Audio-visual detection benefits in the rat

Human psychophysical studies have described multisensory perceptual benefits such as enhanced detection rates and faster reaction times in great detail. However, the neural circuits and mechanism underlying multisensory integration remain difficult to study in the primate brain. While rodents offer the advantage of a range of experimental methodologies to study the neural basis of multisensory processing, rodent studies are still limited due to the small number of available multisensory protocols. We here demonstrate the feasibility of an audio-visual stimulus detection task for rats, in which the animals detect lateralized uni- and multi-sensory stimuli in a two-response forced choice paradigm. We show that animals reliably learn and perform this task. Reaction times were significantly faster and behavioral performance levels higher in multisensory compared to unisensory conditions. This benefit was strongest for dim visual targets, in agreement with classical patterns of multisensory integration, and was specific to task-informative sounds, while uninformative sounds speeded reaction times with little costs for detection performance. Importantly, multisensory benefits for stimulus detection and reaction times appeared at different levels of task proficiency and training experience, suggesting distinct mechanisms inducing these two multisensory benefits. Our results demonstrate behavioral multisensory enhancement in rats in analogy to behavioral patterns known from other species, such as humans. In addition, our paradigm enriches the set of behavioral tasks on which future studies can rely, for example to combine behavioral measurements with imaging or pharmacological studies in the behaving animal or to study changes of integration properties in disease models

Asymmetric multisensory interactions of visual and somatosensory responses in a region of the rat parietal cortex

Perception greatly benefits from integrating multiple sensory cues into a unified percept. To study the neural mechanisms of sensory integration, model systems are required that allow the simultaneous assessment of activity and the use of techniques to affect individual neural processes in behaving animals. While rodents qualify for these requirements, little is known about multisensory integration and areas involved for this purpose in the rodent. Using optical imaging combined with laminar electrophysiological recordings, the rat parietal cortex was identified as an area where visual and somatosensory inputs converge and interact. Our results reveal similar response patterns to visual and somatosensory stimuli at the level of current source density (CSD) responses and multi-unit responses within a strip in parietal cortex. Surprisingly, a selective asymmetry was observed in multisensory interactions: when the somatosensory response preceded the visual response, supra-linear summation of CSD was observed, but the reverse stimulus order resulted in sub-linear effects in the CSD. This asymmetry was not present in multi-unit activity however, which showed consistently sub-linear interactions. These interactions were restricted to a specific temporal window, and pharmacological tests revealed significant local intra-cortical contributions to this phenomenon. Our results highlight the rodent parietal cortex as a system to model the neural underpinnings of multisensory processing in behaving animals and at the cellular level

Integrative function in rat visual system

A vital function of the brain is to acquire information about the events in the environment and to respond appropriately. The brain needs to integrate the incoming information from multiple senses to improve the quality of the sensory signal. It also needs to be able to distribute the processing resources to optimise the integration across modalities based on the reliability and salience of the incoming signals. This thesis aimed to investigate two aspects of the way in which the brain integrates information from the external environment: multisensory integration and selective attention. The hooded rat was used as the experimental animal model. In Chapter 2 of this thesis, I investigate the multisensory properties of neurons in superior colliculus (SC), a midbrain structure involved in attentive and orienting behaviours. I first establish that in rat SC, spiking activity is elevated by whisker or visual stimuli, but rarely both, when those stimuli are presented in isolation. I then show that visually responsive sites are mainly found in superficial layers whereas whisker responsive sites were in intermediate layers. Finally I show that there are robust suppressive interactions between these two modalities. In Chapter 3, I develop a rodent behavioural paradigm that can easily be paired with electrophysiological measurements. The design is adaptable to a variety of detection and discrimination tasks. Head position is restricted in the central nose-poke without head-fixation and the eyes can be constantly monitored via video camera. In Chapter 4, I ask whether selective spatial visual attention can be demonstrated in rats utilising the paradigms developed in Chapter 3. Selective attention is the process by which brain focuses on significant external events. Does being able to predict the likely side of the stimulus modulate the speed and accuracy of stimulus detection? To address this question, I varied the probability with which the signal was presented on left or right screen. My results suggest that rats have the capacity for spatial attention engaged by top-down mechanisms that have access to the predictability of stimulus location. In summary, my thesis presents a paradigm to study visual behaviour, multisensory integration and selective spatial attention in rats. Over the last decade, rats have gained popularity as a viable animal model in sensory systems neuroscience because of the access to the array of genetic tools and in vivo electrophysiology and imaging techniques. As such the paradigms developed here provide a useful preparation to complement the existing well-established primate models

Functional role of the Oc2M cortical area in the processing of multimodal sensory inputs in rats

