The question of how shape is represented is of central interest to understanding visual processing in cortex. While tuning properties of the cells in early part of the ventral visual stream, thought to be responsible for object recognition in the primate, are comparatively well understood, several different theories have been proposed regarding tuning in higher visual areas, such as V4. We used the model of object recognition in cortex presented by Riesenhuber and Poggio (1999), where more complex shape tuning in higher layers is the result of combining afferent inputs tuned to simpler features, and compared the tuning properties of model units in intermediate layers to those of V4 neurons from the literature. In particular, we investigated the issue of shape representation in visual area V1 and V4 using oriented bars and various types of gratings (polar, hyperbolic, and Cartesian), as used in several physiology experiments. Our computational model was able to reproduce several physiological findings, such as the broadening distribution of the orientation bandwidths and the emergence of a bias toward non-Cartesian stimuli. Interestingly, the simulation results suggest that some V4 neurons receive input from afferents with spatially separated receptive fields, leading to experimentally testable predictions. However, the simulations also show that the stimulus set of Cartesian and non-Cartesian gratings is not sufficiently complex to probe shape tuning in higher areas, necessitating the use of more complex stimulus sets.

<p>The visual system is thought to represent the trajectory of moving objects in the activity of large populations of cortical neurons that respond preferentially to the direction of stimulus motion. Here I employed in vivo voltage sensitive dye (VSD) imaging to explore how abrupt changes in the trajectory of a moving stimulus impact the population coding of motion direction in ferret primary visual cortex (V1). For motion in a constant direction, the peak of the cortical population response reliably signaled the stimulus trajectory; but for abrupt changes in motion direction, the peak of the population response departed significantly from the stimulus trajectory in a fashion that depended on the size of the direction deviation. For small direction deviation angles, the peak of the active population shifted from values consistent with the initial direction of motion to those consistent with the final direction of motion by progressing smoothly through intermediate directions not present in the stimulus. In contrast, for large direction deviation angles, peak values consistent with the initial motion direction were followed by: a small deviation away from the final motion direction, a rapid 180° jump, and a gradual shift to the final direction. These departures of the population response from the actual trajectory of the stimulus predict specific misperceptions of motion direction that were confirmed by human psychophysical experiments. I conclude that cortical dynamics and population coding mechanisms combine to place constraints on the accuracy with which abrupt changes in direction of motion can be represented by cortical circuits.</p> / Dissertation

We perceive the world through sensory experience. Sensory information is registered and processed by our brain in a modality specific fashion. Interestingly, studies have shown that the visual cortex of early but not late blind subjects is able to respond to touch or sound (Sadato et al., 1996; Buchel et al., 1998; Weeks et al., 2000; Gougoux et al., 2009). Here, we investigated whether sensory parcellation in adult cortex is innate or is acquired during early postnatal life in an experience-dependent manner. Furthermore, we studied the anatomical substrates and molecular pathways possibly involved in cross-modal activation and its plasticity. First, mice were reared from birth in total darkness until adulthood (DR) to replicate the human blind condition. Cross-modal activity and the underlying circuitry were analyzed. We found that DR visual cortex was strongly activated by sound stimulation using functional imaging, single-unit recording, and c-Fos immunohistochemistry. Functional analysis was followed by anatomical tracing studies, which showed ectopic projections from the auditory thalamus and auditory cortex into the secondary visual area in DR animals. The second half of our study looked at how visual experience affects cross-modal plasticity. We found that cross-modal activity and ectopic connectivity is present in normally reared young mice (25 postnatal days: P25). Normal sensory experience through the first two months of postnatal life was sufficient to decrease the number of ectopic inputs. Interestingly, exposing DR mice to visual experience as adults established transient functional sensory specificity in the visual cortex without eliminating the ectopic anatomical inputs. Lastly, we tested several molecular pathways that can potentially regulate cross-modal plasticity. We found that myelin signaling and cholinergic modulation controls the duration of cross-modal plasticity and consolidates sensory modularization. Overall, our work proposes a model of how cross-modal inputs into early sensory areas are pruned or retained depending on early life experience. This study provides insight into how the cortex develops functional specificity, and help approach disorders that exhibit abnormal sensory integration and disrupted neuronal connectivity such as Autism Spectrum Disorder.

