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A classic example of experience-dependent plasticity is ocular dominance (OD) shift, in which the responsiveness of neurons in the visual cortex is profoundly altered following monocular deprivation (MD). It has been postulated that OD shifts also modify global neural networks, but such effects have never been demonstrated. Here, we use wide-field fluorescence optical imaging (WFOI) to characterize calcium-based resting-state functional connectivity during acute (3 d) MD in female and male mice with genetically encoded calcium indicators (Thy1-GCaMP6f). We first establish the fundamental performance of WFOI by computing signal to noise properties throughout our data processing pipeline. Following MD, we found that Δ band (0.4-4 Hz) GCaMP6 activity in the deprived visual cortex decreased, suggesting that excitatory activity in this region was reduced by MD. In addition, interhemispheric visual homotopic functional connectivity decreased following MD, which was accompanied by a reduction in parietal and motor homotopic connectivity. Finally, we observed enhanced internetwork connectivity between the visual and parietal cortex that peaked 2 d after MD. Together, these findings support the hypothesis that early MD induces dynamic reorganization of disparate functional networks including the association cortices. [ABSTRACT FROM AUTHOR]

Alzheimer's disease patients and mouse models exhibit aberrant neuronal activity and altered excitatory-to-inhibitory synaptic ratio. Using multicolor two-photon microscopy, we test how amyloid pathology alters the structural dynamics of excitatory and inhibitory synapses and their adaptation to altered visual experience in vivo in the visual cortex. We show that the baseline dynamics of mature excitatory synapses and their adaptation to visual deprivation are not altered in amyloidosis. Likewise, the baseline dynamics of inhibitory synapses are not affected. In contrast, visual deprivation fails to induce inhibitory synapse loss in amyloidosis, a phenomenon observed in nonpathological conditions. Intriguingly, inhibitory synapse loss associated with visual deprivation in nonpathological mice is accompanied by subtle broadening of spontaneous but not visually evoked calcium transients. However, such broadening does not manifest in the context of amyloidosis. We also show that excitatory and inhibitory synapse loss is locally clustered under the nonpathological state. In contrast, a fraction of synapse loss is not locally clustered in amyloidosis, indicating an impairment in inhibitory synapse adaptation to changes in excitatory synaptic activity. [ABSTRACT FROM AUTHOR]

The mammalian visual cortex contains multiple retinotopically defined areas that process distinct features of the visual scene. Little is known about what guides the functional differentiation of visual cortical areas during development. Recent studies in mice have revealed that visual input from the two eyes provides spatiotemporally distinct signals to primary visual cortex (V1), such that contralateral eye-dominated V1 neurons respond to higher spatial frequencies than ipsilateral eye-dominated neurons. To test whether binocular visual input drives the differentiation of visual cortical areas, we used two-photon calcium imaging to characterize the effects of juvenile monocular deprivation (MD) on the responses of neurons in V1 and two higher visual areas, LM (lateromedial) and PM (posteromedial). In adult mice of either sex, we find that MD prevents the emergence of distinct spatiotemporal tuning in V1, LM, and PM. We also find that, within each of these areas, MD reorganizes the distinct spatiotemporal tuning properties driven by the two eyes. Moreover, we find a relationship between speed tuning and ocular dominance in all three areas that MD preferentially disrupts in V1, but not in LM or PM. Together, these results reveal that balanced binocular vision during development is essential for driving the functional differentiation of visual cortical areas. The higher visual areas of mouse visual cortex may provide a useful platform for investigating the experience-dependent mechanisms that set up the specialized processing within neocortical areas during postnatal development.SIGNIFICANCE STATEMENT Little is known about the factors guiding the emergence of functionally distinct areas in the brain. Using in vivo Ca2+ imaging, we recorded visually evoked activity from cells in V1 and higher visual areas LM (lateromedial) and PM (posteromedial) of mice. Neurons in these areas normally display distinct spatiotemporal tuning properties. We found that depriving one eye of normal input during development prevents the functional differentiation of visual areas. Deprivation did not disrupt the degree of speed tuning, a property thought to emerge in higher visual areas. Thus, some properties of visual cortical neurons are shaped by binocular experience, while others are resistant. Our study uncovers the fundamental role of binocular experience in the formation of distinct areas in visual cortex.

Retinoic acid (RA) and its receptors (RARs) are well established essential transcriptional regulators during embryonic development. Recent findings in cultured neurons identified an independent and critical post-transcriptional role of RA and RARα in the homeostatic regulation of excitatory and inhibitory synaptic transmission in mature neurons. However, the functional relevance of synaptic RA signaling in vivo has not been established. Here, using somatosensory cortex as a model system and the RARα conditional knock-out mouse as a tool, we applied multiple genetic manipulations to delete RARα postnatally in specific populations of cortical neurons, and asked whether synaptic RA signaling observed in cultured neurons is involved in cortical information processing in vivo Indeed, conditional ablation of RARα in mice via a CaMKIIα-Cre or a layer 5-Cre driver line or via somatosensory cortex-specific viral expression of Cre-recombinase impaired whisker-dependent texture discrimination, suggesting a critical requirement of RARα expression in L5 pyramidal neurons of somatosensory cortex for normal tactile sensory processing. Transcranial two-photon imaging revealed a significant increase in dendritic spine elimination on apical dendrites of somatosensory cortical layer 5 pyramidal neurons in these mice. Interestingly, the enhancement of spine elimination is whisker experience-dependent as whisker trimming rescued the spine elimination phenotype. Additionally, experiencing an enriched environment improved texture discrimination in RARα-deficient mice and reduced excessive spine pruning. Thus, RA signaling is essential for normal experience-dependent cortical circuit remodeling and sensory processing.SIGNIFICANCE STATEMENT The importance of synaptic RA signaling has been demonstrated in in vitro studies. However, whether RA signaling mediated by RARα contributes to neural circuit functions in vivo remains largely unknown. In this study, using a RARα conditional knock-out mouse, we performed multiple regional/cell-type-specific manipulation of RARα expression in the postnatal brain, and show that RARα signaling contributes to normal whisker-dependent texture discrimination as well as regulating spine dynamics of apical dendrites from layer (L5) pyramidal neurons in S1. Deletion of RARα in excitatory neurons in the forebrain induces elevated spine elimination and impaired sensory discrimination. Our study provides novel insights into the role of RARα signaling in cortical processing and experience-dependent spine maturation.

Sensory loss leads to widespread cross-modal plasticity across brain areas to allow the remaining senses to guide behavior. While multimodal sensory interactions are often attributed to higher-order sensory areas, cross-modal plasticity has been observed at the level of synaptic changes even across primary sensory cortices. In particular, vision loss leads to widespread circuit adaptation in the primary auditory cortex (A1) even in adults. Here we report using mice of both sexes in which cross-modal plasticity occurs even earlier in the sensory-processing pathway at the level of the thalamus in a modality-selective manner. A week of visual deprivation reduced inhibitory synaptic transmission from the thalamic reticular nucleus (TRN) to the primary auditory thalamus (MGBv) without changes to the primary visual thalamus (dLGN). The plasticity of TRN inhibition to MGBv was observed as a reduction in postsynaptic gain and shortterm depression. There was no observable plasticity of the cortical feedback excitatory synaptic transmission from the primary visual cortex to dLGN or TRN and A1 to MGBv, which suggests that the visual deprivation-induced plasticity occurs predominantly at the level of thalamic inhibition. We provide evidence that visual deprivation-induced change in the short-term depression of TRN inhibition to MGBv involves endocannabinoid CB1 receptors. TRN inhibition is considered critical for sensory gating, selective attention, and multimodal performances; hence, its plasticity has implications for sensory processing. Our results suggest that selective disinhibition and altered short-term dynamics of TRN inhibition in the spared thalamic nucleus support cross-modal plasticity in the adult brain. [ABSTRACT FROM AUTHOR]

