Dynamic population coding in primary visual cortex

More than a century ago Ramon y Cajal pioneered the description of neural circuits. Currently, new techniques are being developed to streamline the characterization of entire neural circuits. Even if this 'connectome' approach is successful, it will represent only a static description of neural circuits. Thus, a fundamental question in neuroscience is to understand how information is dynamically represented by neural populations. In this thesis, I studied two main aspects of dynamical population codes. ^ First, I studied how the exposure or adaptation, for a fraction of a second to oriented gratings dynamically changes the population response of primary visual cortex neurons. The effects of adaptation to oriented gratings have been extensively explored in psychophysical and electrophysiological experiments. However, whether rapid adaptation might induce a change in the primary visual cortex's functional connectivity to dynamically impact the population coding accuracy is currently unknown. To address this issue, we performed multi-electrode recordings in primary visual cortex, where adaptation has been previously shown to induce changes in the selectivity and response amplitude of individual neurons. We found that adaptation improves the population coding accuracy. The improvement was more prominent for iso- and orthogonal orientation adaptation, consistent with previously reported psychophysical experiments. We propose that selective decorrelation is a metabolically inexpensive mechanism that the visual system employs to dynamically adapt the neural responses to the statistics of the input stimuli to improve coding efficiency. ^ Second, I investigated how ongoing activity modulates orientation coding in single neurons, neural populations and behavior. Cortical networks are never silent even in the absence of external stimulation. The ongoing activity can account for up to 80% of the metabolic energy consumed by the brain. Thus, a fundamental question is to understand the functional role of ongoing activity and its impact on neural computations. I studied how the orientation coding by individual neurons and cell populations in primary visual cortex depend on the spontaneous activity before stimulus presentation. We hypothesized that since the ongoing activity of nearby neurons is strongly correlated, it would influence the ability of the entire population of orientation-selective cells to process orientation depending on the prestimulus spontaneous state. Our findings demonstrate that ongoing activity dynamically filters incoming stimuli to shape the accuracy of orientation coding by individual neurons and cell populations and this interaction affects behavioral performance. In summary, this thesis is a contribution to the study of how dynamic internal states such as rapid adaptation and ongoing activity modulate the population code accuracy. ^

Learning reward timing in cortex through reward dependent expression of synaptic plasticity.

The ability to represent time is an essential component of cognition but its neural basis is unknown. Although extensively studied both behaviorally and electrophysiologically, a general theoretical framework describing the elementary neural mechanisms used by the brain to learn temporal representations is lacking. It is commonly believed that the underlying cellular mechanisms reside in high order cortical regions but recent studies show sustained neural activity in primary sensory cortices that can represent the timing of expected reward. Here, we show that local cortical networks can learn temporal representations through a simple framework predicated on reward dependent expression of synaptic plasticity. We assert that temporal representations are stored in the lateral synaptic connections between neurons and demonstrate that reward-modulated plasticity is sufficient to learn these representations. We implement our model numerically to explain reward-time learning in the primary visual cortex (V1), demonstrate experimental support, and suggest additional experimentally verifiable predictions.

Organization of the inferotemporal cortex in the macaque monkey: Connections of areas PITv and CITvp

Visual cortex of macaque monkeys consists of a large number of cortical areas that span the occipital, parietal, temporal, and frontal lobes and occupy more than half of cortical surface. Although considerable progress has been made in understanding the contributions of many occipital areas to visual perceptual processing, much less is known concerning the specific functional contributions of higher areas in the temporal and frontal lobes. Previous behavioral and electrophysiological investigations have demonstrated that the inferotemporal cortex (IT) is essential to the animal's ability to recognize and remember visual objects. While it is generally recognized that IT consists of a number of anatomically and functionally distinct visual-processing areas, there remains considerable controversy concerning the precise number, size, and location of these areas. Therefore, the precise delineation of the cortical subdivisions of inferotemporal cortex is critical for any significant progress in the understanding of the specific contributions of inferotemporal areas to visual processing. In this study, anterograde and/or retrograde neuroanatomical tracers were injected into two visual areas in the ventral posterior and central portions of IT (areas PITv and CITvp) to elucidate the corticocortical connections of these areas with well known areas of occipital cortex and with less well understood regions of inferotemporal cortex. The locations of injection sites and the delineation of the borders of many occipital areas were aided by the pattern of interhemispheric connections, revealed following callosal transection and subsequent labeling with HRP. The resultant patterns of connections were represented on two-dimensional computational (CARET) and manual cortical maps and the laminar characteristics and density of the projection fields were quantified. The laminar and density features of these corticocortical connections demonstrate thirteen anatomically distinct subdivisions or areas distributed within the superior temporal sulcus and across the inferotemporal gyrus. These results serve to refine previous descriptions of inferotemporal areas, validate recently identified areas, and provide a new description of the hierarchical relationships among occipitotemporal cortical areas in macaques. ^

Organization of hue selectivity in macaque V2 thin stripes.

