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Mriganka Sur

Publications and source records attributed to Mriganka Sur.

At least 19 recordsLinked to original sources
PubMed2006

In vivo two-photon imaging reveals a role of arc in enhancing orientation specificity in visual cortex.

Cortical representations of visual information are modified by an animal's visual experience. To investigate the mechanisms in mice, we replaced the coding part of the neural activity-regulated immediate early gene Arc with a GFP gene and repeatedly monitored visual experience-induced GFP expression in adult primary visual cortex by in vivo two-photon microscopy. In Arc-positive GFP heterozygous mice, the pattern of GFP-positive cells exhibited orientation specificity. Daily presentations of the same stimulus led to the reactivation of a progressively smaller population with greater reactivation reliability. This adaptation process was not affected by the lack of Arc in GFP homozygous mice. However, the number of GFP-positive cells with low orientation specificity was greater, and the average spike tuning curve was broader in the adult homozygous compared to heterozygous or wild-type mice. These results suggest a physiological function of Arc in enhancing the overall orientation specificity of visual cortical neurons during the post-eye-opening life of an animal.

Animals↗
PubMed2006

Plasticity and specificity of cortical processing networks.

The cerebral cortex is subdivided into discrete functional areas that are defined by specific properties, including the presence of different cell types, molecular expression patterns, microcircuitry and long-range connectivity. These properties enable different areas of cortex to carry out distinct functions. Emerging data argue that the particular structure and identity of cortical areas derives not only from specific inputs but also from unique processing networks. The aim of this review is to summarize current information on the interplay of intrinsic molecular cues with activity patterns that are driven by sensory experience and shape cortical networks as they develop, emphasizing synaptic connections in networks that process vision. This review is part of the TINS special issue on The Neural Substrates of Cognition.

Animals↗
PubMed2006

Gene expression changes and molecular pathways mediating activity-dependent plasticity in visual cortex.

Two key models for examining activity-dependent development of primary visual cortex (V1) involve either reduction of activity in both eyes via dark-rearing (DR) or imbalance of activity between the two eyes via monocular deprivation (MD). Combining DNA microarray analysis with computational approaches, RT-PCR, immunohistochemistry and physiological imaging, we find that DR leads to (i) upregulation of genes subserving synaptic transmission and electrical activity, consistent with a coordinated response of cortical neurons to reduction of visual drive, and (ii) downregulation of parvalbumin expression, implicating parvalbumin-expressing interneurons as underlying the delay in cortical maturation after DR. MD partially activates homeostatic mechanisms but differentially upregulates molecular pathways related to growth factors and neuronal degeneration, consistent with reorganization of connections after MD. Expression of a binding protein of insulin-like growth factor-1 (IGF1) is highly upregulated after MD, and exogenous application of IGF1 prevents the physiological effects of MD on ocular dominance plasticity examined in vivo.

Animals↗
PubMed2006

Remodeling of synaptic structure in sensory cortical areas in vivo.

Although plastic changes are known to occur in developing and adult cortex, it remains unclear whether these changes require remodeling of cortical circuitry whereby synapses are formed and eliminated or whether they rely on changes in the strength of existing synapses. To determine the structural stability of dendritic spines and axon terminals in vivo, we chose two approaches. First, we performed time-lapse two-photon imaging of dendritic spine motility of layer 5 pyramidal neurons in juvenile [postnatal day 28 (P28)] mice in visual, auditory, and somatosensory cortices. We found that there were differences in basal rates of dendritic spine motility of the same neuron type in different cortices, with visual cortex exhibiting the least structural dynamics. Rewiring visual input into the auditory cortex at birth, however, failed to alter dendritic spine motility, suggesting that structural plasticity rates might be intrinsic to the cortical region. Second, we investigated the persistence of both the presynaptic (axon terminals) and postsynaptic (dendritic spine) structures in young adult mice (P40-P61), using chronic in vivo two-photon imaging in different sensory areas. Both terminals and spines were relatively stable, with >80% persisting over a 3 week period in all sensory regions. Axon terminals were more stable than dendritic spines. These data suggest that changes in network function during adult learning and memory might occur through changes in the strength and efficacy of existing synapses as well as some remodeling of connectivity through the loss and gain of synapses.

Animals↗
PubMed2006

Visual activity and cortical rewiring: activity-dependent plasticity of cortical networks.

