Browsing by Subject "Visual Cortex"
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Item Open Access A Refined Neuronal Population Measure of Visual Attention.(PloS one, 2015-01) Mayo, J Patrick; Cohen, Marlene R; Maunsell, John HRNeurophysiological studies of cognitive mechanisms such as visual attention typically ignore trial-by-trial variability and instead report mean differences averaged across many trials. Advances in electrophysiology allow for the simultaneous recording of small populations of neurons, which may obviate the need for averaging activity over trials. We recently introduced a method called the attention axis that uses multi-electrode recordings to provide estimates of attentional state of behaving monkeys on individual trials. Here, we refine this method to eliminate problems that can cause bias in estimates of attentional state in certain scenarios. We demonstrate the sources of these problems using simulations and propose an amendment to the previous formulation that provides superior performance in trial-by-trial assessments of attentional state.Item Open Access Advances in color science: from retina to behavior.(The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010-11) Conway, Bevil R; Chatterjee, Soumya; Field, Greg D; Horwitz, Gregory D; Johnson, Elizabeth N; Koida, Kowa; Mancuso, KatherineColor has become a premier model system for understanding how information is processed by neural circuits, and for investigating the relationships among genes, neural circuits, and perception. Both the physical stimulus for color and the perceptual output experienced as color are quite well characterized, but the neural mechanisms that underlie the transformation from stimulus to perception are incompletely understood. The past several years have seen important scientific and technical advances that are changing our understanding of these mechanisms. Here, and in the accompanying minisymposium, we review the latest findings and hypotheses regarding color computations in the retina, primary visual cortex, and higher-order visual areas, focusing on non-human primates, a model of human color vision.Item Open Access Changes in Brain Resting-state Functional Connectivity Associated with Peripheral Nerve Block: A Pilot Study.(Anesthesiology, 2016-08) Melton, M Stephen; Browndyke, Jeffrey N; Harshbarger, Todd B; Madden, David J; Nielsen, Karen C; Klein, Stephen MBACKGROUND: Limited information exists on the effects of temporary functional deafferentation (TFD) on brain activity after peripheral nerve block (PNB) in healthy humans. Increasingly, resting-state functional connectivity (RSFC) is being used to study brain activity and organization. The purpose of this study was to test the hypothesis that TFD through PNB will influence changes in RSFC plasticity in central sensorimotor functional brain networks in healthy human participants. METHODS: The authors achieved TFD using a supraclavicular PNB model with 10 healthy human participants undergoing functional connectivity magnetic resonance imaging before PNB, during active PNB, and during PNB recovery. RSFC differences among study conditions were determined by multiple-comparison-corrected (false discovery rate-corrected P value less than 0.05) random-effects, between-condition, and seed-to-voxel analyses using the left and right manual motor regions. RESULTS: The results of this pilot study demonstrated disruption of interhemispheric left-to-right manual motor region RSFC (e.g., mean Fisher-transformed z [effect size] at pre-PNB 1.05 vs. 0.55 during PNB) but preservation of intrahemispheric RSFC of these regions during PNB. Additionally, there was increased RSFC between the left motor region of interest (PNB-affected area) and bilateral higher order visual cortex regions after clinical PNB resolution (e.g., Fisher z between left motor region of interest and right and left lingual gyrus regions during PNB, -0.1 and -0.6 vs. 0.22 and 0.18 after PNB resolution, respectively). CONCLUSIONS: This pilot study provides evidence that PNB has features consistent with other models of deafferentation, making it a potentially useful approach to investigate brain plasticity. The findings provide insight into RSFC of sensorimotor functional brain networks during PNB and PNB recovery and support modulation of the sensory-motor integration feedback loop as a mechanism for explaining the behavioral correlates of peripherally induced TFD through PNB.Item Open Access Configural specificity of the lateral occipital cortex.