The mammalian brain is a complex computing system that contains billions of neurons and trillions of connections. Is there a general principle that governs the processing in such large neural populations? This dissertation attempts to address this question using computational modeling and quantitative analysis of direct physiological measurements of large neural populations in the monkey primary visual cortex (V1). First, the complete spatiotemporal dynamics of V1 responses over the entire region that is activated by small stationary stimuli are characterized quantitatively. The dynamics of the responses are found to be systematic but complex. Importantly, they are inconsistent with many popular computational models of neural processing. Second, a simple population gain control (PGC) model that can account for these complex response properties is proposed for the small stationary stimuli. The PGC model is then used to predict the responses to stimuli composed of two elements and stimuli that move at a constant speed. The predictions of the model are consistent with the measured responses in V1 for both stimuli. PGC is the first model that can account for the complete spatiotemporal dynamics of V1 population responses for different types of stimuli, suggesting that gain control is a general mechanism of neural processing. / text

Οι περισσότερες πληροφορίες που αφορούν μοριακούς μηχανισμούς πλαστικότητας στο κεντρικό νευρικό σύστημα, πηγάζουν από μελέτες συγκεκριμένων τύπων μακρόχρονης ενδυνάμωσης (LTP) και μακρόχρονης αναστολής (LTD), οι οποίοι εξαρτώνται από την ενεργότητα των υποδοχέων N-methyl-D-aspartate (NMDA) του γλουταμινικού οξέος. Αλλαγές στην φωσφορυλίωση των υποδοχέων NMDA από διάφορες κινάσες και φωσφατάσες διαμεσολαβούν ή και ρυθμίζουν την έκφραση του LTP και του LTD. Η οπτική αποστέρηση, όπως η εκτροφή πειραματόζωων στο σκοτάδι, επιμηκύνει την κρίσιμη περίοδο πλαστικότητας του οπτικού φλοιού. Οι υποδοχείς NMDA του γλουταμινικού οξέος, έχει αποδειχθεί ότι εμπλέκονται σημαντικά στην πλαστικότητα του οπτικού φλοιού. Η φωσφορυλίωση τους εμπλέκεται στη συναπτική πλαστικότητα μέσω της ρύθμισης της διακίνησης τους στην σύναψη και της έκφρασης τους στη επιφάνεια του κυττάρου, καθώς και μέσω της επίδρασης στη λειτουργία του ιοντικού διαύλου του υποδοχέα. Η σερίνη 1303 της υπομονάδας NR2B των υποδοχέων NMDA αποτελεί την κύρια περιοχή φωσφορυλίωσης από την CaM κινάση II και την PKC. Σκοπός της παρούσας μελέτης είναι η συσχέτιση των μεταβολών του υποδοχέα NMDA, ο οποίος συμμετέχει σε φαινόμενα πλαστικότητας του εγκεφάλου, με την ευαίσθητη περίοδο καθορισμού της αρχιτεκτονικής του οπτικού φλοιού. Για το σκοπό αυτό εξετάσαμε τις μεταβολές της φωσφορυλίωσης της υπομονάδας NR2B των υποδοχέων NMDA σε επίμυες μετά από οπτική αποστέρηση για την περίοδο Ρ0-Ρ21 και Ρ0-Ρ30 (Ρ: postnatal day). Τα αποτελέσματα της παρούσας διπλωματικής εργασίας δείχνουν ότι στον οπτικό φλοιό τα επίπεδα της φωσφορυλίωσης του καταλοίπου σερίνης 1303 της NR2B υπομονάδας των υποδοχέων NMDA αυξήθηκαν στις μεταγεννητικές ημέρες 21 και 30 (κατά 27% και 47% αντίστοιχα) στα πειραματόζωα που υπέστησαν οπτική αποστέρηση συγκριτικά με πειραματόζωα ίδιας ηλικίας των οποίων η εκτροφή πραγματοποιήθηκε σε ημερήσιο κύκλο 12 ώρες φως/ 12 ώρες σκοτάδι. Τα αποτελέσματά μας υποδεικνύουν μια εξαρτώμενη από την εμπειρία ρύθμιση της φωσφορυλίωσης του καταλοίπου σερίνης 1303 της NR2B υπομονάδας των υποδοχέων NMDA . Υπάρχουν ενδείξεις ότι η φωσφωρυλίωση του καταλοίπου ser1303 της υπομονάδας NR2B του υποδοχέα NMDA μέσω της PKC ενισχύει τα NMDA-επαγώμενα ρεύματα (Liao et al., 2001). Επιπλέον μελέτες κατά την ανάπτυξη του οπτικού φλοιού επίμυων και μυών που έχουν υποστεί οπτική αποστέρηση (Carmignoto and Vicini, 1992; Yashiro et al. 2005) έχουν δείξει λειτουργικές μεταβολές του υποδοχέα NMDA και συγκεκριμένα ενίσχυση της διάρκειας του NMDA-επαγώμενου ρεύματος Τα αποτελέσματα της παρούσας μελέτης προτείνουν ότι η φωσφορυλίωση της υπομονάδας NR2B του υποδοχέα NMDA μπορεί να είναι ένας από τους μοριακούς μηχανισμούς οι οποίοι ενέχονται στην λειτουργική μεταβολή του υποδοχέα NMDA, η οποία παρατηρείται κατά την ανάπτυξη του οπτικού φλοιού που έχουν υποστεί οπτική αποστέρηση. Τέλος, τα αποτελέσματα αυτά συμφωνούν και συμπληρώνουν την υπάρχουσα βιβλιογραφία που υποστηρίζει ότι η φωσφορυλίωση αποτελεί έναν από τους παράγοντες που συμβάλλουν στην πλαστικότητα. / Phosphorylation of ligand-gated ion channels is recognized as a potentially important mechanism for short and long-term modulation of ion-channel function. Ionotropic glutamate receptors mediate most excitatory neuronal transmission in the brain and play essential roles in the regulation of synaptic activity. Depending on their specific response to different pharmacological agents, ionotropic glutamate receptors are subdivided into N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors. NMDA receptors are heteromultimers mainly consisting of the obligatory NR1 subunit in combination with NR2A-NR2D and NR3A-B subunits. Many serine/threonine phosphorylation sites have been identified in NMDA receptor subunits, which are substrates for several kinases. Phosphorylation of NMDA receptors mediate synaptic plasticity through regulation of synaptic trafficking and surface expression of these receptors, in addition to the effects on channel function. Phosphorylation on NR2B-Ser1303 is mediated by CaM kinase II and PKC. Visual deprivation has been a powerful tool for investigating the anatomical and physiological correlates of experience-dependent plasticity. Rearing in the dark during a developmentally sensitive period blocks the development of retinal circuitry. In visual cortex, dark-rearing prolongs the critical period for ocular dominance plasticity, reduces LTD and increases LTP, attenuates the maturation of NMDA receptors and attenuates the developmental increase in inhibition relative to excitation. To test the role of neurotransmitter receptor phosphorylation on visual system plasticity, we examined the effects of dark rearing on phosphorylation of NMDA receptor subunit NR2B in rat visual cortex. In visual cortex, we found that dark rearing rats from birth leads to an increase of the percentage of NR2B subunits of the NMDA receptor that are phosphorylated on Serine 1303. Increases in NR2B subunit phosphorylation in dark-reared rats were observed at both P21 (27%) and P30 (47%) which implies that modulation of NMDA subunit phosphorylation appears at the onset and continues during the critical period for ocular dominance plasticity in rats. Our results suggest that NR2B phosphorylation at Ser1303 is regulated by activity in rat visual cortex. There is evidence for PKC-mediated enhancement of NMDA receptor currents by direct phosphorylation of NR2B at Ser1303. Several studies have shown that visual deprivation increases the current duration of synaptic NMDA receptors. A putative molecular basis for this current enhancement could be the increased phosphorylation of NR2B subunit at ser1303.