The mammalian cortex is organized anatomically into discrete areas, which receive, process, and transmit neural signals along functional pathways. These pathways form a system of complex networks that wire up through development and refine their connections into adulthood. Understanding the processes of cortical-pathway formation, maintenance, and experience-dependent plasticity has been among the major goals of contemporary neurobiology. In this chapter, we will discuss an experimental model used to investigate the role of activity in the patterning of cortical networks during development. This model involves the "rewiring" of visual inputs into the auditory thalamus and subsequent remodeling of the auditory cortex to process visual information. We review the molecular, cellular, and physiological mechanisms of visual "rewiring" and activity-dependent shaping of cortical networks.

Animals↗
PubMed2006

Image structure at the center of gaze during free viewing.

It is generally believed that the visual system is adapted to the statistics of the visual world. Measuring and understanding these statistics require precise knowledge of the structure of the signals reaching fovea during image scanning. However, despite the fact that eye movements cause retinal stimulation to change several times in a second, it is implicitly assumed that images are sampled uniformly during natural viewing. By analyzing the eye movements of three rhesus monkeys freely viewing natural scenes, we report here significant anisotropy in stimulus statistics at the center of gaze. We find that fixation on an image patch is more likely to be followed by a saccade to a nearby patch of similar orientation structure or by a saccade to a more distant patch of largely dissimilar orientation structure. Furthermore, we show that orientation-selective neurons in the primary visual cortex (V1) can take advantage of eye movement statistics to selectively improve their discrimination performance.

Action Potentials↗
PubMed2005

Local networks in visual cortex and their influence on neuronal responses and dynamics.

Networks of neurons in the cerebral cortex generate complex outputs that are not simply predicted by their inputs. These emergent responses underlie the function of the cortex. Understanding how cortical networks carry out such transformations requires a description of the responses of individual neurons and of their networks at multiple levels of analysis. We focus on orientation selectivity in primary visual cortex as a model system to understand cortical network computations. Recent experiments in our laboratory and others provide significant insight into how cortical networks generate and maintain orientation selectivity. We first review evidence for the diversity of orientation tuning characteristics in visual cortex. We then describe experiments that combine optical imaging of orientation maps with intracellular and extracellular recordings from individual neurons at known locations in the orientation map. The data indicate that excitatory and inhibitory synaptic inputs are summed across the cortex in a manner that is consistent with simple rules of integration of local inputs. These rules arise from known anatomical projection patterns in visual cortex. We propose that the generation and plasticity of orientation tuning is strongly influenced by local cortical networks-the diversity of these properties arises in part from the diversity of neighbourhood features that derive from the orientation map.

Animals↗
PubMed2005

Patterning and plasticity of the cerebral cortex.

The cerebral cortex of the human brain is a sheet of about 10 billion neurons divided into discrete subdivisions or areas that process particular aspects of sensation, movement, and cognition. Recent evidence has begun to transform our understanding of how cortical areas form, make specific connections with other brain regions, develop unique processing networks, and adapt to changes in inputs.

Animals↗
PubMed2005

Tilt aftereffect and adaptation-induced changes in orientation tuning in visual cortex.

The tilt aftereffect (TAE) is a visual illusion in which prolonged adaptation to an oriented stimulus causes shifts in subsequent perceived orientations. Historically, neural models of the TAE have explained it as the outcome of response suppression of neurons tuned to the adapting orientation. Recent physiological studies of neurons in primary visual cortex (V1) have confirmed that such response suppression exists. However, it was also found that the preferred orientations of neurons shift away from the adapting orientation. Here we show that adding this second factor to a population coding model of V1 improves the correspondence between neurophysiological data and TAE measurements. According to our model, the shifts in preferred orientation have the opposite effect as response suppression, reducing the magnitude of the TAE.

Adaptation, Physiological↗
PubMed2005

Effects of synaptic activity on dendritic spine motility of developing cortical layer v pyramidal neurons.

It is increasingly clear that dendritic spines play an important role in compartmentalizing post-synaptic signals and that their dynamic morphological properties have functional consequences. Here, we examine this issue using two-photon microscopy to characterize spine motility on layer V pyramidal neurons in acute slices of the developing mouse cortex. In this system, all spine classes except filopodia become less dynamic as development proceeds. General manipulations of activity (TTX or KCl treatment) do not alter spine dynamics, although increased glutamatergic transmission (AMPA or NMDA treatment) stabilizes developing cortical spines. These effects on spine dynamics do not appear to be related to AMPA or NMDA receptor expression as assessed with immunolabeling, as there is no correlation between spine motility and AMPA (GluR1/2) or NMDA (NR1/NR2B) receptor subunit expression on a spine by spine basis. These results indicate that activity through glutamatergic synapses is important for regulating spine motility in the developing mouse cortex, and that the relative complement of receptors, while different across morphological classifications, cannot account for differences in dynamic structural changes in dendritic spines.

