The vertebrate retina, which provides the visual input to the brain and its main interface with the outside world, is a very attractive model system for approaching the question of the information processing role of biological mechanisms of nerve cells. It is as yet impossible to provide a complete circuit diagram of the retina, but it is now possible to identify a few simple computations that the retina performs and to relate them to specific biophysical mechanisms and circuit elements. In this paper we consider three operations carried out by most retinae: amplification, temporal differentiation, and computation of the direction of motion of visual patterns.

No description available.

A central issue in auditory research is how the auditory brain encodes complex stimuli. However, the process by which the auditory cortex interprets complex sounds during development and the extent to which cortical organization can be manipulated by complex stimulation is still undetermined. We have addressed this gap in the following three studies. First, we characterized the responses of cortical neurons in adult chinchillas to frequency-modulated (FM) stimulation. Next, we asked whether FM coding at the cortical level is innate or if its development is influenced by normal postnatal environmental experience. Finally, we investigated the effect of sustained neonatal FM sweep exposure on the development of cortical responses to tonal and FM stimuli. In our adult study, results indicated that >90% of sampled neurons were responsive to FM sweeps. The population preference was for upward FM sweeps and for medium to fast speeds ( 0.3 kHz/ms). Three types of temporal response patterns were observed: a single peak at sweep onset/offset (‘onset’) and a single peak (‘late’) or multiple peaks (‘burst’) during the sweep. ‘Late’ units expressed the highest direction and speed selectivity; ‘onset’ units were selective only for direction and ‘burst’ units were selective for neither direction nor speed. In our developmental study, our results showed a significant developmental increase in FM direction selectivity. However, FM speed selectivity appeared to be established early in development. In our developmental plasticity study, we hypothesized that constant FM exposure would increase the proportion of auditory neurons that are selectively responsive to the conditioning FM sweep. However, our results showed that while tonal response latencies increased after the exposure period, the conditioning stimulus had minimal effect on the FM direction preferences of cortical neurons and decreased overall neuronal FM speed selectivity. In conclusion, we suggest that chinchilla auditory cortical neurons are not uniquely activated by FM sounds but that FM responses are largely predictable based on how changing frequency stimuli interact with the receptive fields of these neurons. We also propose that the development of FM direction sensitivity is experience-independent and that perhaps normal acoustic experience is required to maintain FM speed tuning.

A central issue in auditory research is how the auditory brain encodes complex stimuli. However, the process by which the auditory cortex interprets complex sounds during development and the extent to which cortical organization can be manipulated by complex stimulation is still undetermined. We have addressed this gap in the following three studies. First, we characterized the responses of cortical neurons in adult chinchillas to frequency-modulated (FM) stimulation. Next, we asked whether FM coding at the cortical level is innate or if its development is influenced by normal postnatal environmental experience. Finally, we investigated the effect of sustained neonatal FM sweep exposure on the development of cortical responses to tonal and FM stimuli. In our adult study, results indicated that >90% of sampled neurons were responsive to FM sweeps. The population preference was for upward FM sweeps and for medium to fast speeds ( 0.3 kHz/ms). Three types of temporal response patterns were observed: a single peak at sweep onset/offset (‘onset’) and a single peak (‘late’) or multiple peaks (‘burst’) during the sweep. ‘Late’ units expressed the highest direction and speed selectivity; ‘onset’ units were selective only for direction and ‘burst’ units were selective for neither direction nor speed. In our developmental study, our results showed a significant developmental increase in FM direction selectivity. However, FM speed selectivity appeared to be established early in development. In our developmental plasticity study, we hypothesized that constant FM exposure would increase the proportion of auditory neurons that are selectively responsive to the conditioning FM sweep. However, our results showed that while tonal response latencies increased after the exposure period, the conditioning stimulus had minimal effect on the FM direction preferences of cortical neurons and decreased overall neuronal FM speed selectivity. In conclusion, we suggest that chinchilla auditory cortical neurons are not uniquely activated by FM sounds but that FM responses are largely predictable based on how changing frequency stimuli interact with the receptive fields of these neurons. We also propose that the development of FM direction sensitivity is experience-independent and that perhaps normal acoustic experience is required to maintain FM speed tuning.