(Neuropsychologia, 2010-09) Appelbaum, LG; Ales, JM; Cottereau, B; Norcia, AMWhile regions of the lateral occipital cortex (LOC) are known to be selective for objects relative to feature-matched controls, it is not known what set of cues or configurations are used to promote this selectivity. Many theories of perceptual organization have emphasized the figure-ground relationship as being especially important in object-level processing. In the present work we studied the role of perceptual organization in eliciting visual evoked potentials from the object selective LOC. To do this, we used two-region stimuli in which the regions were modulated at different temporal frequencies and were comprised of either symmetric or asymmetric arrangements. The asymmetric arrangement produced an unambiguous figure-ground relationship consistent with a smaller figure region surrounded by a larger background, while four different symmetric arrangements resulted in ambiguous figure-ground relationships but still possessed strong kinetic boundaries between the regions. The surrounded figure-ground arrangement evoked greater activity in the LOC relative to first-tier visual areas (V1-V3). Response selectivity in the LOC, however, was not present for the four different types of symmetric stimuli. These results suggest that kinetic texture boundaries alone are not sufficient to trigger selective processing in the LOC, but that the spatial configuration of a figure that is surrounded by a larger background is both necessary and sufficient to selectively activate the LOC.Item Open Access Coordinated multiplexing of information about separate objects in visual cortex.(eLife, 2022-11) Jun, Na Young; Ruff, Douglas A; Kramer, Lily E; Bowes, Brittany; Tokdar, Surya T; Cohen, Marlene R; Groh, Jennifer MSensory receptive fields are large enough that they can contain more than one perceptible stimulus. How, then, can the brain encode information about each of the stimuli that may be present at a given moment? We recently showed that when more than one stimulus is present, single neurons can fluctuate between coding one vs. the other(s) across some time period, suggesting a form of neural multiplexing of different stimuli (Caruso et al., 2018). Here, we investigate (a) whether such coding fluctuations occur in early visual cortical areas; (b) how coding fluctuations are coordinated across the neural population; and (c) how coordinated coding fluctuations depend on the parsing of stimuli into separate vs. fused objects. We found coding fluctuations do occur in macaque V1 but only when the two stimuli form separate objects. Such separate objects evoked a novel pattern of V1 spike count ('noise') correlations involving distinct distributions of positive and negative values. This bimodal correlation pattern was most pronounced among pairs of neurons showing the strongest evidence for coding fluctuations or multiplexing. Whether a given pair of neurons exhibited positive or negative correlations depended on whether the two neurons both responded better to the same object or had different object preferences. Distinct distributions of spike count correlations based on stimulus preferences were also seen in V4 for separate objects but not when two stimuli fused to form one object. These findings suggest multiple objects evoke different response dynamics than those evoked by single stimuli, lending support to the multiplexing hypothesis and suggesting a means by which information about multiple objects can be preserved despite the apparent coarseness of sensory coding.Item Open Access Cortical dynamics during naturalistic sensory stimulations: experiments and models.(Journal of physiology, Paris, 2011-01) Mazzoni, Alberto; Brunel, Nicolas; Cavallari, Stefano; Logothetis, Nikos K; Panzeri, StefanoWe report the results of our experimental and theoretical investigations of the neural response dynamics in primary visual cortex (V1) during naturalistic visual stimulation. We recorded Local Field Potentials (LFPs) and spiking activity from V1 of anaesthetized macaques during binocular presentation of Hollywood color movies. We analyzed these recordings with information theoretic methods, and found that visual information was encoded mainly by two bands of LFP responses: the network fluctuations measured by the phase and power of low-frequency (less than 12 Hz) LFPs; and fast gamma-range (50-100 Hz) oscillations. Both the power and phase of low frequency LFPs carried information largely complementary to that carried by spikes, whereas gamma range oscillations carried information largely redundant to that of spikes. To interpret these results within a quantitative theoretical framework, we then simulated a sparsely connected recurrent network of excitatory and inhibitory neurons receiving slowly varying naturalistic inputs, and we determined how the LFPs generated by the network encoded information about the inputs. We found that this simulated recurrent network reproduced well the experimentally observed dependency of LFP information upon frequency. This network encoded the overall strength of the input into the power of gamma-range oscillations generated by inhibitory-excitatory neural interactions, and encoded slow variations in the input by entraining the network LFP at the corresponding frequency. This dynamical behavior accounted quantitatively for the independent information carried by high and low frequency LFPs, and for the experimentally observed cross-frequency coupling between phase of slow LFPs and the power of gamma LFPs. We also present new results showing that the model's dynamics also accounted for the extra visual information that the low-frequency LFP phase of spike firing carries beyond that carried by spike rates. Overall, our results suggest biological mechanisms by which cortex can multiplex information about naturalistic sensory environments.Item Open Access Division of labor in frontal eye field neurons during presaccadic remapping of visual receptive fields.