Biology subjects

Stryker, M. P.

Publications and source records attributed to Stryker, M. P..

17 recordsLinked to original sources

bioRxiv2025

GABAergic signaling by VIP interneurons gates running-dependent visual recovery in the adult brain

Experience-dependent plasticity in the adult visual cortex is enhanced by locomotion, a process mediated by vasoactive intestinal peptide (VIP)-expressing interneurons. While VIP interneurons are known to signal through both Gamma-aminobutyric acid (GABA) and VIP peptide, the specific contributions of these pathways during different forms of plasticity remain unclear. Monocular deprivation (MD) in adult mice alters cortical responses, though more slowly and differently than during a critical period in early life. Here, we used two-photon calcium imaging in awake adult mice to dissect the roles of VIP and GABA release from VIP interneurons during adult MD and subsequent binocular recovery. We found comparable level of ocular dominance shifts after MD in mice deficient in either peptidergic or GABA signaling, but disrupting GABA signaling impaired recovery of binocular responses. We also showed that running preferentially enhances contralateral eye responses in binocular primary visual cortex. However, this eye-specific modulation of visual responses by running was altered during recovery from MD and was dependent on VIP signaling pathways. These findings highlight the GABA-mediated inhibition by VIP interneurons as a critical pathway for promoting visual restoration in the adult brain. Significance StatementUsing longitudinal two-photon imaging in awake adult mice with genetically altered signaling path-ways in VIP interneurons, we demonstrate that GABAergic, but not peptidergic, signaling from VIP interneurons is essential for the recovery of binocular vision following monocular deprivation. We further reveal that locomotion modulates cortical responses in an eye-specific manner, a property dynamically reshaped by plasticity and dependent on VIP interneuron function. These findings identify a discrete inhibitory circuit element that links behavioral state to sensory recovery and highlight GABA release from VIP cells as a potential therapeutic target for restoring visual function in adulthood.

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bioRxiv2024

Integration of Transplanted Interneurons Over a New Period of Ocular Dominance Plasticity in Adult Mouse Visual Cortex

Cortical interneurons play an important role in mediating the juvenile critical period for ocular dominance plasticity in the mouse primary visual cortex. Previously, we showed that transplantation of cortical interneurons derived from the medial ganglionic eminence (MGE) opens a robust period of ocular dominance plasticity 33-35 days after transplantation into neonatal host visual cortex. The plasticity can be induced by transplanting either PV or SST MGE-derived cortical interneurons; it requires transplanted interneurons to express the vesicular GABAergic transporter; and it is manifested by changes to the host visual circuit. Here, we show that transplantation of MGE-derived cortical interneurons into the adult host visual cortex also opens a period of ocular dominance plasticity. The transplanted interneurons must be active to induce plasticity, and the neuronal activity and tuning of visually evoked responses in transplanted and host PV and SST interneurons are modulated by the locomotor state of the host. We also show that changes in activity over the period of plasticity induction are different between PV and SST interneurons but similar between host and transplanted interneurons of each type. The present findings demonstrate that the transplant-induced plasticity generated in adult visual cortex has many features in common with the role of these interneurons during the normal, juvenile critical period.

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bioRxiv2024

Encoding manifolds constructed from grating responses organize responses to natural scenes in cortical visual areas

A challenge in sensory neuroscience is understanding how populations of neurons operate in concert to represent diverse stimuli. To meet this challenge, we have created ``encoding manifolds'' that reveal the overall responses of brain areas to diverse stimuli and organize individual neurons in stimulus-response coordinates according to their selectivity and response dynamics. Here we use encoding manifolds to compare the population-level encoding of primary visual cortex (VISp) with that of five higher visual areas (VISam, VISal, VISpm, VISlm, and VISrl), using data from the Allen Institute Visual Coding-Neuropixels dataset from the mouse. We show that the topology of the encoding manifold for VISp and for higher visual areas is continuous, with smooth coordinates along which stimulus selectivity and response dynamics are organized with layer and cell-type specificity. Surprisingly, the manifolds revealed novel relationships between how natural scenes are encoded relative to static gratings--a relationship conserved across visual areas. Namely, neurons preferring natural scenes preferred either low or high spatial frequency gratings, but not intermediate ones. Analyzing responses by cortical layer reveals a preference for gratings concentrated in layer 6, whereas preferences for natural scenes tended to be higher in layers 2/3 and 4. The results demonstrate how machine learning approaches can be used to organize and visualize the structure of sensory coding, thereby revealing novel relationships within and across brain areas and sensory stimuli.