Early experimental work suggested that the retina’s main role was to detect changes in brightness and contrast, namely working as a light detector, and that most of the complex computations in the visual system happened upstream in the brain. In reality, there is a growing wealth of literature indicating that the retina itself processes multiple channels of visual information (contrast, motion, orientation, etc.), making it much more complex than it originally appeared. For instance, there now appear to be over 20 types of retinal ganglion cells. To this end, the work in this thesis will focus on the identification and characterization of a single type of retinal ganglion cell in the mouse retina. In the first section of my results, I will show that this cell type, identified as the only GFP+ ganglion cell in the transgenic Hb9::eGFP retina, is a directionally selective ganglion cell (DSGC), that preferentially responds to objects moving upward through the visual field. This cell has a pronounced morphological asymmetry that helps it to synergistically (along with asymmetric inhibition) generate directionally selective responses. In the second results section, I will describe a novel phenomenon exhibited by Hb9+ DSGCs: Thanks to gap junction mediated signals, Hb9+ cells are able to anticipate moving stimuli and correct for lags that are inherent in visual signals generated by photoreceptors. In the third results section I will elucidate the mechanisms for the gap junction mediated anticipatory signals outlined in the second results section. Together, these results provide a significant advancement in our understanding of how the retina processes moving stimuli and provide a compelling example of how chemical and electrical synapses interact to allow for exquisite signal multiplexing.

<p>The primary visual cortex (V1) is a center in the visual pathway that receives the converging information and sends diverging information to multiple visual areas. It is essential for the normal functioning of the visual system. While processing the input from the outside world, it is also continually modified by the sensory experience. This thesis is dedicated to studying the plasticity in the visual cortex that is associated with experience and brain damage recovery. In this thesis, we discovered that the visual experience induces 5 Hz oscillations that recruit inhibition in V1, sharpening the feature selectivity. We have also demonstrated that gene therapy to convert astrocytes into neurons induces neuronal circuit plasticity and functional recovery in mouse V1 following ischemia.</p>

Natural sound, such as conspecific vocalizations and human speech, represents an important part of the sensory signals animals and humans encounter in their daily lives. This dissertation investigates the neural mechanisms involved in creating response selectivity for complex features of natural acoustic signals and demonstrates that selectivity for spectral motion cues provides a neural mechanism to encode communication signals in the auditory midbrain. Spectral motion is defined as the movement of sound energy upward or downward in frequency at a certain velocity, and is believed to provide the auditory system with an important perceptual cue in the processing of human speech. Using the Mexican free-tailed bat, tadarida brasiliensis, as a model system, this research examined the role of selectivity for spectral motion cues, such as direction and velocity, in creating response selectivity for specific features of the social communication signals emitted by these animals. We show that auditory neurons in the midbrain nucleus of the inferior colliculus (IC) are specifically tuned for the frequency-modulated (FM) direction and velocities found in their conspecific vocalizations. This close agreement between neural tuning and features of natural conspecific signals shows that auditory neurons have evolved to specifically encode features of signals that are vital for the survival of the animal. Furthermore, we find that the neural computations resulting in selectivity for spectral motion are analogous to mechanisms observed in selectivity for visual motion, suggesting the evolution of similar neural mechanisms across sensory modalities. / text

No description available.

Spontaneous travelling waves of neuronal activity are a prominent feature throughout the developing brain and have been shown to be essential for achieving normal function, but the mechanism of their action on post-synaptic connections remains unknown. A well-known and widespread mechanism for altering synaptic strengths is spike-timing dependent plasticity (STDP), whereby the temporal relationship between the pre- and post-synaptic spikes determines whether a synapse is strengthened or weakened. Here, I answer the theoretical question of how these two phenomenon interact: what types of connectivity patterns can emerge when travelling waves drive a downstream area that implements STDP, and what are the critical features of the waves and the plasticity rules that shape these patterns? I then demonstrate how the theory can be applied to the development of the visual system, where retinal waves are hypothesised to play a role in the refinement of downstream connections. My major findings are as follows. (1) Mathematically, STDP translates the correlated activity of travelling waves into coherent patterns of synaptic connectivity; it maps the spatiotemporal structure in waves into a spatial pattern of synaptic strengths, building periodic structures into feedforward circuits. This is analogous to pattern formation in reaction diffusion systems. The theory reveals a role for the wave speed and time scale of the STDP rule in determining the spatial frequency of the connectivity pattern. (2) Simulations verify the theory and extend it from one-dimensional to two-dimensional cases, and from simplified linear wavefronts to more complex realistic and noisy wave patterns. (3) With appropriate constraints, these pattern formation abilities can be harnessed to explain a wide range of developmental phenomena, including how receptive fields (RFs) in the visual system are refined in size and topography and how simple-cell and direction selective RFs can develop. The theory is applied to the visual system here but generalises across different brain areas and STDP rules. The theory makes several predictions that are testable using existing experimental paradigms.