Object perception is necessary to our understanding of the visual world, yet its neural mechanism remains poorly understood. The goal of this dissertation is to shed light on this mechanism. Current computational models of object perception suggest that regions on opposite sides of a shared border compete, with the winner perceived as the shaped object and the loser as its locally shapeless background (or ground). Recent behavioral work indicates that the result of this competition is suppression of the ground at the level of object shape--a finding not predicted by models. Here, I present three studies that extend this previous research on ground suppression as a mechanism by which object perception is accomplished. I first show that the amount of suppression applied to the ground depends on the amount of competition for object status (Salvagio, Cacciamani, & Peterson, 2012). I then provide the first neural evidence of ground suppression from shape-level competition at both high and low levels of the visual hierarchy, with the latter arising from top-down feedback (Cacciamani, Scalf, & Peterson, submitted). Finally, I show that semantic information pertaining to the ground is accessed prior to the assignment of object status, but unlike shape information, is not suppressed (Cacciamani, Mojica, Sanguinetti, & Peterson, 2014). Together, the three studies that comprise this dissertation demonstrate that ground suppression arising from shape-level competition underlies object perception. This research contradicts traditional theories stating that objects are processed unidirectionally through the visual system in a single feedforward pass; instead, it supports theories of object perception entailing dynamical feedforward and feedback processes.