hMT+/V5 is a region in the middle occipitotemporal cortex that responds preferentially to visual motion in sighted people. In cases of early visual deprivation, hMT+/V5 enhances its response to moving sounds. Whether hMT+/V5 contains information about motion directions and whether the functional enhancement observed in the blind is motion specific, or also involves sound source location, remains unsolved. Moreover, the impact of this cross-modal reorganization of hMT+/V5 on the regions typically supporting auditory motion processing, like the human planum temporale (hPT), remains equivocal. We used a combined functional and diffusion-weighted MRI approach and individual in-ear recordings to study the impact of early blindness on the brain networks supporting spatial hearing in male and female humans. Whole-brain univariate analysis revealed that the anterior portion of hMT+/V5 responded to moving sounds in sighted and blind people, while the posterior portion was selective to moving sounds only in blind participants. Multivariate decoding analysis revealed that the presence of motion direction and sound position information was higher in hMT+/V5 and lower in hPT in the blind group. While both groups showed axis-of-motion organization in hMT+/V5 and hPT, this organization was reduced in the hPT of blind people. Diffusion-weighted MRI revealed that the strength of hMT+/V5--hPT connectivity did not differ between groups, whereas the microstructure of the connections was altered by blindness. Our results suggest that the axis-of-motion organization of hMT+/V5 does not depend on visual experience, but that congenital blindness alters the response properties of occipitotemporal networks supporting spatial hearing in the sighted. [ABSTRACT FROM AUTHOR]

In humans, sleep spindles are 10- to 16-Hz oscillations lasting approximately 0.5–2 s. Spindles, along with cortical slow oscillations, may facilitate memory consolidation by enabling synaptic plasticity. Early recordings of spindles at the scalp found anterior channels had overall slower frequency than central-posterior channels. This robust, topographical finding led to dichotomizing spindles as “slow” versus “fast,” modeled as two distinct spindle generators in frontal versus posterior cortex. Using a large dataset of intracranial stereoelectroencephalographic (sEEG) recordings from 20 patients (13 female, 7 male) and 365 bipolar recordings, we show that the difference in spindle frequency between frontal and parietal channels is comparable to the variability in spindle frequency within the course of individual spindles, across different spindles recorded by a given site, and across sites within a given region. Thus, fast and slow spindles only capture average differences that obscure a much larger underlying overlap in frequency. Furthermore, differences in mean frequency are only one of several ways that spindles differ. For example, compared with parietal, frontal spindles are smaller, tend to occur after parietal when both are engaged, and show a larger decrease in frequency within-spindles. However, frontal and parietal spindles are similar in being longer, less variable, and more widespread than occipital, temporal, and Rolandic spindles. These characteristics are accentuated in spindles which are highly phase-locked to posterior hippocampal spindles. We propose that rather than a strict parietal-fast/frontal-slow dichotomy, spindles differ continuously and quasi-independently in multiple dimensions, with variability due about equally to within-spindle, within-region, and between-region factors. [ABSTRACT FROM AUTHOR]

The opioid epidemic is a rapidly evolving societal issue driven, in part, by a surge in synthetic opioid use. A rise in fentanyl use among pregnant women has led to a 40-fold increase in the number of perinatally-exposed infants in the past decade. These children are more likely to develop mood-related and somatosensory-related conditions later in life, suggesting that fentanyl may permanently alter neural development. Here, we examined the behavioral and synaptic consequences of perinatal fentanyl exposure in adolescent male and female C57BL/6J mice and assessed the therapeutic potential of environmental enrichment to mitigate these effects. Dams were given ad libitum access to fentanyl (10 mg/ml, per os) across pregnancy and until weaning [postnatal day (PD)21]. Perinatally-exposed adolescent mice displayed hyperactivity (PD45), enhanced sensitivity to anxiogenic environments (PD46), and sensory maladaptation (PD47), sustained behavioral effects that were completely normalized by environmental enrichment (PD21-PD45). Additionally, environmental enrichment normalized the fentanylinduced changes in the frequency of miniature EPSCs (mEPSCs) of layer 2/3 neurons in the primary somatosensory cortex (S1). We also demonstrate that fentanyl impairs short-term potentiation (STP) and long-term potentiation (LTP) in S1 layer 2/3 neurons, which, instead, exhibit a sustained depression of synaptic transmission that is restored by environmental enrichment. On its own, environmental enrichment suppressed long-term depression (LTD) of control S1 neurons from vehicletreated mice subjected to standard housing conditions. These results demonstrate that the lasting effects of fentanyl can be ameliorated with a noninvasive intervention introduced during early development. [ABSTRACT FROM AUTHOR]

Malfunctioning synaptic plasticity is one of the major mechanisms contributing to the development of chronic pain. We studied spike-timing dependent depression (tLTD) in the anterior cingulate cortex (ACC) of male mice, a brain region involved in processing emotional aspects of pain. tLTD onto layer 5 pyramidal neurons depended on postsynaptic calcium-influx through GluN2B-containing NMDARs and retrograde signaling via nitric oxide to reduce presynaptic release probability. After chronic constriction injury of the sciatic nerve, a model for neuropathic pain, tLTD was rapidly impaired; and this phenotype persisted even beyond the time of recovery from mechanical sensitization. Exclusion of GluN2B-containing NMDARs from the postsynaptic site specifically at projections from the anterior thalamus to the ACC caused the tLTD phenotype, whereas signaling downstream of nitric oxide synthesis remained intact. Thus, transient neuropathic pain can leave a permanent trace manifested in the disturbance of synaptic plasticity in a specific afferent pathway to the cortex. [ABSTRACT FROM AUTHOR]

The axon initial segment (AIS), nodes of Ranvier, and the oligodendrocyte-derived myelin sheath have significant influence on the firing patterns of neurons and the faithful, coordinated transmission of action potentials (APs) to downstream brain regions. In the olfactory bulb (OB), olfactory discrimination tasks lead to adaptive changes in cell firing patterns, and the output signals must reliably travel large distances to other brain regions along highly myelinated tracts. Whether myelinated axons adapt to facilitate olfactory sensory processing is unknown. Here, we investigate the morphology and physiology of mitral cell (MC) axons in the olfactory system of adult male and female mice and show that unilateral sensory deprivation causes system-wide adaptations in axonal morphology and myelin thickness. MC spiking patterns and APs also adapted to sensory deprivation. Strikingly, myelination and MC physiology were altered on both the deprived and nondeprived sides, indicating system level adaptations to reduced sensory input. Our work demonstrates a previously unstudied mechanism of plasticity in the olfactory system. [ABSTRACT FROM AUTHOR]

The article focuses on the central goal of cognitive neuroscience which has been to interpret neural signals. Topics include examines to do so, it focuses on depicting commonalities between individuals at the population level and everyone's perception of the world is shaped differently by individual experiences and preferences averaging across participants may hide such peculiarities of specific individuals' brains.