Lorsque les rongeurs explorent leur environnement, ils contactent activement les objets environnants avec leurs vibrisses qui sont ainsi défléchies selon des séquences spatiotemporelles complexes. Le système vibrissal est néanmoins capable d'extraire des informations pertinentes de ces stimulations pour générer un comportement tactile-dépendant. Une question se pose alors: Comment l’information multivibrissale globale est-elle encodée? La représentation corticale des vibrisses au sein du cortex somatosensoriel primaire (S1) du rongeur est dotée de structures anatomiquement remarquables, nommées "tonneaux", au niveau de la couche IV, qui sont organisées de la même manière que les vibrisses sur le museau de l’animal. A chaque "tonneau" correspond une colonne corticale, unité de traitement de l’information, qui reçoit en priorité les informations provenant la vibrisse principale (VP) correspondante. Des enregistrements extracellulaires réalisés dans notre équipe chez le rat ont révélé que les réponses des neurones du cortex S1 et du thalamus sont non seulement sensibles à la direction de déflection locale de leur VP, mais aussi à la direction d'un mouvement global de l’ensemble de leurs vibrisses. Afin de mieux comprendre la manière dont le réseau cortical traite ces scènes tactiles globales, nous avons construit un poste expérimental permettant d’enregistrer en temps réel l’activité du cortex S1 chez la souris par imagerie sensible au potentiel, tout en appliquant des stimuli tactiles complexes à l'aide d'une matrice de 24-stimulateurs vibrissaux. Nous avons de plus développé une méthode permettant d’aligner les données fonctionnelles ainsi obtenues par rapport la carte cytoarchitecturale du réseau cortical sous-jacent. Nous avons ainsi étudié premièrement la distribution spatiale de la sélectivité à la direction de déflection locale d’une vibrisse au niveau d’une colonne corticale. Les réponses aux différentes directions étaient localisées de manière légèrement distincte, autour du centre de la colonne, mais selon une organisation différente de celle précédemment décrite chez le rat. Nous avons montré par la suite que la sélectivité à la direction globale est spatialement organisée dans le cortex "en tonneaux" à l’échelle supra-colonnaire. Les colonnes correspondant aux vibrisses rostrales étant plus sélectives à la direction globale que les colonnes associées aux vibrisses caudales. En outre, les colonnes correspondant aux vibrisses dorsales répondent préférentiellement aux directions globales ventrales, tandis que les colonnes associées aux vibrisses ventrales répondent préférentiellement aux directions globales caudales. Enfin, les réponses induites par des directions globales caudo-ventrales étaient en moyenne les plus fortes pour toutes les colonnes. Nous avons montré que la répartition spatiale de la sélectivité à la direction globale peut être expliquée ni par la saillance prédominante de la position de départ de la séquence de stimulation multivibrissale (effet de bord), ni par la sommation linéaire des réponses aux déflections de quelques vibrisses. Les réponses aux stimulations globales de l'ensemble des vibrisses sont en effet fortement sous-linéaires, indépendamment de la direction de la stimulation. Brièvement, nous montrons ici que sortir de la vision classique du système vibrissal permet une meilleure compréhension de la façon dont les différentes caractéristiques des stimuli complexes sont traitées et de la manière dont les propriétés émergentes du cortex, comme la sélectivité à la direction globale, sont construites. / While rodents explore their environment they actively contact surrounding objects with their array of whiskers, resulting in a complex pattern of multiwhisker deflections. Despite this complexity, the whisker system is able to extract relevant information from the spatiotemporal sequence of deflections to generate touch-dependent behavior. The question that arises is: How is global multiwhisker information encoded? Whiskers are mapped onto layer 4 of the primary somatosensory cortex (S1) as discrete units named “barrels”. Each barrel-related vertical column processes information coming primarily from its corresponding principal whisker (PW). Previous experiments in our lab done with extracellular recordings have revealed that neurons in the rat S1 and thalamus not only show a preferred direction for the local deflection of the PW but also for the direction of a global motion across the whisker pad. To further understand how the cortical network processes global tactile scenes, we built a set-up that enables to perform voltage sensitive dye imaging of the mouse barrel cortex while applying precise tactile stimuli using a 24-multi-whisker stimulator. We further developed a technical method to map the recorded functional data onto the cortical structure. We first studied whether local direction selectivity is spatially distributed within the barrel-related column. Responses to different directions were slightly segregated on space close to the barrel center, but the distribution differed from the one previously described in rat S1, namely a pinwheel-like structure. We then showed that global direction selectivity is spatially organized in the barrel cortex. Columns related to rostral whiskers were more selective to the global direction than columns related to caudal whiskers. Moreover, the columns related to dorsal whiskers preferred ventral global directions, while the columns related to ventral whiskers preferred caudal global directions. Overall the responses to the caudo-ventral global directions were the strongest in average for all the columns. We showed that the spatial distribution of the global direction selectivity can be explained neither by the high salience of the starting position of the deflections on the whiskerpad (a border effect), nor by the linear summation of the responses to deflections of several whiskers. Responses to the global motion of the whisker array are indeed highly sublinear independently of the direction of stimulation. In conclusion, we show here that stepping aside from the classical view of the whisker-to-barrel cortex system allows a better understanding of how different features of complex stimuli are processed and how the emergent properties of the cortex, like the global direction selectivity, are built-up.