No description available.

Over the past five decades spatial behavior has been a subject of research interest in psychology and neuroscience, in part based on philosophical theories of mental spatial representations. In order to continue uncovering the facts regarding spatial behavior, the focus of this thesis was on the contribution of entry point and visual inputs to the organization of exploratory locomotion and spatial representation in the rat. Despite the contribution of the hippocampus to spatial abilities, the exploratory locomotion is still visually organized in rats with damage to the hippocampus. On the other hand, recent studies have demonstrated a contribution of visual areas to the spatial ability of the rat. Nevertheless, the contribution of visual cortex to the organization of exploratory locomotion has not been studied in an open field. The experiments in this thesis were designed to characterize the organization of exploratory locomotion to the point of entry and/or visual cues. Rats were started from the edge or center of an open table near or on which a salient object could be placed. The main findings were that rats organized their exploratory locomotion to their point of entry and modified their behavior as they encountered objects. Also, rats with damage to visual cortex displayed an extra-attachment to the visual objects and in contrast to controls did not expand their exploratory locomotion with time. The results are discussed with respect to the centrality of the entry point in the organization of exploratory locomotion and the neural network that control visual exploration in the rat. / xiii, 220 leaves : ill. ; 29 cm. --

Early language experience is thought to be essential to develop a high level of linguistic proficiency in adulthood. Impoverished language input during childhood has been found to lead to functional changes in the brain. In this study, we explored if delayed exposure to a first language modulates the neuroanatomical development of the brain. To do so, voxel-based morphometry (VBM) was carried out in a group of congenitally deaf individuals varying in the age of first exposure to American Sign Language (ASL). To explore a secondary question about the effect of auditory deprivation on structural brain development, a second VBM analysis compared deaf individuals to matched hearing controls. The results show that delayed exposure to sign language is associated with a decrease in grey-matter concentration in the visual cortex close to an area found to show functional reorganization related to delayed exposure to language, while auditory deprivation is associated with a decrease in white matter in the right primary auditory cortex. These findings suggest that a lack of early language experience alters the anatomical organization of the brain.

It has only recently been acknowledged to what large extent the internal dynamics of neural networks could play a role in their function. In this respect, synaptic "noise" -- that is, the influence of the cortical network on single neurons exerted through the massive recurrent circuity that is the hallmark of neocortex -- has recently been shown to have a profound effect on neuronal integrative properties, changing the responses of single neurons across brain states, sometimes within the matter of a few seconds. These internally generated activity states, shaped by and continually shaping the plastic synaptic recurrent connections, then combine with the external inputs to produce a rich repertoire of responses to sensory stimuli in primary cortical regions. In this thesis, we have focused on the {\it spatial} aspect of these internal dynamics, specifically the spatial structure of cortical oscillations, spontaneous and stimulus-evoked. Along the way, we have made an extensive review of the literature concerning propagating waves in thalamus and cortex, and studied network models to investigate how waves depend on network state. We have also introduced new tools for the characterization of spatiotemporal activity patterns in noisy multichannel data. The culmination of this work is a demonstration, using voltage-sensitive dye imaging data taken from the awake monkey, that the population response to a small visual stimulus propagates like a wave across a large extent of primary visual cortex during the awake state, a result contradicting a range of previous studies which seemed to suggest that propagating waves disappear in this case. Moving forward, we have begun to investigate the spatiotemporal structure of local field potential and spiking activity in multielectrode recordings taken from the human and monkey in various states of arousal, to address questions prompted by our initial voltage-sensitive dye imaging study in the monkey. In parallel, we have initiated an analysis of the extent to which neural connectivity can be characterized by the "small-world" effect, the main result of which is that neural graphs may in fact reside outside the small-world regime. The results from these PhD studies thus span the spectrum of scales in neuroscience, from macroscopic activity patterns to microscopic connectivity profiles. It is my sincere hope to expound in these pages a unified theme for these results, and a foundation for further work in neuroscience -- a search for structure within the internal architecture of the system under study.