V2 has long been recognized to contain functionally distinguishable compartments that are correlated with the stripelike pattern of cytochrome oxidase activity. Early electrophysiological studies suggested that color, direction/disparity, and orientation selectivity were largely segregated in the thin, thick, and interstripes, respectively. Subsequent studies revealed a greater degree of homogeneity in the distribution of response properties across stripes, yet color-selective cells were still found to be most prevalent in the thin stripes. Optical recording studies have demonstrated that thin stripes contain both color-preferring and luminance-preferring modules. These thin stripe color-preferring modules contain spatially organized hue maps, whereas the luminance-preferring modules contain spatially organized luminance-change maps. In this study, the neuronal basis of these hue maps was determined by characterizing the selectivity of neurons for isoluminant hues in multiple penetrations within previously characterized V2 thin stripe hue maps. The results indicate that neurons within the superficial layers of V2 thin stripe hue maps are organized into columns whose aggregated hue selectivity is closely related to the hue selectivity of the optically defined hue maps. These data suggest that thin stripes contain hue maps not simply because of their moderate percentage of hue-selective neurons, but because of the columnar and tangential organization of hue selectivity.

Recovery from monocular deprivation using binocular deprivation.

Ocular dominance (OD) plasticity is a robust paradigm for examining the functional consequences of synaptic plasticity. Previous experimental and theoretical results have shown that OD plasticity can be accounted for by known synaptic plasticity mechanisms, using the assumption that deprivation by lid suture eliminates spatial structure in the deprived channel. Here we show that in the mouse, recovery from monocular lid suture can be obtained by subsequent binocular lid suture but not by dark rearing. This poses a significant challenge to previous theoretical results. We therefore performed simulations with a natural input environment appropriate for mouse visual cortex. In contrast to previous work, we assume that lid suture causes degradation but not elimination of spatial structure, whereas dark rearing produces elimination of spatial structure. We present experimental evidence that supports this assumption, measuring responses through sutured lids in the mouse. The change in assumptions about the input environment is sufficient to account for new experimental observations, while still accounting for previous experimental results.

POPULATION CODING IN LAMINAR CORTICAL CIRCUITS

One of the fundamental questions in neuroscience is to understand how encoding of sensory inputs is distributed across neuronal networks in cerebral cortex to influence sensory processing and behavioral performance. The fact that the structure of neuronal networks is organized according to cortical layers raises the possibility that sensory information could be processed differently in distinct layers. The goal of my thesis research is to understand how laminar circuits encode information in their population activity, how the properties of the population code adapt to changes in visual input, and how population coding influences behavioral performance. To this end, we performed a series of novel experiments to investigate how sensory information in the primary visual cortex (V1) emerges across laminar cortical circuits. First, it is commonly known that the amount of information encoded by cortical circuits depends critically on whether or not nearby neurons exhibit correlations. We examined correlated variability in V1 circuits from a laminar-specific perspective and observed that cells in the input layer, which have only local projections, encode incoming stimuli optimally by exhibiting low correlated variability. In contrast, output layers, which send projections to other cortical and subcortical areas, encode information suboptimally by exhibiting large correlations. These results argue that neuronal populations in different cortical layers play different roles in network computations. Secondly, a fundamental feature of cortical neurons is their ability to adapt to changes in incoming stimuli. Understanding how adaptation emerges across cortical layers to influence information processing is vital for understanding efficient sensory coding. We examined the effects of adaptation, on the time-scale of a visual fixation, on network synchronization across laminar circuits. Specific to the superficial layers, we observed an increase in gamma-band (30-80 Hz) synchronization after adaptation that was correlated with an improvement in neuronal orientation discrimination performance. Thus, synchronization enhances sensory coding to optimize network processing across laminar circuits. Finally, we tested the hypothesis that individual neurons and local populations synchronize their activity in real-time to communicate information about incoming stimuli, and that the degree of synchronization influences behavioral performance. These analyses assessed for the first time the relationship between changes in laminar cortical networks involved in stimulus processing and behavioral performance.

Effects of early and late lesion of orbital frontal cortex on visual processing of faces in rhesus macaques (Macaca mulatta)

