A Large-Scale Model of Spatio-Temporal Patterns of Excitation and Inhibition Evoked by the Horizontal Network in Layer 2/3 of the Visual Cortex

Cortical processing of even the most elementary visual stimuli can result in the propagation of information over significant spatiotemporal scales. To fully understand the impact of such phenomena it is essential to consider the influence of both the neural circuitry beyond the immediate retinotopic location of the stimulus, including pre-cortical areas, and the temporal components of stimulus driven activity that may persist over significant periods. Two computational modelling studies have been performed to explore these phenomena and are reported in this thesis. I) The plexus of long and short range lateral connections is a prominent feature of the layer 2/3 microcircuit in primary visual cortex. Despite the scope for possible functionality, the interdependence of local and long range circuits is still unclear. Spatiotemporal patterns of activity appear to be shaped by the underlying connectivity architecture and strong inhibition. A modelling study has been conducted to capture population activity that has been observed in vitro using voltage sensitive dyes. The model demonstrates that the precise spatiotemporal spread of activity seen in the cortical slice results from long range connections that target specific orientation domains whilst distinct regions of suppressed activity are shown to arise from local isotropic axonal projections. Distal excitatory activity resulting from long range axons is shaped by local interneurons similarly targeted by such connections. It is shown that response latencies of distal excitation are strongly influenced by frequency dependent facilitation and low threshold characteristics of interneurons. Together, these results support hypotheses made following experimental observations in vitro and clearly illustrate the underlying mechanisms. However, predictions by the model suggest that in vivo conditions give rise to markedly different spatiotemporal activity. Furthermore, opposing data in the literature regarding inter-laminar connectivity give rise to profoundly different spatiotemporal patterns of activity in cortex. 2) The second computational modelling study considers simple moving stimuli. These stimuli are implicated in the 'motion streak' phenomenon whereby the movement of a visual feature can give rise to trajectory information that is not explicitly present. Published experimental data of an in vivo study in the cat has shown that a single small light square moving stimulus elicits activity in populations of neurons in primary visual cortex that are selective for orientations parallel to stimulus trajectory (Jancke 2000). In more recent, unpublished data, this work is extended to consider long term persistent cortical activity that is generated by similar stimuli. These data indicate that following initial cortical activation that appears to result directly from the stimulus, iso-orientation domains display persistent activity. Furthermore, initial activity is broadly tuned with respect to orientation whilst later activity is strongly selective for orientations that are parallel to the stimulus trajectory. Currently the generative processes involved have not been clearly defined. Hence the proposed thesis will contribute to a more complete understanding of the mechanisms responsible for such cortical representations of moving visual stimuli. More specifically this will be achieved by a large scale mean field model that will enable a thorough investigation of the anatomical and electrophysiological elements concerned with the observed spatiotemporal dynamic behaviour and will represent a significant region of cortex. In conjunction, an existing computational model of the retina will be integrated. In doing so this thesis will offer the notion that certain cortical representations are inextricably linked with earlier stages of the visual pathway. As such consideration of retinal processing is fundamental to the understanding cortical functions and failure to do so can only result in erroneous conclusions

Sensory coding in supragranular cells of the vibrissal cortex in anesthetized and awake mice