Pyramidal neurons in layers 2/3 and 5 of primary somatosensory cortex (S1) exhibit somewhat modest synaptic plasticity after whisker input deprivation. Whether neurons involved at earlier steps of sensory processing show more or less plasticity has not yet been examined. Here, we used longitudinal in vivo two-photon microscopy to investigate dendritic spine dynamics in apical tufts of GFP-expressing layer 4 (L4) pyramidal neurons of the vibrissal (barrel) S1 after unilateral whisker trimming. First, we characterize the molecular, anatomical, and electrophysiological properties of identified L4 neurons in Ebf2-Cre transgenic mice. Next, we show that input deprivation results in a substantial (∼50%) increase in the rate of dendritic spine loss, acutely (4-8 d) after whisker trimming. This robust synaptic plasticity in L4 suggests that primary thalamic recipient pyramidal neurons in S1 may be particularly sensitive to changes in sensory experience. Ebf2-Cre mice thus provide a useful tool for future assessment of initial steps of sensory processing in S1.

The article presents the discussion on correction notice "Brief Sensory Deprivation Triggers Cell Type-Specific Structural and Functional Plasticity in Olfactory Bulb Neurons" published on March 10, 2021 issue.

Can alterations in experience trigger different plastic modifications in neuronal structure and function, and if so, how do they integrate at the cellular level? To address this question, we interrogated circuitry in the mouse olfactory bulb responsible for the earliest steps in odor processing. We induced experience-dependent plasticity in mice of either sex by blocking one nostril for one day, a minimally invasive manipulation that leaves the sensory organ undamaged and is akin to the natural transient blockage suffered during common mild rhinal infections. We found that such brief sensory deprivation produced structural and functional plasticity in one highly specialized bulbar cell type: axon-bearing dopaminergic neurons in the glomerular layer. After 24 h naris occlusion, the axon initial segment (AIS) in bulbar dopaminergic neurons became significantly shorter, a structural modification that was also associated with a decrease in intrinsic excitability. These effects were specific to the AIS-positive dopaminergic subpopulation because no experience-dependent alterations in intrinsic excitability were observed in AIS-negative dopaminergic cells. Moreover, 24 h naris occlusion produced no structural changes at the AIS of bulbar excitatory neurons, mitral/tufted and external tufted cells, nor did it alter their intrinsic excitability. By targeting excitability in one specialized dopaminergic subpopulation, experience-dependent plasticity in early olfactory networks might act to fine-tune sensory processing in the face of continually fluctuating inputs. [ABSTRACT FROM AUTHOR]

Signal detection theory (SDT) is a widely used theoretical framework that describes how variable sensory signals are integrated with a decision criterion to support perceptual decision-making. SDT provides two key measurements: sensitivity (d') and bias (c), which reflect the separability of decision variable distributions (signal and noise) and the position of the decision criterion relative to optimal, respectively. Although changes in the subject's decision criterion can be reflected in changes in bias, decision criterion placement is not the sole contributor to measured bias. Indeed, neuronal representations of bias have been observed in sensory areas, suggesting that some changes in bias are because of effects on sensory encoding. To directly test whether the sensory encoding process can influence bias, we optogenetically manipulated neuronal excitability in primary visual cortex (V1) in mice of both sexes during either an orientation discrimination or a contrast detection task. Increasing excitability in V1 significantly decreased behavioral bias, whereas decreasing excitability had the opposite effect. To determine whether this change in bias is consistent with effects on sensory encoding, we made extracellular recordings from V1 neurons in passively viewing mice. Indeed, we found that optogenetic manipulation of excitability shifted the neuronal bias in the same direction as the behavioral bias. Moreover, manipulating the quality of V1 encoding by changing stimulus contrast or interstimulus interval also resulted in consistent changes in both behavioral and neuronal bias. Thus, changes in sensory encoding are sufficient to drive changes in bias measured using SDT. [ABSTRACT FROM AUTHOR]

During a critical period in development, spontaneous and evoked retinal activity shape visual pathways in an adaptive fashion. Interestingly, spontaneous activity is sufficient for spatial refinement of visual receptive fields (RFs) in superior colliculus (SC) and visual cortex (V1), but early visual experience is necessary to maintain inhibitory synapses and stabilize RFs in adulthood (Carrasco et ah, 2005,2011; Carrasco and Pallas, 2006; Balmer and Pallas, 2015a). In VI, BDNF and its high-affinity receptor TrkB are important for development of visual acuity, inhibition, and regulation of the critical period for ocular dominance plasticity (Flanover et ah, 1999; Huang et al„ 1999; Gianfranceschi et al., 2003). To examine the generality of this signaling pathway for visual system plasticity, the present study examined the role of TrkB signaling during the critical period for RF refinement in SC. Activating TrkB receptors during the critical period (P33-P40) in dark reared subjects produced normally refined RFs, and blocking TrkB receptors in light-exposed animals resulted in enlarged adult RFs like those in dark reared animals. We also report here that deprivation- or TrkB blockade-induced RF enlargement in adulthood impaired fear responses to looming overhead stimuli and negatively impacted visual acuity. Thus, early TrkB activation is both necessary and sufficient to maintain visual RF refinement, robust looming responses, and visual acuity in adulthood. These findings suggest a common signaling pathway exists for the maturation of inhibition between VI and SC. [ABSTRACT FROM AUTHOR]

Sensory information is encoded by populations of cortical neurons. Yet, it is unknown how this information is used for even simple perceptual choices such as discriminating orientation. To determine the computation underlying this perceptual choice, we took advantage of the robust visual adaptation in mouse primary visual cortex (V1). We first designed a stimulus paradigm in which we could vary the degree of neuronal adaptation measured in V1 during an orientation discrimination task. We then determined how adaptation affects task performance for mice of both sexes and tested which neuronal computations are most consistent with the behavioral results given the adapted population responses in V1. Despite increasing the reliability of the population representation of orientation among neurons, and improving the ability of a variety of optimal decoders to discriminate target from distractor orientations, adaptation increases animals’ behavioral thresholds. Decoding the animals’ choice from neuronal activity revealed that this unexpected effect on behavior could be explained by an overreliance of the perceptual choice circuit on target preferring neurons and a failure to appropriately discount the activity of neurons that prefer the distractor. Consistent with this all-positive computation, we find that animals’ task performance is susceptible to subtle perturbations of distractor orientation and optogenetic suppression of neuronal activity in V1. This suggests that to solve this task the circuit has adopted a suboptimal and task-specific computation that discards important task-related information. [ABSTRACT FROM AUTHOR]

Brain activity patterns exhibited during task performance have been shown to spontaneously reemerge in the following restful awake state. Such "awake reactivation" has been observed across higher-order cortex for complex images or associations. However, it is still unclear whether the reactivation extends to primary sensory areas that encode simple stimulus features. To address this question, we trained human subjects from both sexes on a particular visual feature (Gabor orientation) and tested whether this feature will be reactivated immediately after training. We found robust reactivation in human V1 that lasted for at least 8 min after training offset. This effect was not present in higher retinotopic areas, such as V2, V3, V3A, or V4v. Further analyses suggested that the amount of awake reactivation was related to the amount of performance improvement on the visual task. These results demonstrate that awake reactivation extends beyond higher-order areas and also occurs in early sensory cortex. [ABSTRACT FROM AUTHOR]