Actins↗
PubMed2005

Ephrin-A2 and -A5 influence patterning of normal and novel retinal projections to the thalamus: conserved mapping mechanisms in visual and auditory thalamic targets.

Sensory axons are targeted to modality-specific nuclei in the thalamus. Retinal ganglion cell axons project retinotopically to their principal thalamic target, the dorsal lateral geniculate nucleus (LGd), in a pattern likely dictated by the expression of molecular gradients in the LGd. Deafferenting the auditory thalamus induces retinal axons to innervate the medial geniculate nucleus (MGN). These retino-MGN projections also show retinotopic organization. Here we show that ephrin-A2 and -A5, which are expressed in similar gradients in the MGN and LGd, can be used to pattern novel retinal projections in the MGN. As in the LGd, retinal axons from each eye terminate in discrete eye-specific zones in the MGN of rewired wild-type and ephrin-A2/A5 knockout mice. However, ipsilateral eye axons, which arise from retinal regions of high EphA5 receptor expression and represent central visual field, terminate in markedly different ways in the two mice. In rewired wild-type mice, ipsilateral axons specifically avoid areas of high ephrin expression in the MGN. In rewired ephrin knockout mice, ipsilateral projections shift in location and spread more broadly, leading to an expanded representation of the ipsilateral eye in the MGN. Similarly, ipsilateral projections to the LGd in ephrin knockout mice are shifted and are more widespread than in the LGd of wild-type mice. In the MGN, as in the LGd, terminations from the two eyes show little overlap even in the knockout mice, suggesting that local interocular segregation occurs regardless of other patterning determinants. Our data demonstrate that graded topographic labels, such as the ephrins, can serve to shape multiple related aspects of afferent patterning, including topographic mapping and the extent and spread of eye-specific projections. Furthermore, when mapping labels and other cues are expressed in multiple target zones, novel projections are patterned according to rules that operate in their canonical targets.

Animals↗
PubMed2005

The coordinated mapping of visual space and response features in visual cortex.

Whether general principles can explain the layouts of cortical maps remains unresolved. In primary visual cortex of ferret, the relationships between the maps of visual space and response features are predicted by a "dimension-reduction" model. The representation of visual space is anisotropic, with the elevation and azimuth axes having different magnification. This anisotropy is reflected in the orientation, ocular dominance, and spatial frequency domains, which are elongated such that their directions of rapid change, or high-gradient axes, are orthogonal to the high-gradient axis of the visual map. The feature maps are also strongly interdependent-their high-gradient regions avoid one another and intersect orthogonally where essential, so that overlap is minimized. Our results demonstrate a clear influence of the visual map on each feature map. In turn, the local representation of visual space is smooth, as predicted when many features are mapped within a cortical area.

Animals↗
PubMed2005

Invariant computations in local cortical networks with balanced excitation and inhibition.

Cortical computations critically involve local neuronal circuits. The computations are often invariant across a cortical area yet are carried out by networks that can vary widely within an area according to its functional architecture. Here we demonstrate a mechanism by which orientation selectivity is computed invariantly in cat primary visual cortex across an orientation preference map that provides a wide diversity of local circuits. Visually evoked excitatory and inhibitory synaptic conductances are balanced exquisitely in cortical neurons and thus keep the spike response sharply tuned at all map locations. This functional balance derives from spatially isotropic local connectivity of both excitatory and inhibitory cells. Modeling results demonstrate that such covariation is a signature of recurrent rather than purely feed-forward processing and that the observed isotropic local circuit is sufficient to generate invariant spike tuning.

Action Potentials↗
PubMed2005

Fabrication and biocompatibility of polypyrrole implants suitable for neural prosthetics.