Sensory perception entails reliable representation of the external stimuli as impulse activity of individual neurons (i.e. spikes) and neuronal populations in the sensory area. An ongoing challenge in neuroscience is to identify and characterize the features of the stimuli which are relevant to a specific sensory modality and neuronal strategies to effectively and efficiently encode those features. It is widely hypothesized that the neuronal populations employ “sparse coding” strategies to optimize the stimulus representations with a low energetic cost (i.e. low impulse activity). In the past two decades, a wealth of experimental evidence has supported this hypothesis by showing spatiotemporally sparse activity in sensory area. Despite numerous studies, the extent of sparse coding and its underlying mechanisms are not fully understood, especially in primary vibrissal somatosensory cortex (vS1), which is a key model system in sensory neuroscience. Importantly, it is not clear yet whether sparse activation of supragranular vS1 is due to insufficient synaptic input to the majority of the cells or the absence of effective stimulus features. In this thesis, first we asked how the choice of stimulus could affect the degree of sparseness and/or the overall fraction of the responsive vS1 neurons. We presented whisker deflections spanning a broad range of intensities, including “standard stimuli” and a high-velocity, “sharp” stimulus, which simulated the fast slip events that occur during whisker mediated object palpation. We used whole-cell and cell-attached recording and calcium imaging to characterize the neuronal responses to these stimuli. Consistent with previous literature, whole-cell recording revealed a sparse response to the standard range of velocities: although all recorded cells showed tuning to velocity in their postsynaptic potentials, only a small fraction produced stimulus-evoked spikes. In contrast, the sharp stimulus evoked reliable spiking in a large fraction of regular spiking neurons in the supragranular vS1. Spiking responses to the sharp stimulus were binary and precisely timed, with minimum trial-to-trial variability. Interestingly, we also observed that the sharp stimulus produced a consistent and significant reduction in action potential threshold. In the second step we asked whether the stimulus dependent sparse and dense activations we found in anesthetized condition would generalize to the awake condition. We employed cell-attached recordings in head-fixed awake mice to explore the degree of sparseness in awake cortex. Although, stimuli delivered by a piezo-electric actuator evoked significant response in a small fraction of regular spiking supragranular neurons (16%-29%), we observed that a majority of neurons (84%) were driven by manual probing of whiskers. Our results demonstrate that despite sparse activity, the majority of neurons in the superficial layers of vS1 contribute to coding by representing a specific feature of the tactile stimulus. Thesis outline: Chapter 1 provides a review of the current knowledge on sparse coding and an overview of the whisker-sensory pathway. Chapter 2 represents our published results regarding sparse and dense coding in vS1 of anesthetized mice (Ranjbar-Slamloo and Arabzadeh 2017). Chapter 3 represents our pending manuscript with results obtained with piezo and manual stimulation in awake mice. Finally, in Chapter 4 we discuss and conclude our findings in the context of the literature. The appendix provides unpublished results related to Chapter 2. This section is referenced in the final chapter for further discussion

A Thalamic Reticular Circuit for Head Direction Cell Tuning and Spatial Navigation.

As we navigate in space, external landmarks and internal information guide our movement. Circuit and synaptic mechanisms that integrate these cues with head-direction (HD) signals remain, however, unclear. We identify an excitatory synaptic projection from the presubiculum (PreS) and the multisensory-associative retrosplenial cortex (RSC) to the anterodorsal thalamic reticular nucleus (TRN), so far classically implied in gating sensory information flow. In vitro, projections to TRN involve AMPA/NMDA-type glutamate receptors that initiate TRN cell burst discharge and feedforward inhibition of anterior thalamic nuclei. In vivo, chemogenetic anterodorsal TRN inhibition modulates PreS/RSC-induced anterior thalamic firing dynamics, broadens the tuning of thalamic HD cells, and leads to preferential use of allo- over egocentric search strategies in the Morris water maze. TRN-dependent thalamic inhibition is thus an integral part of limbic navigational circuits wherein it coordinates external sensory and internal HD signals to regulate the choice of search strategies during spatial navigation

Characterization of response properties in the mouse lateral geniculate nucleus

The lateral geniculate nucleus (LGN) has been increasingly recognized to actively regulate information transmission to primary visual cortex (V1). Although efforts have been devoted to study its morphological and functional features, the full array of response characteristics in mouse LGN as well as their dependency on subjective state have been relatively unexplored. To address the question we recorded from mouse LGN with multisite-electrode-arrays (MEAs). From a dataset with 185 single units, our results revealed several exceptional response features in mouse LGN. We also demonstrated that subtypes, such as ON-/OFF-centre and transient/sustained cells exhibited functionally distinctive features, which might indicate parallel projections. To further compare response features from the full extent of mouse LGN, we developed a three-dimension (3D) LGN volume through histological approach. This volume explicitly captures morphological features of mouse LGN and provides the preciseness to classify location of single neuron into the anterior/middle/posterior LGN. Based on this categorization, we showed that response features were not regionally restricted within mouse LGN. We further examined neural activity with subjects in high or low isoflurane states. The distinct features in LFPs between the two states indicated that adjusting isoflurane concentration could provide a reliable and controllable experimental model to explore the state-dependent neural activity in mouse visual system. Subsequently, our results demonstrated that properties, including response latency, contrast sensitivity and spatial frequency properties were modulated by isoflurane concentration. Our current work suggests that mouse LGN can dynamically regulate information transmission to the cortex using numerous mechanisms, including responding mode, modulation of neuronal responses according to subjects’ states.Open Acces