Neural circuits are shaped by experience during critical periods of development. Sensory deprivation during these periods permanently compromises an organism's ability to perceive the outside world. In the mouse visual system, normal visual experience during a critical period in early life drives the matching of individual cortical neurons' orientation preferences through the two eyes, likely a key step in the development of binocular vision. Here, in mice of both sexes, we show that the binocular matching process is completely blocked by monocular deprivation spanning the entire critical period. We then show that 3 weeks of environmental enrichment (EE), a paradigm of enhanced sensory, motor, and cognitive stimulation, is sufficient to rescue binocular matching to the level seen in unmanipulated mice. In contrast, 6 weeks of conventional housing only resulted in a partial rescue. Finally, we use two-photon calcium imaging to track the matching process chronically in individual cells during EE-induced rescue. We find that for cells that are clearly dominated by one of the two eyes, the input representing the weaker eye changes its orientation preference to align with that of the dominant eye. These results thus reveal ocular dominance as a key driver of the binocular matching process, and suggest a model whereby the dominant input instructs the development of the weaker input. Such a mechanism may operate in the development of other systems that need to integrate inputs from multiple sources to generate normal neuronal functions. [ABSTRACT FROM AUTHOR]

Sensory pathways display heightened plasticity during development, yet the perceptual consequences of early experience are generally assessed in adulthood. This approach does not allow one to identify transient perceptual changes that may be linked to the central plasticity observed in juvenile animals. Here, we determined whether a brief period of bilateral auditory deprivation affects sound perception in developing and adult gerbils. Animals were reared with bilateral earplugs, either from postnatal day 11 (P11) to postnatal day 23 (P23) (a manipulation previously found to disrupt gerbil cortical properties), or from P23-P35. Fifteen days after earplug removal and restoration of normal thresholds, animals were tested on their ability to detect the presence of amplitude modulation (AM), a temporal cue that supports vocal communication. Animals reared with earplugs from P11-P23 displayed elevated AM detection thresholds, compared with age-matched controls. In contrast, an identical period of earplug rearing at a later age (P23-P35) did not impair auditory perception. Although the AM thresholds of earplug-reared juveniles improved during a week of repeated testing, a subset of juveniles continued to display a perceptual deficit. Furthermore, although the perceptual deficits induced by transient earplug rearing had resolved for most animals by adulthood, a subset of adults displayed impaired performance. Control experiments indicated that earplugging did not disrupt the integrity of the auditory periphery. Together, our results suggest that P11-P23 encompasses a critical period during which sensory deprivation disrupts central mechanisms that support auditory perceptual skills. [ABSTRACT FROM AUTHOR]

There is substantial evidence that sensory deprivation leads to important cross-modal brain reorganization that is paralleled by enhanced perceptual abilities. However, it remains unclear how widespread these enhancements are, and whether they are intercorrelated or arise at the expense of other perceptual abilities. One specific area where such a trade-off might arise is that of spatial hearing, where blind individuals have been shown to possess superior monaural localization abilities in the horizontal plane, but inferior localization abilities in the vertical plane. While both of these tasks likely involve the use of monaural cues due to the absence of any relevant binaural signal, there is currently no proper explanation for this discrepancy, nor has any study investigated both sets of abilities in the same sample of blind individuals. Here, we assess whether the enhancements observed in the horizontal plane are related to the deficits observed in the vertical plane by testing sound localization in both planes in groups of blind and sighted persons. Our results show that the blind individuals who displayed the highest accuracy at localizing sounds monaurally in the horizontal plane are also the ones who exhibited the greater deficit when localizing in the vertical plane. These findings appear to argue against the idea of generalized perceptual enhancements in the early blind, and instead suggest the possibility of a trade-off in the localization proficiency between the two auditory spatial planes, such that learning to use monaural cues for the horizontal plane comes at the expense of using those cues to localize in the vertical plane. [ABSTRACT FROM AUTHOR]

Classical conditioning that involves mnemonic processing, that is, a "trace" period between conditioned and unconditioned stimulus, requires awareness of the association to be formed and is considered a simple model paradigm for declarative learning. Barrel cortex, the whisker representation of primary somatosensory cortex, is required for the learning of a tactile variant of trace eyeblink conditioning (TTEBC) and undergoes distinct map plasticity during learning. To investigate the cellular mechanism underpinning TTEBC and concurrent map plasticity, we used two-photon imaging of dendritic spines in barrel cortex of awake mice while being conditioned. Monitoring layer 5 neurons' apical dendrites in layer 1, we show that one cellular expression of barrel cortex plasticity is a substantial spine count reduction of ~ 15% of the dendritic spines present before learning. The number of eliminated spines and their time of elimination are tightly related to the learning success. Moreover, spine plasticity is highly specific for the principal barrel column receiving the main signals from the stimulated vibrissa. Spines located in other columns, even those directly adjacent to the principal column, are unaffected. Because layer 1 spines integrate signals from associative thalamocortical circuits, their column-specific elimination suggests that this spine plasticity may be the result of an association of top-down signals relevant for declarative learning and spatially precise ascending tactile signals. [ABSTRACT FROM AUTHOR]

Although it is well known that injury induces the generation of a substantial number of new olfactory sensory neurons (OSNs) in the adult olfactory epithelium (OE), it is not well understood whether olfactory sensory input influences the survival and maturation of these injury-induced OSNs in adults. Here, we investigated whether olfactory sensory deprivation affected the dynamic incorporation of newly generated OSNs 3, 7,14, and 28 d after injury in adult mice. Mice were unilaterally deprived of olfactory sensory input by inserting a silicone tube into their nostrils. Methimazole, an olfactotoxic drug, was also injected intraperitoneal to bilaterally ablate OSNs. The OE was restored to its preinjury condition with new OSNs by day 28. No significant differences in the numbers of olfactory marker proteinpositive mature OSNs or apoptotic OSNs were observed between the deprived and nondeprived sides 0 - 7 d after injury. However, between days 7 and 28, the sensory-deprived side showed markedly fewer OSNs and mature OSNs, but more apoptotic OSNs, than the nondeprived side. Intrinsic functional imaging of the dorsal surface of the olfactory bulb at day 28 revealed that responses to odor stimulation were weaker in the deprived side compared with those in the nondeprived side. Furthermore, prevention of cell death in new neurons 7-14 d after injury promoted the recovery of the OE. These results indicate that, in the adult OE, sensory deprivation disrupts compensatory OSN regeneration after injury and that newly generated OSNs have a critical time window for sensory-input-dependent survival 7-14 d after injury. [ABSTRACT FROM AUTHOR]

A key question in Huntington's disease (HD) is what underlies the early cognitive deficits that precede the motor symptoms and the characteristic neuronal death observed in HD. The mechanisms underlying cognitive symptoms in HD remain unknown. Postmortem HD brain and animal model studies demonstrate pathologies in dendritic spines and abnormal synaptic plasticity before motor symptoms and neurodegeneration. Experience-dependent synaptic plasticity caused by mechanisms such as LTP or novel sensory experience potentiates synaptic strength, enhances new dendritic spine formation and stabilization, and may contribute to normal cognitive processes, such as learning and memory. We have previously reported that under baseline conditions (without any sensory manipulation) neuronal circuitry in HD (R6/2 mouse model) was highly unstable, which led to a progressive loss of persistent spines in these mice, and that mutant huntingtin was directly involved in the process. Here, we investigated whether pathological processes of HD interfere with the normal experience-dependent plasticity of dendritic spines in the R6/2 model. Six weeks of two-photon in vivo imaging before and after whisker trimming revealed that sensory deprivation exacerbates loss of persistent-type, stable spines in R6/2 mice compared with wild-type littermates. In addition, sensory deprivation leads to impaired transformation of newly generated spines into persistent spines in R6/2 mice. As a consequence, reduced synaptic density and decreased PSD-95 protein levels are evident in their barrel cortical neurons. These data suggest that mutant huntingtin is implicated in maladaptive synaptic plasticity, which could be one of the plausible mechanisms underlying early cognitive deficits in HD. [ABSTRACT FROM AUTHOR]

Cortical networks can maintain memories for decades despite the short lifetime of synaptic strengths. Can a neural network store long-lasting memories in unstable synapses? Here, we study the effects of ongoing spike-timing-dependent plasticity (STDP) on the stability of memory patterns stored in synapses of an attractor neural network. We show that certain classes of STDP rules can stabilize all stored memory patterns despite a short lifetime of synapses. In our model, unstructured neural noise, after passing through the recurrent network connections, carries the imprint of all memory patterns in temporal correlations. STDP, combined with these corre-lations, leads to reinforcement of all stored patterns, even those that are never explicitly visited. Our findings may provide the functional reason for irregular spiking displayed by cortical neurons and justify models of system memory consolidation. Therefore, we propose that irregular neural activity is the feature that helps cortical networks maintain stable connections. [ABSTRACT FROM AUTHOR]

The article presents the discussion on role for Kinesin KIFC in nuclear migration. Topics include first cells of the developing nervous system being radial glial cells such as the progenitors of neurons and astrocytes; and moving the nucleus along microtubules toward the leading process of migrating newborn neurons.