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bioRxiv2023

Neurotrophin NT-4/5 Promotes Structural Changes in Neurons of the Developing Visual Cortex

Current hypotheses on the mechanisms underlying the development and plasticity of the ocular dominance system through competitive interactions between pathways serving the two eyes strongly suggest the involvement of neurotrophins and their high affinity receptors. In the cat, infusion of the tyrosine kinase B ligand (trkB), neurotrophin-4/5 (NT-4/5), abolishes ocular dominance plasticity that follows monocular deprivation (Gillespie et al., 2000), while tyrosine kinase A and C ligands (trkA and trkC) do not have this effect. One interpretation of this finding is that NT-4/5 causes overgrowth and sprouting of thalamocortical and/or corticocortical terminals, leading to promiscuous neuronal connections which override the experience-dependent fine tuning of connections based on correlated activity. The present study tested whether neurons in cortical regions infused with NT-4/5 showed anatomical changes compatible with this hypothesis. Cats at the peak of the critical period received chronic infusion NT-4/5 into visual cortical areas 17/18 via an osmotic minipump. Visual cortical neurons were labeled in fixed slices using the DiOlistics methods (Gan et al., 2000) and analyzed in confocal microsco-py. Infusion of NT-4/5 induced a significant increase of spine-like processes on primary dendrites and a distinctive sprouting of protuberances from neuronal somata in all layers. The increase of neuronal membrane was paralleled by an increase in density of the presynaptic marker synaptophysin in infused areas, suggesting an increase in the numbers of synapses. A contingent of these newly formed synapses may feed into inhibitory circuits, as suggested by an increase of GAD-65 immunostaining in NT-4/5 affected areas. These anatomical changes are consistent with the physiological changes in such animals, suggesting that excess trkB neurotrophin can stimulate the formation of promiscuous connections during the critical period.

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bioRxiv2023

Adolescent oligodendrogenesis and myelination restrict experience-dependent neuronal plasticity in adult visual cortex

BACKGROUNDDevelopmental myelination is a protracted process in the mammalian brain. One theory for why oligodendrocytes mature so slowly posits that myelination may stabilize neuronal circuits and temper neuronal plasticity as animals age. We tested this hypothesis in the visual cortex, which has a well-defined critical period for experience-dependent neuronal plasticity. OBJECTIVES/METHODSTo prevent myelin progression, we conditionally deleted Myrf, a transcription factor necessary for oligodendrocyte maturation, from oligodendrocyte precursor cells (Myrf cKO) in adolescent mice. To induce experience-dependent plasticity, adult control and Myrf cKO mice were monocularly deprived by eyelid suture. Functional and structural neuronal plasticity in the visual cortex were assessed in vivo by intrinsic signal optical imaging and longitudinal two photon imaging of dendritic spines, respectively. RESULTSDuring adolescence, visual experience modulated the rate of oligodendrocyte maturation in visual cortex. Myrf deletion from oligodendrocyte precursors during adolescence led to inhibition of oligodendrocyte maturation and myelination that persisted into adulthood. Following monocular deprivation, visual cortex activity in response to visual stimulation of the deprived eye remained stable in adult control mice, as expected for post-critical period animals. By contrast, visual cortex responses to the deprived eye decreased significantly following monocular deprivation in adult Myrf cKO mice, reminiscent of the plasticity observed in adolescent mice. Furthermore, visual cortex neurons in adult Myrf cKO mice had fewer dendritic spines and a higher level of spine turnover. Finally, monocular deprivation induced spatially coordinated spine size decreases in adult Myrf cKO, but not control, mice. CONCLUSIONSThese results demonstrate a critical role for oligodendrocytes in shaping the maturation and stabilization of cortical circuits and support the concept of myelin acting as a brake on neuronal plasticity during development.

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bioRxiv2023

Population encoding of stimulus features along the visual hierarchy

The retina and primary visual cortex (V1) both exhibit diverse neural populations sensitive to diverse visual features. Yet it remains unclear how neural populations in each area partition stimulus space to span these features. One possibility is that neural populations are organized into discrete groups of neurons, with each group signaling a particular constellation of features. Alternatively, neurons could be continuously distributed across feature-encoding space. To distinguish these possibilities, we presented a battery of visual stimuli to mouse retina and V1 while measuring neural responses with multi-electrode arrays. Using machine learning approaches, we developed a manifold embedding technique that captures how neural populations partition feature space and how visual responses correlate with physiological and anatomical properties of individual neurons. We show that retinal populations discretely encode features, while V1 populations provide a more continuous representation. Applying the same analysis approach to convolutional neural networks that model visual processing, we demonstrate that they partition features much more similarly to the retina, indicating they are more like big retinas than little brains.