Modeling the Emergence of Whisker Direction Maps in Rat Barrel Cortex

Based on measuring responses to rat whiskers as they are mechanically stimulated, one recent study suggests that barrel-related areas in layer 2/3 rat primary somatosensory cortex (S1) contain a pinwheel map of whisker motion directions. Because this map is reminiscent of topographic organization for visual direction in primary visual cortex (V1) of higher mammals, we asked whether the S1 pinwheels could be explained by an input-driven developmental process as is often suggested for V1. We developed a computational model to capture how whisker stimuli are conveyed to supragranular S1, and simulate lateral cortical interactions using an established self-organizing algorithm. Inputs to the model each represent the deflection of a subset of 25 whiskers as they are contacted by a moving stimulus object. The subset of deflected whiskers corresponds with the shape of the stimulus, and the deflection direction corresponds with the movement direction of the stimulus. If these two features of the inputs are correlated during the training of the model, a somatotopically aligned map of direction emerges for each whisker in S1. Predictions of the model that are immediately testable include (1) that somatotopic pinwheel maps of whisker direction exist in adult layer 2/3 barrel cortex for every large whisker on the rat's face, even peripheral whiskers; and (2) in the adult, neurons with similar directional tuning are interconnected by a network of horizontal connections, spanning distances of many whisker representations. We also propose specific experiments for testing the predictions of the model by manipulating patterns of whisker inputs experienced during early development. The results suggest that similar intracortical mechanisms guide the development of primate V1 and rat S1