We previously reported in adult mice that visuomotor experience during monocular deprivation (MD) augmented enhancement of visual-cortex-dependent behavior through the non-deprived eye (NDE) during deprivation, and enabled enhanced function to persist after MD. We investigated the physiological substrates of this experience-enabled form of adult cortical plasticity by measuring visual behavior and visually evoked potentials (VEPs) in binocular visual cortex of the same mice before, during, and after MD. MD on its own potentiated VEPs contralateral to the NDE during MD and shifted ocular dominance (OD) in favor of the NDE in both hemispheres. Whereas we expected visuomotor experience during MD to augment these effects, instead enhanced responses contralateral to the NDE, and the OD shift ipsilateral to the NDE were attenuated. However, in the same animals, we measured NMDA receptor-dependent VEP potentiation ipsilateral to the NDE during MD, which persisted after MD. The results indicate that visuomotor experience during adult MD leads to enduring enhancement of behavioral function, not simply by amplifying MD-induced changes in cortical OD, but through an independent process of increasing NDE drive in ipsilateral visual cortex. Because the plasticity is resident in the mature visual cortex and selectively effects gain of visual behavior through experiential means, it may have the therapeutic potential to target and non-invasively treat eye- or visual-field-specific cortical impairment. [ABSTRACT FROM AUTHOR]

Sparse redundancy reducing codes have been proposed as efficient strategies for representing sensory stimuli. A prevailing hypothesis suggests that sensory representations shift from dense redundant codes in the periphery to selective sparse codes in cortex. We propose an alternative framework where sparseness and redundancy depend on sensory integration time scales and demonstrate that the central nucleus of the inferior colliculus (ICC) of cats encodes sound features by precise sparse spike trains. Direct comparisons with auditory cortical neurons demonstrate that ICC responses were sparse and uncorrelated as long as the spike train time scales were matched to the sensory integration time scales relevant to ICC neurons. Intriguingly, correlated spiking in the ICC was substantially lower than predicted by linear or nonlinear models and strictly observed for neurons with best frequencies within a "critical band," the hallmark of perceptual frequency resolution in mammals. This is consistent with a sparse asynchronous code throughout much of the ICC and a complementary correlation code within a critical band that may allow grouping of perceptually relevant cues. [ABSTRACT FROM AUTHOR]

Sensory experience in early postnatal life shapes neuronal connections in the brain. Here we report that the local synthesis of brainderived neurotrophic factor (BDNF) in dendrites plays an important role in this process. We found that dendritic spines of layer 2/3 pyramidal neurons of the visual cortex in mutant mice lacking dendritic Bdnf mRNA and thus local BDNF synthesis were normal at 3 weeks of age, but thinner, longer, and more closely spaced (morphological features of immaturity) at 4 months of age than in wild-type (WT) littermates. Layer 2/3 of the visual cortex in these mutant animals also had fewer GABAergic presynaptic terminals at both ages. The overall size and shape of dendritic arbors were, however, similar in mutant and WTmice at both ages. By using optical imaging of intrinsic signals and single-unit recordings, we found that mutant animals failed to recover cortical responsiveness following monocular deprivation (MD) during the critical period, although they displayed normally the competitive loss of responsiveness to an eye briefly deprived of vision. Furthermore,MDstill induced a loss of responsiveness to the closed eye in adult mutant mice, but not in adultWTmice. These results indicate that dendritic BDNF synthesis is required for spine pruning, late-phase spine maturation, and recovery of cortical responsiveness following sensory deprivation. They also suggest that maturation of dendritic spines is required for the maintenance of cortical responsiveness following sensory deprivation in adulthood. [ABSTRACT FROM AUTHOR]

The mechanism of amblyopia in children with congenital cataract is not understood fully, but studies in macaques have shown that geniculate synapses are lost in striate cortex (V1). To search for other projection abnormalities in amblyopia, the pathway from V1 to V2 was examined using a triple-label technique in three animals raised with monocular suture. [ 3H]proline was injected into one eye to label the ocular dominance columns. Cholera toxin B subunit conjugated to gold (CTB-Au) was injected into V2 to label V1 projection neurons. Alternate sections were processed for cytochrome oxidase (CO) and CTB-Au, or dipped for autoradiography. Eight fields of CTB-Aulabeled cells in V1 opposite injection sites were plotted in layers 2/3 or 4B. After thin stripe injection, labeled cells were concentrated inCO patches. Despite column shrinkage, cells in deprived and normal columns were equal in size and density in both layers 2/3 and 4B. After pale or thick stripe injection, labeled cells were concentrated in interpatches. Only 23% of projection neurons originated from deprived columns. This reduction exceeded the degree of column shrinkage, a result explained by the fact that column shrinkage causes disproportionate loss of interpatch territory. These data indicate that early monocular form deprivation does not alter the segregation of patch and interpatchpathwaystoV2stripes or cause selective loss or atrophy ofV1projection neurons.Theeffect of shrinkage of geniculocortical afferents in layer 4C following visual deprivation is not amplified further by attenuation of the amblyopic eye's projections from V1 to V2. [ABSTRACT FROM AUTHOR]

When delivered within 1 and in most cases 2 h of permanent middle cerebral artery occlusion (pMCAO), mild sensory stimulation (intermittent single whisker stimulation) was shown to be completely neuroprotective 24 h after pMCAO in a rodent model of ischemic stroke, according to assessment with multiple techniques (Lay et al., 2010). The acute effect of stimulation treatment on the ischemic cortex, however, has yet to be reported. Here we characterize cortical function and perfusion during the 120 min whisker stimulation period in four experimental groups with treatment initiated 0, 1, 2 (protected groups), or 3 h (unprotected group) post-pMCAO using multiple techniques. According to functional imaging, a gradual return of evoked whisker functional representation to baseline levels was initiated with treatment onset and completed within the treatment period. Evoked neuronal activity and reperfusion to the ischemic area also showed a gradual recovery in protected animals. Surprisingly, a similar recovery profile was observed in response to treatment in all protected animals, regardless of treatment onset time. Nonstimulated pMCAO control group data demonstrate that reperfusion is not spontaneous. This makes the complete protection observed in the majority of animals stimulated at 2 h post-pMCAO even more surprising, as these animals recovered despite having been in a severely ischemic state for two full hours. In summary, when delivered within a 2 h window post-pMCAO, whisker stimulation treatment initiated reperfusion and a gradual recovery of cortical function that was completed or nearly completed within the treatment period. [ABSTRACT FROM AUTHOR]