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bioRxiv2023

Stimulus-specific enhancement of responses in mouse primary visual cortex mediated by GABA release from VIP cells

When adult mice are repeatedly exposed to a particular visual stimulus for as little as one hour per day for several days while their visual cortex (V1) is in the high-gain state produced by locomotion, that specific stimulus elicits much stronger responses in V1 neurons for the following several weeks, even when measured in anesthetized animals. Such stimulus-specific enhancement (SSE) is not seen if locomotion is prevented. The effect of locomotion on cortical responses is mediated by vasoactive intestinal peptide (VIP) positive interneurons, which can release both the peptide and the inhibitory neurotransmitter GABA. Here we used genetic ablation to determine which of those molecules secreted by VIP-ergic neurons is responsible for SSE. SSE was not impaired by VIP deletion but was prevented by compromising release of GABA from VIP cells. This finding suggests that SSE may result from Hebbian mechanisms that remain present in adult V1. SIGNIFICANCEMany neurons package and release a peptide along with a conventional neurotransmitter. The conventional view is that such peptides exert late, slow effects on plasticity. We studied a form of cortical plasticity that depends on the activity of neurons that express both vasoactive intestinal peptide (VIP) and the inhibitory neurotransmitter GABA. GABA release accounted for their action on plasticity, with no effect of deleting the peptide on this phenomenon.

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bioRxiv2023

The Clustered Gamma Protocadherin Pcdhγc4 Isoform Regulates Cortical Interneuron Programmed Cell Death in the Mouse Cortex.

Cortical function critically depends on inhibitory/excitatory balance. Cortical inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into cortex, where their numbers are adjusted by programmed cell death. Previously, we showed that loss of clustered gamma protocadherins (Pcdh{gamma}), but not of genes in the alpha or beta clusters, increased dramatically cIN BAX-dependent cell death in mice. Here we show that the sole deletion of the Pcdh{gamma}c4 isoform, but not of the other 21 isoforms in the Pcdh{gamma} gene cluster, increased cIN cell death in mice during the normal period of programmed cell death. Viral expression of the Pcdh{gamma}c4 isoform rescued transplanted cINs lacking Pcdh{gamma} from cell death. We conclude that Pcdh{gamma}, specifically Pcdh{gamma}c4, plays a critical role in regulating the survival of cINs during their normal period of cell death. This demonstrates a novel specificity in the role of Pcdh{gamma} isoforms in cortical development.

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bioRxiv2022

Production of brain-derived neurotrophic factor gates plasticity in developing visual cortex

We have previously shown that recovery of visual responses to a deprived eye during the critical period in mouse primary visual cortex (V1) requires both export of mRNA encoding brain derived neurotrophic factor (BDNF) to the dendrites of cortical cells (Kaneko et al., 2012) and phosphorylation of the TrkB receptor for BDNF (Kaneko et al., 2008a). TrkB phosphorylation is not required for the loss of response during monocular deprivation (MD). Studies in vitro show that formation of new connections requires BDNF (Meyer-Franke et al., 1995, 1998; Gottmann et al., 2009). We have now studied the temporal relationship between the production of mature BDNF and the recovery of visual responses. Visual cortical responses to an eye whose vision has been occluded for several days during the critical period and is then re-opened recovers rapidly during binocular vision or more slowly following reverse occlusion, when the previously intact fellow eye is occluded in a model of "patch therapy" for amblyopia. The time to recovery of visual responses differed by 18 hours between these two procedures, but in each the production of mature BDNF preceded the recovery by 6 hours. These findings suggest that a spurt of BDNF secretion stimulates the growth of connections serving the deprived eye to restore visual responses. Significance StatementBy demonstrating that BDNF production precedes rather than merely accompanies the increase in cortical responses, we provide further evidence that BDNF production plays a causal role, thereby gating the plasticity that underlies the recovery of visual cortex from monocular deprivation.

