses to phase-reversing gratings did not translate into altered orientation selectivity to drifting gratings. Our findings suggest a model in which augmentation of fast, short-latency synaptic (dendritic) responses, manifested as enhanced layer 4 VEPs, recruits inhibition to suppress cellular activity. Reduced cellular activity to the familiar stimulus may account for the behavioral correlate of SRP, orientation-selective long-term habituation.

Preservation of Visual Cortex Plasticity in Retinitis Pigmentosa

Retinitis Pigmentosa (RP) is a class of inherited disorders caused by the progressive death of photoreceptors in the retina. RP is still orphan of an effective treatment, with increasing optimism deriving from research aimed at arresting neurodegeneration or replacing light-responsive elements. All these therapeutic strategies rely on the functional integrity of the visual system downstream of photoreceptors. Whereas the inner retinal structure and optic radiation are known to be considerably preserved at least in early stages of RP, very little is known about the visual cortex. Remarkably, it remains completely unclear whether visual cortex plasticity is still present in RP. Using a well-established murine model of RP, the rd10 mouse, we report that visual cortical circuits retain high levels of plasticity, preserving their capability of input-dependent remodelling even at a late stage of retinal degeneration.

Homeostatic regulation of perisynaptic matrix metalloproteinase 9 (MMP9) activity in the amblyopic visual cortex.

Dark exposure (DE) followed by light reintroduction (LRx) reactivates robust synaptic plasticity in adult mouse primary visual cortex (V1), which allows subsequent recovery from amblyopia. Previously we showed that perisynaptic proteolysis by MMP9 mediates the enhancement of plasticity by LRx in binocular adult mice (Murase et al., 2017). However, it was unknown if a visual system compromised by amblyopia could engage this pathway. Here we show that LRx to adult amblyopic mice induces perisynaptic MMP2/9 activity and extracellular matrix (ECM) degradation in deprived and non-deprived V1. Indeed, LRx restricted to the amblyopic eye is sufficient to induce robust MMP2/9 activity at thalamo-cortical synapses and ECM degradation in deprived V1. Two-photon live imaging demonstrates that the history of visual experience regulates MMP2/9 activity in V1, and that DE lowers the threshold for the proteinase activation. The homeostatic reduction of the MMP2/9 activation threshold by DE enables visual input from the amblyopic pathway to trigger robust perisynaptic proteolysis.

Ocular Dominance Plasticity in Binocular Primary Visual Cortex Does Not Require C1q.

C1q, the initiator of the classical complement cascade, mediates synapse elimination in the postnatal mouse dorsolateral geniculate nucleus of the thalamus and sensorimotor cortex. Here, we asked whether C1q plays a role in experience-dependent synaptic refinement in the visual system at later stages of development. The binocular zone of primary visual cortex (V1b) undergoes spine loss and changes in neuronal responsiveness following the closure of one eye during a defined critical period [a process referred to as ocular dominance plasticity (ODP)]. We therefore hypothesized that ODP would be impaired in the absence of C1q, and that V1b development would also be abnormal without C1q-mediated synapse elimination. However, when we examined several features of V1b development in mice lacking C1q, we found that the densities of most spine populations on basal and proximal apical dendrites, as well as firing rates and ocular dominance, were normal. C1q was only transiently required for the development of spines on apical, but not basal, secondary dendrites. Dendritic morphologies were also unaffected. Although we did not observe the previously described spine loss during ODP in either genotype, our results reveal that the animals lacking C1q had normal shifts in neuronal responsiveness following eye closure. Experiments were performed in both male and female mice. These results suggest that the development and plasticity of the mouse V1b is grossly normal in the absence of C1q.SIGNIFICANCE STATEMENT These findings illustrate that the development and experience-dependent plasticity of V1b is mostly normal in the absence of C1q, even though C1q has previously been shown to be required for developmental synapse elimination in the mouse visual thalamus as well as sensorimotor cortex. The V1b phenotypes in mice lacking C1q are more similar to the mild defects previously observed in the hippocampus of these mice, emphasizing that the contribution of C1q to synapse elimination appears to be dependent on context.

Microglial mechanisms of experience-dependent plasticity in the mouse visual cortex

Microglial mechanisms of experience-dependent plasticity in the mouse visual cortex

17\u03b1 Estradiol promotes plasticity of spared inputs in the adult amblyopic visual cortex

The promotion of structural and functional plasticity by estrogens is a promising approach to enhance central nervous system function in the aged. However, how the sensitivity to estrogens is regulated across brain regions, age and experience is poorly understood. To ask if estradiol treatment impacts structural and functional plasticity in sensory cortices, we examined the acute effect of 17α-Estradiol in adult Long Evans rats following chronic monocular deprivation, a manipulation that reduces the strength and selectivity of deprived eye vision. Chronic monocular deprivation decreased thalamic input from the deprived eye to the binocular visual cortex and accelerated short-term depression of the deprived eye pathway, but did not change the density of excitatory synapses in primary visual cortex. Importantly, we found that the classical estrogen receptors ERα and ERβ were robustly expressed in the adult visual cortex, and that a single dose of 17α-Estradiol reduced the expression of the calcium-binding protein parvalbumin, decreased the integrity of the extracellular matrix and increased the size of excitatory postsynaptic densities. Furthermore, 17α-Estradiol enhanced experience-dependent plasticity in the amblyopic visual cortex, by promoting response potentiation of the pathway served by the non-deprived eye. The promotion of plasticity at synapses serving the non-deprived eye may reflect selectivity for synapses with an initially low probability of neurotransmitter release, and may inform strategies to remap spared inputs around a scotoma or a cortical infarct.