Surround suppression contributes to important functions in visual processing, such as figure-ground segregation; however, this benefit comes at the cost of decreased neuronal sensitivity. Studies of receptive fields at several levels of the visual hierarchy have demonstrated that surround suppression is reduced for low contrast stimuli, thereby improving neuronal sensitivity. We investigated whether this reduction of surround suppression reflects a general processing strategy to boost sensitivity for weak signals by summing them over a larger region of the visual field (spatial integration) or if the reduction is limited to specialized stimulus conditions. To do this, we used stochastic motion stimuli to measure surround suppression in area MT of alert macaque monkeys. While varying stimulus size we also varied the strength of two other critical stimulus features: contrast and coherence (i.e., the proportion of dots moving in the preferred direction of the neuron). We found that reducing stimulus contrast weakened surround suppression, but reducing stimulus coherence had the opposite effect, indicating that diminished surround suppression is not a universal response to stimuli of low signal-to-noise. This can be partially explained by our other finding, which is that surrounds in MT are very broadly direction tuned. Instead of producing a reduction of surround suppression that would improve the ability of the neuron to integrate preferred direction motion, low coherence stimuli activated the broadly tuned surrounds relatively better than the centers, which are generally more direction selective. Our results are consistent with a normalization mechanism of surround suppression that pools broadly across multiple stimulus dimensions. [ABSTRACT FROM AUTHOR]

We report that activation of GABAA receptors on cerebellar granule cell axons modulates both transmitter release and the excitability of the axon and soma. Axonal GABAA receptors depolarize the axon, increasing its excitability and causing calcium influx at axonal varicosities. GABA-mediated subthreshold depolarizations in the axon spread electrotonically to the soma, promoting orthodromic action potential initiation. When chloride concentrations are unperturbed, GABA iontophoresis elicits spikes and increases excitability of parallel fibers, indicating that GABAA receptor-mediated responses are normally depolarizing. GABA release from molecular layer interneurons activates parallel fiber GABAA receptors, and this, in turn, increases release probability at synapses between parallel fibers and molecular layer interneurons. These results describe a positive feedback mechanism whereby transmission from granule cells to Purkinje cells and molecular layer interneurons will be strengthened during granule cell spike bursts evoked by sensory stimulation. [ABSTRACT FROM AUTHOR]

The neural code that represents the world is transformed at each stage of a sensory pathway. These transformations enable downstream neurons to recode information they receive from earlier stages. Using the retinothalamic synapse as a model system, we developed a theoretical framework to identify stimulus features that are inherited, gained, or lost across stages. Specifically,we observed that thalamic spikes encode novel, emergent, temporal features not conveyed by single retinal spikes. Furthermore, we found that thalamic spikes are not only more informative than retinal ones, as expected, but also more independent. Next, we asked how thalamic spikes gain sensitivity to the emergent features. Explicitly, we found that the emergent features are encoded by retinal spike pairs and then recoded into independent thalamic spikes. Finally, we built a model of synaptic transmission that reproduced our observations. Thus, our results established a link between synaptic mechanisms and the recoding of sensory information. [ABSTRACT FROM AUTHOR]

Experimental neurophysiology and functional neuroimaging have identified a dorsal attention network that encodes neural signals related to the behavioral significance of a stimulus. The core anatomical areas of this network are the frontal eye fields and the posterior parietal cortex, which are interconnected by the superior longitudinal fasciculus. Here, we show that damage or disconnection of this network predicts the extent to which task-relevant stimuli capture attention of human stroke patients with spatial neglect. Healthy volunteers, right-hemisphere-damaged control participants, and patients with left neglect reacted to peripheral targets defined by their color, which were preceded by a brief distracter stimulus. The position of the distracter and its relevance for the current trial were independently varied. In neglect patients with damage including the frontal eye fields and the superior longitudinal fasciculus, ipsilesional distracters impaired orienting into contralesional space regardless of their relevance for the current task. In contrast, patients with sparing of these regions were only impaired when distracters were task-relevant. These findings indicate that the dorsal attention network controls spatial orienting by modulating the saliency of distracter stimuli according to current action goals. [ABSTRACT FROM AUTHOR]

Inhibition of return (IOR), a performance decrement for stimuli appearing at recently cued locations, occurs when the target and cue share the same screen position. This is in contrast to cue-based attention facilitation effects that were recently suggested to be mapped in a retinotopic reference frame, the prevailing representation throughout early visual processing stages. Here, we investigate the dynamics of IOR in both reference frames, using a modified cued-location saccadic reaction time task with an intervening saccade between cue and target presentation. Thus, on different trials, the target was present either at the same retinotopic location as the cue, or at the same screen position (e.g., spatiotopic location). IOR was primarily found for targets appearing at the same spatiotopic position as the initial cue, when the cue and target were presented at the same hemifield. This suggests that there is restricted information transfer of cue position across the two hemispheres. Moreover, the effect was maximal when the target was presented 10 ms after the intervening saccade ended and was attenuated in longer delays. In our case, therefore, the representation of previously attended locations (as revealed by IOR) is not remapped slowly after the execution of a saccade. Rather, either a retinotopic representation is remapped rapidly, adjacent to the end of the saccade (using a prospective motor command), or the positions of the cue and target are encoded in a spatiotopic reference frame, regardless of eye position. Spatial attention can therefore be allocated to target positions defined in extraretinal coordinates. [ABSTRACT FROM AUTHOR]

The role of spike rate versus timing codes in visual target selection is unclear. We simultaneously recorded activity from multiple frontal eye field neurons and asked whether they interacted to select targets from distractors during visual search. When both neurons in a pair selected the target and had overlapping receptive fields (RFs), they cooperated more than when one or neither neuron in the pair selected the target, measured by positive spike timing correlations using joint peristimulus time histogram analysis. The amount of cooperation depended on the location of the search target: it was higher when the target was inside both neurons' RFs than when it was inside one RF but not the other, or outside both RFs. Elevated spike timing coincidences occurred at the time of attentional selection of the target as measured by average modulation of discharge rates. We observed competition among neurons with spatially non-overlapping RFs, measured by negative spike timing correlations. Thus, we provide evidence for dynamic and task-dependent cooperation and competition among frontal eye field neurons during visual target selection. [ABSTRACT FROM AUTHOR]

It is well established that humans can react more quickly to a visual stimulus in the visual field center than to one in the visual periphery and that the reaction to a stimulus in the visual periphery markedly deteriorates with aging. These tendencies are true in conventional discrimination-reaction tasks. Surprisingly, however, we found that they are entirely different when reactions are induced by the same visual stimuli during reaching movements. The reaction time for a stimulus in the visual periphery was significantly faster than in the central vision, and age-related slowing of reactions to the stimulus in the visual periphery were quite small, compared to that observed in the conventional reaction tasks. This inconsistent slowing of reactions in different motor conditions underscores a distinctive visuomotor pathway for online control, which is more robust against age-related deterioration. [ABSTRACT FROM AUTHOR]

New neurons integrate in large numbers into the mature olfactory bulb circuit throughout life. The factors controlling the synaptic development of adult-born neurons and their connectivity remain essentially unknown. We examined the role of activity-dependent mechanisms in the synaptic development of adult-born neurons by genetic labeling of synapses while manipulating sensory input or cell-intrinsic excitability. Sensory deprivation induced marked changes in the density of input and output synapses during the period when new neurons develop most of their synapses. In contrast, when sensory deprivation started after synaptic formation was complete, input synapses increased in one domain without detectable changes in the other dendritic domains. We then investigated the effects of genetically raising the intrinsic excitability of new neurons on their synaptic development by delivering a voltage-gated sodium channel that triggers long depolarizations. Surprisingly, genetically increasing excitability did not affect synaptic development but rescued the changes in glutamatergic input synapses caused by sensory deprivation. These experiments show that, during adult neurogenesis in the olfactory bulb, synaptic plasticity is primarily restricted to an early period during the maturation of new neurons when they are still forming synapses. The addition of cells endowed with such an initial short-lived flexibility and long-term stability may enable the processing of information by the olfactory bulb to be both versatile and reliable in the face of changing behavioral demands. [ABSTRACT FROM AUTHOR]