(J Neurophysiol, 2012-10) Shin, Sooyoon; Sommer, Marc AOur percept of visual stability across saccadic eye movements may be mediated by presaccadic remapping. Just before a saccade, neurons that remap become visually responsive at a future field (FF), which anticipates the saccade vector. Hence, the neurons use corollary discharge of saccades. Many of the neurons also decrease their response at the receptive field (RF). Presaccadic remapping occurs in several brain areas including the frontal eye field (FEF), which receives corollary discharge of saccades in its layer IV from a collicular-thalamic pathway. We studied, at two levels, the microcircuitry of remapping in the FEF. At the laminar level, we compared remapping between layers IV and V. At the cellular level, we compared remapping between different neuron types of layer IV. In the FEF in four monkeys (Macaca mulatta), we identified 27 layer IV neurons with orthodromic stimulation and 57 layer V neurons with antidromic stimulation from the superior colliculus. With the use of established criteria, we classified the layer IV neurons as putative excitatory (n = 11), putative inhibitory (n = 12), or ambiguous (n = 4). We found that just before a saccade, putative excitatory neurons increased their visual response at the RF, putative inhibitory neurons showed no change, and ambiguous neurons increased their visual response at the FF. None of the neurons showed presaccadic visual changes at both RF and FF. In contrast, neurons in layer V showed full remapping (at both the RF and FF). Our data suggest that elemental signals for remapping are distributed across neuron types in early cortical processing and combined in later stages of cortical microcircuitry.Item Open Access Feature-specific clusters of neurons and decision-related neuronal activity.(The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014-06) Mayo, J Patrick; Verhoef, Bram-ErnstItem Open Access Graded Neuronal Modulations Related to Visual Spatial Attention.(The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016-05) Mayo, J Patrick; Maunsell, John HRUNLABELLED:Studies of visual attention in monkeys typically measure neuronal activity when the stimulus event to be detected occurs at a cued location versus when it occurs at an uncued location. But this approach does not address how neuronal activity changes relative to conditions where attention is unconstrained by cueing. Human psychophysical studies have used neutral cueing conditions and found that neutrally cued behavioral performance is generally intermediate to that of cued and uncued conditions (Posner et al., 1978; Mangun and Hillyard, 1990; Montagna et al., 2009). To determine whether the neuronal correlates of visual attention during neutral cueing are similarly intermediate, we trained macaque monkeys to detect changes in stimulus orientation that were more likely to occur at one location (cued) than another (uncued), or were equally likely to occur at either stimulus location (neutral). Consistent with human studies, performance was best when the location was cued, intermediate when both locations were neutrally cued, and worst when the location was uncued. Neuronal modulations in visual area V4 were also graded as a function of cue validity and behavioral performance. By recording from both hemispheres simultaneously, we investigated the possibility of switching attention between stimulus locations during neutral cueing. The results failed to support a unitary "spotlight" of attention. Overall, our findings indicate that attention-related changes in V4 are graded to accommodate task demands. SIGNIFICANCE STATEMENT:Studies of the neuronal correlates of attention in monkeys typically use visual cues to manipulate where attention is focused ("cued" vs "uncued"). Human psychophysical studies often also include neutrally cued trials to study how attention naturally varies between points of interest. But the neuronal correlates of this neutral condition are unclear. We measured behavioral performance and neuronal activity in cued, uncued, and neutrally cued blocks of trials. Behavioral performance and neuronal responses during neutral cueing were intermediate to those of the cued and uncued conditions. We found no signatures of a single mechanism of attention that switches between stimulus locations. Thus, attention-related changes in neuronal activity are largely hemisphere-specific and graded according to task demands.Item Open Access Imagery and retrieval of auditory and visual information: neural correlates of successful and unsuccessful performance.(Neuropsychologia, 2011-06) Huijbers, Willem; Pennartz, Cyriel MA; Rubin, David C; Daselaar, Sander MRemembering past events - or episodic retrieval - consists of several components. There is evidence that mental imagery plays an important role in retrieval and that the brain regions supporting imagery overlap with those supporting retrieval. An open issue is to what extent these regions support successful vs. unsuccessful imagery and retrieval processes. Previous studies that examined regional overlap between imagery and retrieval used uncontrolled memory conditions, such as autobiographical memory tasks, that cannot distinguish between successful and unsuccessful retrieval. A second issue is that fMRI studies that compared imagery and retrieval have used modality-aspecific cues that are likely to activate