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bioRxiv2022

Spatiotemporal recruitment of inhibition and excitation in the mammalian cortex during electrical stimulation

Electrical stimulation has emerged as a powerful and precise treatment in which to modulate aberrant neural activity patterns common in neural dysfunction and disease; however, the physiological process involved in microstimulation is poorly understood, particularly regarding the contributions of inhibitory neurons to shaping stimulation-evoked activity. To address this issue, we used 2-photon imaging of transgenic mice to measure the widespread responses of inhibitory and excitatory neurons to electrical stimulation through a chronically-implanted cortical microelectrode. We found that increasing stimulation amplitude both raised the fraction of neurons that responded to a stimulus and increased the distance at which inhibitory and excitatory neurons were significantly modulated by stimulation; however, the lateral spread of inhibitory activity preceded that of excitatory activity. By 50 {micro}A, a significantly larger fraction of inhibitory neurons vs. excitatory neurons were modulated by stimulation. Increasing amplitude also shifted the temporal response properties of the population -- towards longer-latency excitation close to the electrode tip and strong inhibition of more distant neurons. Animal behavior, specifically their locomotion patterns, strongly correlated with trial-to-trial variability in stimulation-evoked responses. We conclude that changing electrical stimulation amplitude can shift the balance of excitation to inhibition in the brain in a manner that interact with ongoing animal behavior.

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bioRxiv2022

Aberrant cortical spine dynamics after concussive injury are reversed by integrated stress response inhibition.

Traumatic brain injury (TBI) is a leading cause of long-term neurological disability in the world and the strongest environmental risk factor for the development of dementia. Even mild TBI (resulting from concussive injuries) is associated with a >2-fold increase in the risk of dementia onset. Little is known about the cellular mechanisms responsible for the progression of long lasting cognitive deficits. The integrated stress response (ISR), a phylogenetically conserved pathway involved in the cellular response to stress, is activated after TBI, axsnd inhibition of the ISR -- even weeks after injury -- can reverse behavioral and cognitive deficits. However, the cellular mechanisms by which ISR inhibition restores cognition are unknown. Here we used longitudinal two-photon imaging in vivo after concussive injury in mice to study dendritic spine dynamics in the parietal cortex, a brain region involved in working memory. Concussive injury profoundly altered spine dynamics measured up to a month after injury. Strikingly, brief pharmacological treatment with the drug-like small-molecule ISR inhibitor ISRIB entirely reversed the structural changes measured in the parietal cortex and the associated working memory deficits. Thus, both neural and cognitive consequences of concussive injury are mediated in part by activation of the ISR and can be corrected by its inhibition. These findings suggest that targeting ISR activation could serve as a promising approach for the clinical treatment of chronic cognitive deficits after TBI. Significance StatementAfter traumatic brain injury, temporary pharmacological inhibition of the integrated stress response (ISR), with a small-molecule inhibitor (ISRIB), rescued long lasting trauma-induced cognitive deficits. Here, we found that ISRIB treatment rapidly and persistently reversed the aberrant changes in cortical spine dynamics in the parietal cortex while rescuing working memory deficits. These data suggests that the link between the ISR and memory function involves, at least in part, changes in neuronal structure. Targeting ISR activation could serve as a promising approach for the clinical treatment of chronic cognitive deficits after brain injuries.

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bioRxiv2020

Somatostatin-positive neurons in the reticular thalamus modulate gamma rhythms and visual information in mouse V1

Visual perception in natural environments depends on the ability to focus on salient stimuli while ignoring distractions. This kind of selective visual attention is associated with gamma activity in the visual cortex. While the nucleus reticularis thalami (nRT) has been implicated in selective attention, its role in modulating visual perception remains unknown. Here we show that somatostatin-(SOM) but not parvalbumin-expressing (PV) neurons in the nRT preferentially project to visual thalamic nuclei. In freely behaving mice, single-unit and field recordings reveal powerful modulation of both visual information transmission and gamma activity in primary visual cortex (V1), as well as in the dorsal lateral geniculate nucleus (dLGN). These findings pinpoint the SOM neurons in nRT as powerful modulators of the visual information encoding accuracy in V1, and represent a novel circuit through which the nRT can influence representation of visual information.

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bioRxiv2020

Clustered γ-Protocadherins Regulate Cortical Interneuron Programmed Cell Death.