Climbing fiber input produces complex spike synchrony across populations of cerebellar Purkinje cells oriented in the parasagittal axis. Elucidating the fine spatial structure of this synchrony is crucial for understanding its role in the encoding and processing of sensory information within the olivocerebellar cortical circuit. We investigated these issues using in vivo multineuron two-photon calcium imaging in combination with information theoretic analysis. Spontaneous dendritic calcium transients linked to climbing fiber input were observed in multiple neighboring Purkinje cells. Spontaneous synchrony of calcium transients between individual Purkinje cells falls off over ~200 μm mediolaterally, consistent with the presence of cerebellar microzones organized by climbing fiber input. Synchrony was increased after administration of harmaline, consistent with an olivary origin. Periodic sensory stimulation also resulted in a transient increase of synchrony after stimulus onset. To examine how synchrony affects the neural population code provided by the spatial pattern of complex spikes, we analyzed its information content. We found that spatial patterns of calcium events from small ensembles of cells provided substantially more stimulus information (59% more for seven-cell ensembles) than available by counting events across the pool without taking into account spatial origin. Information theoretic analysis indicated that, rather than contributing significantly to sensory coding via stimulus dependence, correlational effects on sensory coding are dominated by redundancy attributable to the prevalent spontaneous synchrony. The olivocerebellar circuit thus uses a labeled line code to report sensory signals, leaving open a role for synchrony in flexible selection of signals for output to deep cerebellar nuclei. [ABSTRACT FROM AUTHOR]

Instrumental behavior can be controlled by goal-directed action- outcome and habitual stimulus-response processes that are supported by anatomically distinct brain systems. Based on previous findings showing that stress modulates the interaction of "cognitive" and "habit" memory systems, we asked in the presented study whether stress may coordinate goal-directed and habit processes in instrumental learning. For this purpose, participants were exposed to stress (socially evaluated cold pressor test) or a control condition before they were trained to perform two instrumental actions that were associated with two distinct food outcomes. After training, one of these food outcomes was selectively devalued as subjects were saturated with that food. Next, subjects were presented the two instrumental actions in extinction. Stress before training in the instrumental task rendered participants' behavior insensitive to the change in the value of the food outcomes, that is stress led to habit performance. Moreover, stress reduced subjects' explicit knowledge of the action- outcome contingencies. These results demonstrate for the first time that stress promotes habits at the expense of goal-directed performance in humans. [ABSTRACT FROM AUTHOR]

Several theories have proposed a functional role for synchronous neuronal firing in generating the neural code of a sensory perception. Synchronous neural activity develops during a critical postnatal period of cortical maturation, and severely reducing neural activity in a sensory pathway during this period could interfere with the development of coincident discharge among cortical neurons. Loss of such synchrony could provide a fundamental mechanism for the degradation of acuity shown in behavioral studies. We tested the hypothesis that synchronous discharge of barrel cortex neurons would fail to develop after sensory deprivation produced by bilateral whisker trimming from birth to postnatal day 60. By studying the correlated discharge of cortical neuron pairs, we found evidence for strong correlated firing in control animals, and this synchrony was almost absent among pairs of cortical barrel neurons in deprived animals. The degree of synchrony impairment was different in subregions of rat barrel cortex. The model that best fits the data is that cortical neurons receiving direct inputs from the primary sensory (lemniscal) pathway show the greatest decrement in synchrony following sensory deprivation, while neurons with diverse inputs from other areas of thalamus and cortex are relatively less affected in this dimension of cortical function. [ABSTRACT FROM AUTHOR]

Several theories have proposed a functional role for synchronous neuronal firing in generating the neural code of a sensory perception. Synchronous neural activity develops during a critical postnatal period of cortical maturation, and severely reducing neural activity in a sensory pathway during this period could interfere with the development of coincident discharge among cortical neurons. Loss of such synchrony could provide a fundamental mechanism for the degradation of acuity shown in behavioral studies. We tested the hypothesis that synchronous discharge of barrel cortex neurons would fail to develop after sensory deprivation produced by bilateral whisker trimming from birth to postnatal day 60. By studying the correlated discharge of cortical neuron pairs, we found evidence for strong correlated firing in control animals, and this synchrony was almost absent among pairs of cortical barrel neurons in deprived animals. The degree of synchrony impairment was different in subregions of rat barrel cortex. The model that best fits the data is that cortical neurons receiving direct inputs from the primary sensory (lemniscal) pathway show the greatest decrement in synchrony following sensory deprivation, while neurons with diverse inputs from other areas of thalamus and cortex are relatively less affected in this dimension of cortical function. [ABSTRACT FROM AUTHOR]

The developing nervous system is shaped in important ways by spontaneous and stimulus-driven neural activity. Perturbation of normal activity patterns can profoundly affect the development of some neural response properties, whereas others are preserved through mechanisms that either compensate for or are unaffected by the perturbation. Most studies have examined the role of excitation in activity-dependent plasticity of response properties. Here, we examine the role of inhibition within the context of response selectivity for moving stimuli. The spatial extent of retinal input to the developing hamster superior colliculus (SC) can be experimentally increased by chronic NMDA receptor (NMDAR) blockade. Remarkably, stimulus velocity tuning is intact despite the increase in excitatory inputs. The goal of this study was to investigate whether plasticity in surround inhibition might provide the mechanism underlying this preservation of velocity tuning. Surround inhibition shapes velocity tuning in the majority of superficial layer SC neurons in normal hamsters. We show that despite the NMDAR blockade-induced increase in feed forward excitatory convergence from the retina, stimulus velocity tuning in the SC is maintained via compensatory plasticity in surround inhibition. The inhibitory surround increased in strength and spatial extent, and surround inhibition made a larger contribution to velocity tuning in the SC after chronic NMDAR blockade. These results show that inhibitory plasticity can preserve the balance between excitation and inhibition that is necessary to preserve response properties after developmental manipulations of neural activity. Understanding these compensatory mechanisms may permit their use to facilitate recovery from trauma or sensory deprivation. [ABSTRACT FROM AUTHOR]

During postnatal development, sensory experiences play critical roles in the refinement of cortical connections. However, both the process of postnatal experience-dependent maturation of neocortical inhibitory networks and its underlying mechanisms remain elusive. Here, we examined the differential properties of intracortical inhibitory networks of layer IV in "sensory-spared" and "sensory-deprived" cortices of glutamate acid decarboxylase 67 (GAD67)--green fluorescent protein (GFP) (Δneo) and wild-type mouse. Our results showed that row D whisker trimming (WT) begun at postnatal day 7 (P7), but not after P15, induced a robust reduction of parvalbumin (PV) expression, measured by the PV/GFP ratio and PV cell densities, in the deprived barrels. WT also induced a robust reduction in the number of inhibitory perisomatic varicosities and synaptic GAD65/67 immunoreactivities in spiny neurons of the deprived barrels. Although the GAD65/67 expressions in interneurons were also downregulated in the deprived barrels, the GFP expression remained unchanged. Patch-clamp recording from spiny cells showed a 1.5-fold reduction of intracortical evoked IPSCs (eIPSCs) in deprived versus spared cortices. The reduction in eIPSCs occurred via changes in presynaptic properties and unitary IPSC amplitudes. Miniature IPSCs showed subtle but significant differences between the two experimental conditions. In addition, properties of the IPSCs in deprived barrels resemble those of IPSCs recorded in immature brains (P7). Together, these results suggest that the properties of local intracortical inhibitory networks are modified by sensory experiences. Perisomatic inhibition mediated by PV-positive basket cells is pruned by sensory deprivation. [ABSTRACT FROM AUTHOR]