auditory and visual processing regions simultaneously. Thus, it is not clear to what extent identified brain regions support modality-specific or modality-independent imagery and retrieval processes. In the current fMRI study, we addressed this issue by comparing imagery to retrieval under controlled memory conditions in both auditory and visual modalities. We also obtained subjective measures of imagery quality allowing us to dissociate regions contributing to successful vs. unsuccessful imagery. Results indicated that auditory and visual regions contribute both to imagery and retrieval in a modality-specific fashion. In addition, we identified four sets of brain regions with distinct patterns of activity that contributed to imagery and retrieval in a modality-independent fashion. The first set of regions, including hippocampus, posterior cingulate cortex, medial prefrontal cortex and angular gyrus, showed a pattern common to imagery/retrieval and consistent with successful performance regardless of task. The second set of regions, including dorsal precuneus, anterior cingulate and dorsolateral prefrontal cortex, also showed a pattern common to imagery and retrieval, but consistent with unsuccessful performance during both tasks. Third, left ventrolateral prefrontal cortex showed an interaction between task and performance and was associated with successful imagery but unsuccessful retrieval. Finally, the fourth set of regions, including ventral precuneus, midcingulate cortex and supramarginal gyrus, showed the opposite interaction, supporting unsuccessful imagery, but successful retrieval performance. Results are discussed in relation to reconstructive, attentional, semantic memory, and working memory processes. This is the first study to separate the neural correlates of successful and unsuccessful performance for both imagery and retrieval and for both auditory and visual modalities.Item Open Access Inhibition stabilization is a widespread property of cortical networks.(eLife, 2020-06-29) Sanzeni, Alessandro; Akitake, Bradley; Goldbach, Hannah C; Leedy, Caitlin E; Brunel, Nicolas; Histed, Mark HMany cortical network models use recurrent coupling strong enough to require inhibition for stabilization. Yet it has been experimentally unclear whether inhibition-stabilized network (ISN) models describe cortical function well across areas and states. Here, we test several ISN predictions, including the counterintuitive (paradoxical) suppression of inhibitory firing in response to optogenetic inhibitory stimulation. We find clear evidence for ISN operation in mouse visual, somatosensory, and motor cortex. Simple two-population ISN models describe the data well and let us quantify coupling strength. Although some models predict a non-ISN to ISN transition with increasingly strong sensory stimuli, we find ISN effects without sensory stimulation and even during light anesthesia. Additionally, average paradoxical effects result only with transgenic, not viral, opsin expression in parvalbumin (PV)-positive neurons; theory and expression data show this is consistent with ISN operation. Taken together, these results show strong coupling and inhibition stabilization are common features of the cortex.Item Open Access Neuronal Adaptation: Tired Neurons or Wired Networks?(Trends in neurosciences, 2017-03) Mayo, J Patrick; Smith, Matthew ANeuronal adaptation - time-dependent modulation of sensory responses following sequential stimuli - is thought to be a consequence of synaptic plasticity. But recent, empirically-grounded, modeling by Quiroga and colleagues demonstrates that the adaptation of visual cortical responses can be described by recurrent network connections with fixed synaptic weights.Item Open Access Spatial and temporal scales of neuronal correlation in visual area V4.(J Neurosci, 2013-03-20) Smith, Matthew A; Sommer, Marc AThe spiking activity of nearby cortical neurons is correlated on both short and long time scales. Understanding this shared variability in firing patterns is critical for appreciating the representation of sensory stimuli in ensembles of neurons, the coincident influences of neurons on common targets, and the functional implications of microcircuitry. Our knowledge about neuronal correlations, however, derives largely from experiments that used different recording methods, analysis techniques, and cortical regions. Here we studied the structure of neuronal correlation in area V4 of alert macaques using recording and analysis procedures designed to match those used previously in primary visual cortex (V1), the major input to V4. We found that the spatial and temporal properties of correlations in V4 were remarkably similar to those of V1, with two notable differences: correlated variability in V4 was approximately one-third the magnitude of that in V1 and synchrony in V4 was less temporally precise than in V1. In both areas, spontaneous activity (measured during fixation while viewing a blank screen) was approximately twice as correlated as visual-evoked activity. The results provide a foundation for understanding how the structure of neuronal correlation differs among brain regions and stages in cortical processing and suggest that it is likely governed by features of neuronal circuits that are shared across the visual cortex.Item Open Access Stimulus dependence of local field potential spectra: experiment versus theory.