Many mental disorders disrupt social skills, yet few studies have examined how the brain processes social information. Functional neuroimaging, neuroconnectivity and electrophysiological studies suggest that orbital frontal cortex plays important roles in social cognition, including the analysis of information from faces, which are important cues in social interactions. Studies in humans and non-human primates show that damage to orbital frontal cortex produces social behavior impairments, including abnormal aggression, but these studies have failed to determine whether damage to this area impairs face processing. In addition, it is not known whether damage early in life is more detrimental than damage in adulthood. This study examined whether orbital frontal cortex is necessary for the discrimination of face identity and facial expressions, and for appropriate behavioral responses to aggressive (threatening) facial expressions. Rhesus monkeys (Macaca mulatta) received selective lesions of orbital frontal cortex as newborns or adults. As adults, these animals were compared with sham-operated controls on their ability to discriminate between faces of individual monkeys and between different facial expressions of emotion. A passive visual paired-comparison task with standardized rhesus monkey face stimuli was designed and used to assess discrimination. In addition, looking behavior toward aggressive expressions was assessed and compared with that of normal control animals. The results showed that lesion of orbital frontal cortex (1) may impair discrimination between faces of individual monkeys, (2) does not impair facial expression discrimination, and (3) changes the amount of time spent looking at aggressive (threatening) facial expressions depending on the context. The effects of early and late lesions did not differ. Thus, orbital frontal cortex appears to be part of the neural circuitry for recognizing individuals and for modulating the response to aggression in faces, and the plasticity of the immature brain does not allow for recovery of these functions when the damage occurs early in life. This study opens new avenues for the assessment of rhesus monkey face processing and the neural basis of social cognition, and allows a better understanding of the nature of the neuropathology in patients with mental disorders that disrupt social behavior, such as autism. ^

Modular organization of the cortical connections linking visual areas V1, V2 and V4 in Macaque monkeys

The macaque cortical visual system is hierarchically organized into two streams, the ventral stream for recognizing objects and the dorsal stream for analyzing spatial relationships. The ventral stream extends from striate cortex or area V1 to inferior temporal cortex (IT) through extra-striate areas V2 and V4. Between V1 and V2, the ventral stream consists of two roughly parallel sub-streams, one extending from the cytochrome oxidase (CO) rich blobs in V1 to the CO rich thin stripes in V2, the other extending from the interblobs in V1 to interstripes, in V2. The blob-dominated sub-stream is thought to analyze the surface features such as color, whereas the interblob-dominated one is thought to analyze the contour features such as shape. ^ In the current study, the organization of cortical pathways linking V2 thin stripe and interstripe compartments with area V4 was investigated using a combination of physiological and anatomical techniques. Different compartments of V2 were first characterized, in vivo, using optical recording of intrinsic cortical signals. These functionally derived maps of V2 stripe compartments were then used to guide iontophoretic injections of multiple, distinguishable, anterograde tracers into specific V2 compartments. The distribution of labeled axons was analyzed either in horizontal sections through the prelunate gyrus, or in tangentially sectioned portions of physically unfolded cortex containing the lunate sulcus, prelunate gyrus and superior temporal sulcus. When a V2 thin stripe and adjacent interstripe were injected with distinguishable tracers, a large primary and several secondary foci were observed in V4. The primary focus from the thin stripe injection was spatially segregated from the primary focus from the V2 interstripe injection, suggesting a retention of the pattern of compartmentation. ^ We examined the distribution of retrogradely labeled cells in V1 following the injections of tracers into V2 different compartments, in order to quantitate just how parallel the two sub-streams are from V1 to V2. Our results suggest that both blobs and interblobs project to thin stripes in V2, whereas only interblobs project to interstripes. This asymmetrical segregation argues against the original proposal of strict parallelism. (Abstract shortened by UMI.) ^

The contributions of the hippocampal formation, perirhinal cortex and areas TH/TF to object, spatial and contextual recognition memory in primates

Adult monkeys (Macaca mulatta) with lesions of the hippocampal formation, perirhinal cortex, areas TH/TF, as well as controls were tested on tasks of object, spatial and contextual recognition memory. ^ Using a visual paired-comparison (VPC) task, all experimental groups showed a lack of object recognition relative to controls, although this impairment emerged at 10 sec with perirhinal lesions, 30 sec with areas TH/TF lesions and 60 sec with hippocampal lesions. In contrast, only perirhinal lesions impaired performance on delayed nonmatching-to-sample (DNMS), another task of object recognition memory. All groups were tested on DNMS with distraction (dDNMS) to examine whether the use of active cognitive strategies during the delay period could enable good performance on DNMS in spite of impaired recognition memory (revealed by the VPC task). Distractors affected performance of animals with perirhinal lesions at the 10-sec delay (the only delay in which their DNMS performance was above chance). They did not affect performance of animals with areas TH/TF lesions. Hippocampectomized animals were impaired at the 600-sec delay (the only delay at which prevention of active strategies would likely affect their behavior). ^ While lesions of areas TH/TF impaired spatial location memory and object-in-place memory, hippocampal lesions impaired only object-in-place memory. The pattern of results for perirhinal cortex lesions on the different task conditions indicated that this cortical area is not critical for spatial memory. ^ Finally, all three lesions impaired contextual recognition memory processes. The pattern of impairment appeared to result from the formation of only a global representation of the object and background, and suggests that all three areas are recruited for associating information across sources. ^ These results support the view that (1) the perirhinal cortex maintains storage of information about object and the context in which it is learned for a brief period of time, (2) areas TH/TF maintain information about spatial location and form associations between objects and their spatial relationship (a process that likely requires additional time) and (3) the hippocampal formation mediates associations between objects, their spatial relationship and the general context in which these associations are formed (an integrative function that requires additional time). ^