Cortical function critically depends on inhibitory/excitatory balance. GABAergic cortical inhibitory interneurons (cINs) are born in the ventral forebrain. After completing their migration into cortex, their final numbers are adjusted-during a period of postnatal development - by programmed cell death (PCD). The mechanisms that regulate cIN elimination remain controversial. Here we show that genes in the protocadherin (Pcdh)-{gamma} gene cluster, but not in the Pcdh- or Pcdh-{beta} clusters, are required for survival of cINs through a BAX-dependent mechanism. Surprisingly, the physiological and morphological properties of Pcdh-{gamma} deficient and wild type cINs during PCD were indistinguishable. Co-transplantation of wild type and Pcdh-{gamma} deficient interneuron precursor cells demonstrate that: 1) the number of mutant cINs eliminated was much higher than that of wild type cells, but the proportion of mutant or WT cells undergoing cell death was not affected by their density; 2) the presence of mutant cINs increases cell death among wild-type counterparts, and 3) cIN survival is dependent on the expression of Pcdh-{gamma} C3, C4, and C5. We conclude that Pcdh-{gamma}, and specifically {gamma}C3, {gamma}C4, and {gamma}C5, play a critical role in regulating cIN survival during the endogenous period of PCD. SignificanceGABAergic cortical inhibitory interneurons (cINs) in the cerebral cortex originate from the ventral embryonic forebrain. After a long migration, they come together with local excitatory neurons to form cortical circuits. These circuits are responsible for higher brain functions, and the improper balance of excitation/inhibition in the cortex can result in mental diseases. Therefore, an understanding of how the final number of cINs is determined is both biologically and, likely, therapeutically significant. Here we show that cell surface homophilic binding proteins belonging to the clustered protocadherin gene family, specifically three isoforms in the Pcdh-{gamma} cluster, play a key role in the regulation cIN programmed cell death. Co-transplantation of mutant and wild-type cINs shows that Pcdh-{gamma} genes have cell-autonomous and non-cell autonomous roles in the regulation of cIN cell death. This work will help identify the molecular mechanisms and cell-cell interactions that determine how the proper ratio of excitatory to inhibitory neurons is determined in the cerebral cortex.

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bioRxiv2019

Experience-dependent structural plasticity at pre- and postsynaptic sites of layer 2/3 cells in developing visual cortex

The developing brain can respond quickly to altered sensory experience by circuit reorganization. During a critical period in early life, neurons in the primary visual cortex rapidly lose responsiveness to an occluded eye and come to respond better to the open eye. While physiological and some of the molecular mechanisms of this process have been characterized, its structural basis, except for the well-known changes in the thalamocortical projection, remains obscure. To elucidate the relationship between synaptic remodeling and functional changes during this experience-dependent process, we used 2-photon microscopy to image synaptic structures of sparsely labeled layer 2/3 neurons in the binocular zone of mouse primary visual cortex. Anatomical changes at presynaptic and postsynaptic sites in mice undergoing monocular visual deprivation (MD) were compared to those in control mice with normal visual experience. We found that postsynaptic spines remodeled quickly in response to MD, with neurons more strongly dominated by the deprived eye losing more spines. These postsynaptic changes parallel changes in visual responses during MD and their recovery after restoration of binocular vision. In control animals with normal visual experience, the formation of presynaptic boutons increased during the critical period and then declined. MD affected bouton formation, but with a delay, blocking it after 3 days. These findings reveal intracortical anatomical changes in cellular layers of the cortex that can account for rapid activity-dependent plasticity.\n\nSignificance statementThe operation of the cortex depends on the connections among its neurons. Taking advantage of molecular and genetic tools to label major proteins of the presynaptic and postsynaptic densities, we studied how connections of layer 2/3 excitatory neurons in mouse visual cortex were changed by monocular visual deprivation during the critical period, which causes amblyopia. The deprivation induced rapid remodeling of postsynaptic spines and impaired bouton formation. Structural measurement followed by calcium imaging demonstrated a strong correlation between changes in postsynaptic structures and functional responses in individual neurons after monocular deprivation. These findings suggest that anatomical changes at postsynaptic sites serve as a substrate for experience-dependent plasticity in the developing visual cortex.