(The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014-10) Barbieri, Francesca; Mazzoni, Alberto; Logothetis, Nikos K; Panzeri, Stefano; Brunel, NicolasThe local field potential (LFP) captures different neural processes, including integrative synaptic dynamics that cannot be observed by measuring only the spiking activity of small populations. Therefore, investigating how LFP power is modulated by external stimuli can offer important insights into sensory neural representations. However, gaining such insight requires developing data-driven computational models that can identify and disambiguate the neural contributions to the LFP. Here, we investigated how networks of excitatory and inhibitory integrate-and-fire neurons responding to time-dependent inputs can be used to interpret sensory modulations of LFP spectra. We computed analytically from such models the LFP spectra and the information that they convey about input and used these analytical expressions to fit the model to LFPs recorded in V1 of anesthetized macaques (Macaca mulatta) during the presentation of color movies. Our expressions explain 60%-98% of the variance of the LFP spectrum shape and its dependency upon movie scenes and we achieved this with realistic values for the best-fit parameters. In particular, synaptic best-fit parameters were compatible with experimental measurements and the predictions of firing rates, based only on the fit of LFP data, correlated with the multiunit spike rate recorded from the same location. Moreover, the parameters characterizing the input to the network across different movie scenes correlated with cross-scene changes of several image features. Our findings suggest that analytical descriptions of spiking neuron networks may become a crucial tool for the interpretation of field recordings.Item Open Access The time course of segmentation and cue-selectivity in the human visual cortex.(PLoS One, 2012) Appelbaum, Lawrence G; Ales, Justin M; Norcia, Anthony MTexture discontinuities are a fundamental cue by which the visual system segments objects from their background. The neural mechanisms supporting texture-based segmentation are therefore critical to visual perception and cognition. In the present experiment we employ an EEG source-imaging approach in order to study the time course of texture-based segmentation in the human brain. Visual Evoked Potentials were recorded to four types of stimuli in which periodic temporal modulation of a central 3° figure region could either support figure-ground segmentation, or have identical local texture modulations but not produce changes in global image segmentation. The image discontinuities were defined either by orientation or phase differences across image regions. Evoked responses to these four stimuli were analyzed both at the scalp and on the cortical surface in retinotopic and functional regions-of-interest (ROIs) defined separately using fMRI on a subject-by-subject basis. Texture segmentation (tsVEP: segmenting versus non-segmenting) and cue-specific (csVEP: orientation versus phase) responses exhibited distinctive patterns of activity. Alternations between uniform and segmented images produced highly asymmetric responses that were larger after transitions from the uniform to the segmented state. Texture modulations that signaled the appearance of a figure evoked a pattern of increased activity starting at ∼143 ms that was larger in V1 and LOC ROIs, relative to identical modulations that didn't signal figure-ground segmentation. This segmentation-related activity occurred after an initial response phase that did not depend on the global segmentation structure of the image. The two cue types evoked similar tsVEPs up to 230 ms when they differed in the V4 and LOC ROIs. The evolution of the response proceeded largely in the feed-forward direction, with only weak evidence for feedback-related activity.Item Open Access The time course of shape discrimination in the human brain.(Neuroimage, 2013-02-15) Ales, Justin M; Appelbaum, L Gregory; Cottereau, Benoit R; Norcia, Anthony MThe lateral occipital cortex (LOC) activates selectively to images of intact objects versus scrambled controls, is selective for the figure-ground relationship of a scene, and exhibits at least some degree of invariance for size and position. Because of these attributes, it is considered to be a crucial part of the object recognition pathway. Here we show that human LOC is critically involved in perceptual decisions about object shape. High-density EEG was recorded while subjects performed a threshold-level shape discrimination task on texture-defined figures segmented by either phase or orientation cues. The appearance or disappearance of a figure region from a uniform background generated robust visual evoked potentials throughout retinotopic cortex as determined by inverse modeling of the scalp voltage distribution. Contrasting responses from trials containing shape changes that were correctly detected (hits) with trials in which no change occurred (correct rejects) revealed stimulus-locked, target-selective activity in the occipital visual areas LOC and V4 preceding the subject's response. Activity that was locked to the subjects' reaction time was present in the LOC. Response-locked activity in the LOC was determined to be related to shape discrimination for several reasons: shape-selective responses were silenced when subjects viewed identical stimuli but their attention was directed away from the shapes to a demanding letter discrimination task; shape-selectivity was present across four different stimulus configurations used to define the figure; LOC responses correlated with participants' reaction times. These results indicate that decision-related activity is present in the LOC when subjects are engaged in threshold-level shape discriminations.Item Open Access Understanding the relationships between spike rate and delta/gamma frequency bands of LFPs and EEGs using a local cortical network model.