Finding a conductive substrate that promotes neural interactions is an essential step for advancing neural interfaces. The biocompatibility and conductive properties of polypyrrole (PPy) make it an attractive substrate for neural scaffolds, electrodes, and devices. Stand-alone polymer implants also provide the additional advantages of flexibility and biodegradability. To examine PPy biocompatibility, dissociated primary cerebral cortical cells were cultured on PPy samples that had been doped with polystyrene-sulfonate (PSS) or sodium dodecylbenzenesulfonate (NaDBS). Various conditions were used for electrodeposition to produce different surface properties. Neural networks grew on all of the PPy surfaces. PPy implants, consisting of the same dopants and conditions, were surgically implanted in the cerebral cortex of the rat. The results were compared to stab wounds and Teflon implants of the same size. Quantification of the intensity and extent of gliosis at 3- and 6-week time points demonstrated that all versions of PPy were at least as biocompatible as Teflon and in fact performed better in most cases. In all of the PPy implant cases, neurons and glial cells enveloped the implant. In several cases, neural tissue was present in the lumen of the implants, allowing contact of the brain parenchyma through the implants.

Animals↗
PubMed2005

Bottom-up and top-down dynamics in visual cortex.

A key emergent property of the primary visual cortex (V1) is the orientation selectivity of its neurons. Recent experiments demonstrate remarkable bottom-up and top-down plasticity in orientation networks of the adult cortex. The basis for such dynamics is the mechanism by which orientation tuning is created and maintained, by integration of thalamocortical and intracortical inputs. Intracellular measurements of excitatory and inhibitory synaptic conductances reveal that excitation and inhibition balance each other at all locations in the cortex. This balance is particularly critical at pinwheel centers of the orientation map, where neurons receive intracortical input from a wide diversity of local orientations. The orientation tuning of neurons in adult V1 changes systematically after short-term exposure to one stimulus orientation. Such reversible physiological shifts in tuning parallel the orientation tilt aftereffect observed psychophysically. Neurons at or near pinwheel centers show pronounced changes in orientation preference after adaptation with an oriented stimulus, while neurons in iso-orientation domains show minimal changes. Neurons in V1 of alert, behaving monkeys also exhibit short-term orientation plasticity after very brief adaptation with an oriented stimulus, on the time scale of visual fixation. Adaptation with stimuli that are orthogonal to a neuron's preferred orientation does not alter the preferred orientation but sharpens orientation tuning. Thus, successive fixation on dissimilar image patches, as happens during natural vision, combined with mechanisms of rapid cortical plasticity, actually improves orientation discrimination. Finally, natural vision involves judgements about where to look next, based on an internal model of the visual world. Experiments in behaving monkeys in which information about future stimulus locations can be acquired in one set of trials but not in another demonstrate that V1 neurons signal the acquisition of internal representations. Such Bayesian updating of responses based on statistical learning is fundamental for higher level vision, for deriving inferences about the structure of the visual world, and for the regulation of eye movements.

Adaptation, Psychological↗
PubMed2004

Dendritic spine dynamics are regulated by monocular deprivation and extracellular matrix degradation.

The mammalian primary visual cortex (V1) is especially susceptible to changes in visual input over a well-defined critical period, during which closing one eye leads to a loss of responsiveness of neurons to the deprived eye and a shift in response toward the open eye. This functional plasticity can occur rapidly, following even a single day of eye closure, although the structural bases of these changes are unknown. Here, we show that rapid structural changes at the level of dendritic spines occur following brief monocular deprivation. These changes are evident in the supra- and infragranular layers of the binocular zone and can be mimicked by degradation of the extracellular matrix with the tPA/plasmin proteolytic cascade. Further, monocular deprivation occludes a subsequent effect of matrix degradation, suggesting that this mechanism is active in vivo to permit structural remodeling during ocular dominance plasticity.

Animals↗
PubMed2004

Acceleration of visually cued conditioned fear through the auditory pathway.

Defensive responses elicited by sensory experiences are critical for survival. Mice acquire a conditioned fear response rapidly to an auditory cue but slowly to a visual cue, a difference in learned behavior that is likely to be mediated by direct projections to the lateral amygdala from the auditory thalamus but mainly indirect ones from the visual thalamus. Here, we show that acquisition of visually cued conditioned fear is accelerated in 'rewired' mice that have retinal projections routed to the auditory thalamus. Visual stimuli induce expression of the immediate early gene Fos (also known as c-fos) in the auditory thalamus and the lateral amygdala in rewired mice, similar to the way auditory stimuli do in control mice. Thus, the rewired auditory pathway conveys visual information and mediates rapid activity-dependent plasticity in central structures that influence learned behavior.

Amygdala↗