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bioRxiv2018

Flow stimuli reveal ecologically-appropriate responses in mouse visual cortex

Assessments of the mouse visual system based on spatial frequency analysis imply that its visual capacity is low, with few neurons responding to spatial frequencies greater than 0.5 cycles/degree. However, visually-mediated behaviors, such as prey capture, suggest that the mouse visual system is more precise. We introduce a new stimulus class--visual flow patterns--that is more like what the mouse would encounter in the natural world than are sine-wave gratings but is more tractable for analysis than are natural images. We used 128-site silicon microelectrodes to measure the simultaneous responses of single neurons in the primary visual cortex (V1) of alert mice. While holding temporal-frequency content fixed, we explored a class of drifting patterns of black or white dots that have energy only at higher spatial frequencies. These flow stimuli evoke strong visually-mediated responses well beyond those predicted by spatial frequency analysis. Flow responses predominate in higher spatial-frequency ranges (0.15-1.6 cycles/degree); many are orientation- or direction-selective; and flow responses of many neurons depend strongly on sign of contrast. Many cells exhibit distributed responses across our stimulus ensemble. Together, these results challenge conventional linear approaches to visual processing and expand our understanding of the mouses visual capacity to behaviorally-relevant ranges.\n\nSignificance StatementThe visual system of the mouse is now widely studied as a model for development and disease in humans. Studies of its primary visual cortex (V1) using conventional grating stimuli to construct linear-nonlinear receptive fields suggest that the mouse must have very poor vision. Using novel stimuli resembling the flow of images across the retina as the mouse moves through the grass, we find that most V1 neurons respond reliably to very much finer details of the visual scene than previously believed. Our findings suggest that the conventional notion of a unique receptive field does not capture the operation of the neural network in mouse V1.

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bioRxiv2017

Locomotion induces stimulus-specific response enhancementin adult visual cortex

The responses of neurons in the visual cortex (V1) of adult mammals have long been thought to be stable over long periods. Here, we investigated whether repeated exposure to specific stimuli would enhance V1 visual responses in mice using intrinsic signal imaging through the intact skull and two-photon imaging of calcium signals in single neurons. Mice ran on Styrofoam balls floating on air while viewing one of three different, high-contrast visual stimuli. V1 responses to the stimuli that were viewed by the animal were specifically enhanced, while responses to other stimuli were unaffected. Similar exposure in stationary mice, or in mice in which NMDA receptors were partially blocked, did not significantly enhance responses. These findings indicate that stimulus-specific plasticity in the adult visual cortex depends on concurrent locomotion, presumably as a result of the high-gain state of visual cortex induced by locomotion.\n\nSignificance StatementWe report a rapid and persistent increase in visual cortical responses to visual stimuli presented during locomotion in intact mice. We first used a method that is completely non-invasive, intrinsic signal imaging through the intact skull. We then measured the same effects on single neurons using 2-photon calcium imaging and found that the increase in response to a particular stimulus produced by locomotion depends on how well the neuron is initially driven by the stimulus. To our knowledge, this is the first time such enhancement has been described in single neurons or using non-invasive measurements.

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bioRxiv2017

Locomotion enhances neural encoding of visual stimuli in mouse V1

Neurons in mouse primary visual cortex (V1) are selective for particular properties of visual stimuli. Locomotion causes a change in cortical state that leaves their selectivity unchanged but strengthens their responses. Both locomotion and the change in cortical state are initiated by projections from the mesencephalic locomotor region (MLR), the latter through a disinhibitory circuit in V1. The function served by this change in cortical state is unknown. By recording simultaneously from a large number of single neurons in alert mice viewing moving gratings, we investigated the relationship between locomotion and the information contained within the neural population. We found that locomotion improved encoding of visual stimuli in V1 by two mechanisms. First, locomotion-induced increases in firing rates enhanced the mutual information between visual stimuli and single neuron responses over a fixed window of time. Second, stimulus discriminability was improved, even for fixed population firing rates, because of a decrease in noise correlations across the population during locomotion. These two mechanisms contributed differently to improvements in discriminability across cortical layers, with changes in firing rates most important in the upper layers and changes in noise correlations most important in layer V. Together, these changes resulted in a three- to five-fold reduction in the time needed to precisely encode grating direction and orientation. These results support the hypothesis that cortical state shifts during locomotion to accommodate an increased load on the visual system when mice are moving.\n\nSignificance StatementThis paper contains three novel findings about the representation of information in neurons within the primary visual cortex of the mouse. First, we show that locomotion reduces by at least a factor of three the time needed for information to accumulate in the visual cortex that allows the distinction of different visual stimuli. Second, we show that the effect of locomotion is to increase information in cells of all layers of the visual cortex. Third we show that the means by which information is enhanced by locomotion differs between the upper layers, where the major effect is the increasing of firing rates, and in layer V, where the major effect is the reduction in noise correlations.

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