(NeuroImage, 2010-09) Mazzoni, Alberto; Whittingstall, Kevin; Brunel, Nicolas; Logothetis, Nikos K; Panzeri, StefanoDespite the widespread use of EEGs to measure the large-scale dynamics of the human brain, little is known on how the dynamics of EEGs relates to that of the underlying spike rates of cortical neurons. However, progress was made by recent neurophysiological experiments reporting that EEG delta-band phase and gamma-band amplitude reliably predict some complementary aspects of the time course of spikes of visual cortical neurons. To elucidate the mechanisms behind these findings, here we hypothesize that the EEG delta phase reflects shifts of local cortical excitability arising from slow fluctuations in the network input due to entrainment to sensory stimuli or to fluctuations in ongoing activity, and that the resulting local excitability fluctuations modulate both the spike rate and the engagement of excitatory-inhibitory loops producing gamma-band oscillations. We quantitatively tested these hypotheses by simulating a recurrent network of excitatory and inhibitory neurons stimulated with dynamic inputs presenting temporal regularities similar to that of thalamic responses during naturalistic visual stimulation and during spontaneous activity. The network model reproduced in detail the experimental relationships between spike rate and EEGs, and suggested that the complementariness of the prediction of spike rates obtained from EEG delta phase or gamma amplitude arises from nonlinearities in the engagement of excitatory-inhibitory loops and from temporal modulations in the amplitude of the network input, which respectively limit the predictability of spike rates from gamma amplitude or delta phase alone. The model suggested also ways to improve and extend current algorithms for online prediction of spike rates from EEGs.Item Open Access Unmasking Proteolytic Activity for Adult Visual Cortex Plasticity by the Removal of Lynx1.(The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015-09) Bukhari, Noreen; Burman, Poromendro N; Hussein, Ayan; Demars, Michael P; Sadahiro, Masato; Brady, Daniel M; Tsirka, Stella E; Russo, Scott J; Morishita, HirofumiUnlabelled
Experience-dependent cortical plasticity declines with age. At the molecular level, experience-dependent proteolytic activity of tissue plasminogen activator (tPA) becomes restricted in the adult brain if mice are raised in standard cages. Understanding the mechanism for the loss of permissive proteolytic activity is therefore a key link for improving function in adult brains. Using the mouse primary visual cortex (V1) as a model, we demonstrate that tPA activity in V1 can be unmasked following 4 d of monocular deprivation when the mice older than 2 months are raised in standard cages by the genetic removal of Lynx1, a negative regulator of adult plasticity. This was also associated with the reduction of stubby and thin spine density and enhancement of ocular dominance shift in adult V1 of Lynx1 knock-out (KO) mice. These structural and functional changes were tPA-dependent because genetic removal of tPA in Lynx1 KO mice can block the monocular deprivation-dependent reduction of dendritic spine density, whereas both genetic and adult specific inhibition of tPA activity can ablate the ocular dominance shift in Lynx1 KO mice. Our work demonstrates that the adult brain has an intrinsic potential for experience-dependent elevation of proteolytic activity to express juvenile-like structural and functional changes but is effectively limited by Lynx1 if mice are raised in standard cages. Insights into the Lynx1-tPA plasticity mechanism may provide novel therapeutic targets for adult brain disorders.Significance statement
Experience-dependent proteolytic activity of tissue plasminogen activator (tPA) becomes restricted in the adult brain in correlation with the decline in cortical plasticity when mice are raised in standard cages. We demonstrated that removal of Lynx1, one of negative regulators of plasticity, unmasks experience-dependent tPA elevation in visual cortex of adult mice reared in standard cages. This proteolytic elevation facilitated dendritic spine reduction and ocular dominance plasticity in adult visual cortex. This is the first demonstration of adult brain to retain the intrinsic capacity to elevate tPA in an experience-dependent manner but is effectively limited by Lynx1. tPA-Lynx1 may potentially be a new candidate mechanism for interventions that were shown to activate plasticity in adult brain.