Charles D. Gilbert

Significance: Perceptual learning is a form of memory involving improvement in the ability to detect or discriminate between sensory stimuli. Encoding learned information requires plasticity of cortical circuits. Physiological studies have suggested that even the earliest stages in sensory cortical processing show functional changes associated with perceptual improvements. Previously, we have shown experience-dependent change in cortical circuits associated with retinal lesions that can account for functional adaptation to CNS lesions. Here, we have studied whether these changes are also associated with normal visual experience, specifically with perceptual learning. We found that during the course of perceptual learning axon collaterals in primary visual cortex (V1) undergo sprouting and pruning, suggesting how V1 is engaged in encoding learned information.

Significance: One of the fundamental tasks of vision is to group the image elements that belong to one object and to segregate them from other objects and the background. Such a process, known as contour integration, is thought of as involving both long-range horizontal connections in the primary visual cortex (V1) and feedback influences from higher cortical areas such as V4. Using conditional Granger causality analysis of simultaneously recorded neurons in monkey visual cortical areas V1 and V4, we are able to dissect the respective contributions of intraareal and interareal interactions during contour integration, indicating that feedback and lateral connections work synergistically to group and segment visual image components.

Significance: Amyloid precursor protein (APP) has long been implicated in Alzheimer’s disease, but its normal physiological role has only recently come to light. Here we demonstrate that APP plays a key role in axonal pruning after experience-dependent plasticity in the adult. Furthermore, we show that APP operates in a cell-autonomous fashion in the cortex to induce axonal pruning after sensory loss. APP is therefore important for the normal process of adult cortical plasticity through its role in the sculpting of axonal arbors.

The functional architecture of adult cerebral cortex retains a capacity for experience-dependent change. This is seen after focal binocular lesions as rapid changes in receptive field (RF) of the lesion projection zone (LPZ) in the primary visual cortex (V1). To study the dynamics of the circuitry underlying these changes longitudinally, we implanted microelectrode arrays in macaque (Macaca mulatta) V1, eliminating the possibility of sampling bias, which was a concern in previous studies. With this method, we observed a rapid initial recovery in the LPZ and, during the following weeks, 63–89% of the sites in the LPZ showed recovery of visual responses with significant position tuning. The RFs shifted ∼3° away from the scotoma. In the absence of a lesion, visual stimulation surrounding an artificial scotoma did not elicit visual responses, suggesting that the postlesion RF shifts resulted from cortical reorganization. Interestingly, although both spikes and LFPs gave consistent prelesion position tuning, only spikes reflected the postlesion remapping.

The functional properties of adult cortical neurons are subject to alterations in sensory experience. Retinal lesions lead to remapping of cortical topography in the region of primary visual cortex representing the lesioned part of the retina, the lesion projection zone (LPZ), with receptive fields shifting to the intact parts of the retina. Neurons within the LPZ receive strengthened input from the surrounding region by growth of the plexus of excitatory long-range horizontal connections. Here, by combining cell type-specific labeling with a genetically engineered recombinant adeno-associated virus andin vivotwo-photon microscopy in adult macaques, we showed that the remapping was also associated with alterations in the axonal arbors of inhibitory neurons, which underwent a parallel process of pruning and growth. The axons of inhibitory neurons located within the LPZ extended across the LPZ border, suggesting a mechanism by which new excitatory input arising from the peri-LPZ is balanced by reciprocal inhibition arising from the LPZ.

Significance: Perceptual grouping links line segments that define object contours and distinguishes them from background contours. This process is reflected in the responses to contours of neurons in primary visual cortex (V1), and depends on long-range horizontal cortical connections. We present a network model, based on an interaction between recurrent inputs to V1 and intrinsic connections within V1, which accounts for task-dependent changes in the properties of V1 neurons. The model simulates top-down modulation of effective connectivity of intrinsic cortical connections among biophysically realistic neurons. It quantitatively reproduces the magnitude and time course of the facilitation of V1 neuronal responses to contours.

Sensory experience alters cortical circuitry by parallel processes of axon outgrowth and pruning, but the mechanisms that control these rearrangements are poorly understood. Usingin vivo2-photon longitudinal imaging, we found a marked reduction in axonal pruning in somatosensory cortex of mice with a knock-out of theDR6gene, which codes for Death Receptor 6. This effect was seen for both long-range horizontal excitatory connections and for the axons of inhibitory neurons. These results identify a new pathway governing axonal plasticity associated with experience-dependent changes in cortical maps.

In contrast to the traditional idea that the processing of visual information consists of a sequence of feedforward operations, with neuronal functional properties taking on increasing complexity as the information progresses through a hierarchy of cortical areas, increasing evidence points towards a reverse process, with higher-order cognitive influences interacting with information coming from the retina. Thus, rather than having a fixed functional role, neurons should be thought of as adaptive processors, changing their function according to the behavioural context. Vision is an active process in which higher-order cognitive influences affect the operations performed by cortical neurons. Visual pathways operate bidirectionally, with each feedforward connection being matched by feedback or re-entrant connections going from higher- to lower-order cortical areas. Top-down influences include various forms of attention, such as spatial, object oriented and feature oriented attention. Top-down influences are not limited to attention but mediate a much broader range of functional roles, including perceptual task, object expectation, scene segmentation, efference copy, working memory and the encoding and recall of learned information. The effect of top-down influences is to change the information conveyed by neurons, both by altering the tuning of their responses to stimulus attributes and by changing the structure of correlations over neuronal ensembles. All areas of the visual pathway, except for the retina, are subject to top-down influences, including early cortical stages of visual processing such as the primary visual cortex and the lateral geniculate nucleus, and all areas along the dorsal and ventral visual cortical pathways. Each area contains an association field of potential interactions, and expresses a subset of these interactions to execute different functions. The sources of top-down influences are widespread, with each area providing information reflecting the functional properties of that area. As a consequence, even a single neuron can be viewed as a microcosm of activity occurring throughout the visual pathway. We propose that the circuit mechanism of top-down control and adaptive processing involves a gating of intrinsic cortical circuits within an area mediated by long-range feedback connections to that area. By selecting a subset of inputs, a neuron can express different components of its association field, and as a result take on different functional roles.

The primary visual cortex (V1) changes its computation according to the perceptual task being performed. We propose that this cognitive modulation results from gating of V1 intrinsic connections. To test this idea, using behavioral paradigms that engage top-down modulation of V1 contextual interactions, we recorded from chronically implanted electrode arrays in macaques. We observed task-dependent changes in interactions between V1 sites measured both by correlation between spike trains and by coherence between local field potentials (LFP-LFP coherence). The direction of the changes in aggregate activity, as measured by LFPs, depended on perceptual strategy: perceptual grouping increased LFP coherence between sites crucial for the task, whereas perceptual segregation lowered the LFP coherence. Using spiking activity as a measure, we found that the behaviorally driven changes in correlation structure between neurons dramatically increased the stimulus-related information that they convey; this additional increase in encoded information at the level of neuronal ensembles equals that obtained from task-driven reconfigurations of neural tuning curves. The improvements in information encoding were strongest for stimuli with greatest discrimination difficulty.