The functional organization of the basal ganglia (BG) is often defined according to one of two opposing schemes. The first proposes multiple, essentially independent channels of information processing. The second posits convergence and lateral integration of striatal channels at the level of the globus pallidus (GP). We tested the hypothesis that these proposed aspects of functional connectivity within the striatopallidal axis are dynamic and related to brain state. Local field potentials (LFPs) were simultaneously recorded from multiple sites in striatum and GP in anesthetized rats during slow-wave activity (SWA) and during global activation evoked by sensory stimulation. Functional connectivity was inferred from comparative analyses of the internuclear and intranuclear coherence between bipolar derivations of LFPs. During prominent SWA, as shown in the electrocorticogram and local field potentials in the basal ganglia, intranuclear coherence, and, thus, lateral functional connectivity within striatum or globus pallidus was relatively weak. Furthermore, the temporal coupling of LFPs recorded across these two nuclei involved functional convergence at the level of GP. Global activation, indicated by a loss of SWA, was accompanied by a rapid functional reorganization of the striatopallidal axis. Prominent lateral functional connectivity developed within GP and, to a significantly more constrained spatial extent, striatum. Additionally, functional convergence on GP was no longer apparent, despite increased internuclear coherence. These data demonstrate that functional connectivity within the BG is highly dynamic and suggest that the relative expression of organizational principles, such as parallel, independent processing channels, striatopallidal convergence, and lateral integration within BG nuclei, is dependent on brain state. [ABSTRACT FROM AUTHOR]

State-dependent EEG in the hippocampus (HPC) has traditionally been divided into two activity patterns: theta, a large-amplitude, regular oscillation with a bandwidth of 3-12 Hz, and large-amplitude irregular activity (LIA), a less regular signal with broadband characteristics. Both of these activity patterns have been linked to the memory functions subserved by the HPC. Here we describe, using extracellular field recording techniques in naturally sleeping and urethane-anesthetized rats, a novel state present during deactivated stages of sleep and anesthesia that is characterized by a prominent large-amplitude and slow frequency (≤1 Hz) rhythm. We have called this activity the hippocampal slow oscillation (SO) because of its similarity and correspondence with the previously described neocortical SO. Almost all hippocampal units recorded exhibited differential spiking behavior during the SO as compared with other states. Although the hippocampal SO occurred in situations similar to the neocortical SO, it demonstrated some independence in its initiation, coordination, and coherence. The SO was abolished by sensory stimulation or cholinergic agonism and was enhanced by increasing anesthetic depth or muscarinic receptor antagonism. Laminar profile analyses of the SO showed a phase shift and prominent current sink-source alternations in stratum lacunosum-moleculare of CA1. This, along with correlated slow oscillatory field and multiunit activity in superficial entorhinal cortex suggests that the hippocampal SO may be coordinated with slow neocortical activity through input arriving via the temporo-ammonic pathway. This novel state may present a favorable milieu for synchronization-dependent synaptic plasticity within and between hippocampal and neocortical ensembles. [ABSTRACT FROM AUTHOR]

Use-dependent modifications of synapses have been well described in the developing visual cortex, but the ability for experience to modify synapses in the adult visual cortex is poorly understood. We found that 10 d of late-onset visual deprivation modifies both presynaptic and postsynaptic elements at the layer 4→2/3 connection in the visual cortex of adult mice, and these changes differ from those observed in juveniles. Although visual deprivation in juvenile mice modifies the subunit composition and increases the current duration of synaptic NMDA receptors (NMDARs), no such effect is observed at synapses between layer 4 and layer 2/3 pyramidal neurons in adult mice. Surprisingly, visual deprivation in adult mice enhances the temporal summation of NMDAR-mediated currents induced by bursts of high-frequency stimulation. The enhanced temporal summation of NMDAR-mediated currents in deprived cortex could not be explained by a reduction in the rate of synaptic depression, because our data indicate that late-onset visual deprivation actually increases the rate of synaptic depression. Biochemical and electrophysiological evidence instead suggest that the enhanced temporal summation in adult mice could be accounted for by a change in the molecular composition of NMDARs at perisynaptic/extrasynaptic sites. Our data demonstrate that the experience-dependent modifications observed in the adult visual cortex are different from those observed during development. These differences may help to explain the unique consequences of sensory deprivation on plasticity in the developing versus mature cortex. [ABSTRACT FROM AUTHOR]

Acquisition and performance of instrumental actions are assumed to require both action--outcome and stimulus-response (S-R) habit processes. Over the course of extended training, control over instrumental performance shifts from goal-directed action-outcome associations to S-R associations that progressively gain domination over behavior. Lesions of the lateral part of the dorsal striatum disrupt this process, and rats with lesions to the lateral striatum showed selective sensitivity to devaluation of the instrumental outcome (Yin et al., 2004), indicating that this area is necessary for habit formation. The present experiment further explored the basis of this dysfunction by examining the ability of rats subjected to bilateral 6-hydroxydopamine lesions of the nigrostriatal dopaminergic pathway to develop behavioral autonomy with overtraining. Rats were given extended training on two cued instrumental tasks associating a stimulus (a tone or a light) with an instrumental action (lever press or chain pull) and a food reward (pellets or sucrose). Both tasks were run daily in separate sessions. Overtraining was followed by a test of goal sensitivity by satiety-specific devaluation of the reward. In control animals, one action (lever press) was insensitive to reward devaluation, indicating that it became a habit, whereas the second action (chain pull) was still sensitive to goal devaluation. This result provides evidence that the development of habit learning may depend on the characteristics of the response. In dopamine-depleted rats, lever press and chain pull remained sensitive to reward devaluation, evidencing a role of striatal dopamine transmission in habit formation. [ABSTRACT FROM AUTHOR]

We investigated how V1 neurons integrate two stimulus features by presenting stimuli from a stimulus set made up of all combinations of eight different directions of motion and nine binocular disparities. We investigated the occurrence and shape of the resulting joint tuning function. Among V1 neurons, ∼ 80% were jointly tuned for disparity with orientation or direction. The joint tuning function of all jointly tuned neurons was separable into distinct tuning for disparity on the one hand, and orientation or direction tuning on the other. The degree of separability and the mutual information between the stimulus and the firing rates were strongly correlated. The mutual information of jointly tuned neurons when both features were decoded together was highly correlated with the mutual information when the two features were decoded separately, and the information was then summed. Jointly tuned neurons were just as good at representing information about single features as neurons tuned for only a single feature. The tuning properties of most jointly tuned neurons did not dynamically evolve over time, nor did jointly tuned neurons respond earlier than neurons tuned for only a single feature. The response selectivity of V1 neurons is low and decreases the information that a neuron represents about a stimulus. Together these results suggest that distinct stimulus features are integrated very early in visual processing. Furthermore, V1 generates a distributed representation through low response selectivity that avoids the curse of dimensionality by using separable joint tuning functions. [ABSTRACT FROM AUTHOR]