Impact of the pulvinar on the ventral pathway of the cat visual cortex

Signals from the retina are relayed to the lateral geniculate nucleus from which they are sent to the primary visual cortex. At the cortical level, the information is transferred across several visual areas in which the complexity of the processing increases progressively. Anatomical and functional evidence demonstrate the existence of two main pathways in visual cortex processing distinct features of the visual information: the dorsal and ventral streams. Cortical areas composing the dorsal stream are implicated mostly in motion processing while those comprising the ventral stream are involved in the processing of form and colour. This classic view of the cortical functional organization is challenged by the existence of reciprocal connections of visual cortical areas with the thalamic nucleus named pulvinar. These connections allow the creation of a trans-thalamic pathway that parallels the cortico-cortical communications across the visual hierarchy. The main goal of the present thesis is twofold: first, to obtain a better comprehension of the processing of light increments and decrements in an area of the cat ventral stream (area 21a); second, to characterize the nature of the thalamo-cortical inputs from the cat lateral posterior nucleus (LP) to area 21a. In study #1, we investigated the spatiotemporal response profile of neurons from area 21a to light increments (brights) and decrements (darks) using a reverse correlation analysis of a sparse noise stimulus. Our findings showed that 21a neurons exhibited stronger responses to darks with receptive fields exhibiting larger dark subfields. However, no differences were found between the temporal dynamics of brights and darks. In comparison with the primary visual cortex, the dark preference in area 21a was found to be strongly enhanced, supporting the notion that the asymmetries between brights and darks are transmitted and amplified along the ventral stream. In study #2, we investigated the impact of the reversible pharmacological inactivation of the LP nucleus on the contrast response function (CRF) of neurons from area 21a and the primary visual cortex (area 17). The thalamic inactivation yielded distinct effects on both cortical areas. While in area 17 the LP inactivation caused a slight decrease in the response gain, in area 21a a strong increase was observed. Thus, our findings suggest that the LP exerts a modulatory influence on the cortical processing along the ventral stream with stronger impact on higher order extrastriate areas. Taken together, our findings allowed a better comprehension of the functional properties of the cat ventral stream and contributed to the current knowledge on the role of the pulvinar on the cortico-thalamo-cortical processing of visual information.Les signaux provenant de la rétine sont relayés dans le corps géniculé latéral où ils sont envoyés au cortex visuel primaire. L’information passe ensuite à travers plusieurs aires visuelles où la complexité du traitement augmente progressivement. Des données tant anatomiques que fonctionnelles ont démontré l’existence de deux voies principales qui traitent différentes propriétés de l’information visuelle : les voies dorsale et ventrale. Les aires corticales composant la voie dorsale sont impliquées principalement dans le traitement du mouvement tandis que les aires de la voie ventrale sont impliquées dans le traitement de la forme et de la couleur. Cette vision classique de l’organisation fonctionnelle du cortex est toutefois remise en question par l’existence de connections réciproques entre les aires corticales visuelles et le pulvinar, un noyau thalamique. En effet, ces connections permettent la création d’une voie trans-thalamique parallèle aux connections cortico-corticales à travers la hiérarchie visuelle. Le but principal de la présente thèse consiste en deux volets : le premier est d’obtenir une meilleure compréhension du traitement des incréments et décréments de la lumière dans une aire de la voie ventrale du chat (aire 21a); le second est de caractériser la nature des inputs thalamo-corticaux du noyau latéral postérieur (LP) à l’aire 21a chez le chat. Dans l’étude #1, nous avons investigué le profil spatiotemporel des réponses des neurones de l’aire 21a aux incréments (blancs) et décréments (noirs) de lumière en utilisant l’analyse de corrélation inverse d’un stimulus de bruit épars. Les neurones de l’aire 21a ont répondu plus fortement aux stimuli noirs, en montrant des champs récepteurs avec des sous-champs noirs plus larges. Cependant, aucune différence n’a été trouvée en ce qui concerne les dynamiques temporelles des réponses aux blancs et aux noirs. En comparaison avec le cortex visuel primaire, la préférence aux stimuli noirs dans l’aire 21a s’est avérée fortement augmentée. Ces données indiquent que les asymétries entre les réponses aux blancs et aux noirs sont transmises et amplifiées à travers la voie ventrale. Dans l’étude #2, nous avons investigué l’impact de l’inactivation pharmacologique réversible du noyau LP sur la fonction de réponse au contraste (CRF) des neurones de l’aire 21a et du cortex visuel primaire (aire 17). L’inactivation a eu différents effets dans les deux aires corticales. Alors que, dans l’aire 17, l’inactivation du LP a causé une légère réduction du gain de la réponse, une forte augmentation a été observée dans l’aire 21a. Ainsi, nos résultats suggèrent que le LP exerce une influence modulatrice dans le traitement cortical à travers la voie ventrale avec un impact plus important dans des aires extrastriées de plus haut niveau. Nos résultats ont permis d’avoir une meilleure compréhension des propriétés fonctionnelles de la voie ventrale du chat et de contribuer à enrichir les connaissances actuelles sur le rôle du pulvinar dans le traitement cortico-thalamo-cortical de l’information visuelle

Synchrony between orientation-selective neurons is modulated during adaptation-induced plasticity in cat visual cortex

<p>Abstract</p> <p>Background</p> <p>Visual neurons respond essentially to luminance variations occurring within their receptive fields. In primary visual cortex, each neuron is a filter for stimulus features such as orientation, motion direction and velocity, with the appropriate combination of features eliciting maximal firing rate. Temporal correlation of spike trains was proposed as a potential code for linking the neuronal responses evoked by various features of a same object. In the present study, synchrony strength was measured between cells following an adaptation protocol (prolonged exposure to a non-preferred stimulus) which induce plasticity of neurons' orientation preference.</p> <p>Results</p> <p>Multi-unit activity from area 17 of anesthetized adult cats was recorded. Single cells were sorted out and (1) orientation tuning curves were measured before and following 12 min adaptation and 60 min after adaptation (2) pairwise synchrony was measured by an index that was normalized in relation to the cells' firing rate. We first observed that the prolonged presentation of a non-preferred stimulus produces attractive (58%) and repulsive (42%) shifts of cell's tuning curves. It follows that the adaptation-induced plasticity leads to changes in preferred orientation difference, i.e. increase or decrease in tuning properties between neurons. We report here that, after adaptation, the neuron pairs that shared closer tuning properties display a significant increase of synchronization. Recovery from adaptation was accompanied by a return to the initial synchrony level.</p> <p>Conclusion</p> <p>We conclude that synchrony reflects the similarity in neurons' response properties, and varies accordingly when these properties change.</p

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)