Tese de mestrado, Neurociências, Universidade de Lisboa, Faculdade de Medicina, 2020Quase todos os organismos dotados de um sistema nervoso são confrontados, diariamente, com uma grande variedade de estímulos sensoriais. A forma como os animais (humanos e não-humanos) interagem com o mundo externo, está dependente da capacidade de integração das várias informações sensoriais em seu redor. Esta integração permite formar uma percepção coesa do ambiente envolta, como também possibilita a extração de informação relevante para tomar decisões comportamentais adequadas. Por outro lado, os sistemas sensoriais não processam informação isoladamente, e o conteúdo multissensorial presente nas nossas memórias episódicas sugere que, de alguma forma, o processamento de estímulos sensoriais está intrinsecamente relacionado com a formação e armazenamento de memórias. O registo electrofisiológico in vivo da atividade neuronal em cérebros de modelos animais oferece a possibilidade de correlacionar a atividade cerebral detectada em específicas regiões do cérebro, com determinados outputs comportamentais. Este tipo experiências levaram à descoberta de células presentes no hipocampo, chamadas de ‘place cells’ (O’Keefe & Dostrovsky, 1971), que se acredita serem responsáveis pela formação de um mapa cognitivo que orienta a navegação no espaço (Keefe, 1976). Estas células podem representar não só a localização atual do animal, assim como localizações anteriores e futuras (Ferbinteanu & Shapiro, 2003; Frank, Brown, & Wilson, 2000). Mais tarde, a descoberta de neurónios com outras propriedades espaciais, tais como as ‘células- grelha’ (grid-cells, Hafting et al., 2005) células ‘head-direction’ (Sargolini et al., 2006) ou as células ‘border’ (Solstad, 2008), contribuíram para um maior entendimento acerca de como o cérebro codifica e organiza informação sensorial à sua volta, na forma de um mapa cognitivo espacial. Contudo, as regiões e os mecanismos subjacentes que levam à formação destes mapas cognitivos, com base na integração de estímulos sensoriais primários, ainda não são conhecidos. Este projeto explora a região anatómica no cérebro do rato, designada como Oc2M, como um possível local de convergência na integração de informação multimodal, crucial para a formação de memórias num contexto sensorial. Estudos anteriores mostraram que a região Oc2M, tradicionalmente considerada como uma região visual secundária, está de facto envolvida no processamento de estímulos visuais e auditivos, assim como na sua localização espacial. Para além disso, estudos recentes do nosso laboratório, revelaram que neurónios em Oc2M recebem projeções de todos os córtices sensoriais primários, alguns córtices sensoriais secundários, alguns núcleos do tálamo, e do hipocampo. Com base na utilização de ferramentas de optogenética para a estimulação in vitro dos inputs sinápticos em Oc2M, verificou-se que os córtices primários visual e auditivo estabelecem sinapses funcionais com a região Oc2M (Quintino & Remondes, 2017 não-publicado). Evidências preliminares do nosso laboratório de registos extracelulares in vivo da região Oc2M, mostraram que esta região responde a estímulos de som e luz, com uma distinta organização temporal (Cardoso & Remondes, 2017, não-publicado). Neste projeto começámos por desenvolver uma tarefa comportamental com o objectivo de captar – in vivo - a dependência funcional entre Oc2M e Hipocampo. Nestas tarefa os animais são colocados num labirinto, e são treinados para associar um determinado estímulo (componente sensorial) com uma específica trajetória (componente de memória). Os resultados comportamentais mostraram que dois, dos seis animais treinados, conseguiram aprender a tarefa. Estes mostraram uma progressão de aprendizagem linear ao longo do tempo, e conseguiram manter de forma consistente uma taxa de acerto acima de ‘chance level’ (probabilidade de acerto atribuída ao acaso) para cada uma das modalidades sensoriais. Estes animais foram depois sujeitos a um período de interrupção de 33 dias, para serem novamente treinados na tarefa, desta vez com a duração da pista sensorial reduzida para metade (500 milissegundos em vez de 1 segundo). Os ratos conseguiram não só reaprender a tarefa com um nível de dificuldade mais acentuado, assim como ambos precisaram de menos sessões para atingir as performances esperadas. Os registos eletrofisiológicos foram obtidos através de um dispositivo chamado ‘hyperdrive’. A ‘hyperdrive’ é uma estrutura com 30 tétrodos movíveis, construída no laboratório, e implantada no cérebro do rato através de uma cirurgia estereotáxica, com os vários tétrodos colocados nas regiões de interesse (neste caso, Oc2M e Hipocampo). Cada tétrodo é composto por quatro canais que registam de forma independente a atividade neuronal da região cerebral onde se encontram inseridos. Desta forma, para além de registarmos os valores correspondentes à voltagem extracelular de determinado local (sinal chamado de ‘local field potential’, LFP), conseguimos também identificar e isolar a atividade proveniente de diversos neurónios representativos do local de interesse, e correlacionar essa atividade com variáveis comportamentais. No presente trabalho apresentamos dados de eletrofisiologia in vivo de 2 ratos implantados, com registo da atividade em Oc2M e Hipocampo, em resposta a estímulos sensoriais num protocolo passivo de estimulação chamado de ‘Stimbox’. Neste paradigma experimental, os animais são colocados numa caixa (50 x 30 x 60 cm) onde são sujeitos a 3 condições diferentes de estimulação sensorial: som, luz, e som + luz em simultâneo. Análises realizadas ao LFP revelaram que, após a apresentação do estímulo, apenas as condições de luz e som + luz provocaram uma resposta evidente em ambas as áreas, Oc2M e Hipocampo. O facto de estas duas condições não terem apresentado respostas estatisticamente significativas entre si, sugere que apenas a estimulação visual foi responsável pelos transientes observados na atividade do LFP. Contudo, a identificação de subpopulações de neurónios em Oc2M, e a posterior análise aos potenciais de ação gerados com base na sua frequência de disparos, revelou a existência de células em Oc2M que respondem de forma distinta aos mesmos estímulos sensoriais. Ademais, as respostas observadas por neurónios em Oc2M em resposta à luz e à luz + som em simultâneo, mostraram-se significativamente diferentes, sugerindo assim um efeito modulatório do som na atividade de Oc2M, quando apresentado em combinação com um estímulo visual. Estes resultados suportam a hipótese de Oc2M como uma área de associação multissensorial, possível homólogo do córtex parietal posterior nos seres humanos. Embora não tenha sido possível realizar, planeamos como futuras experiências o registo simultâneo da atividade neuronal em Oc2M e Hipocampo com ratos a desempenhar a SCTAT. Tal irá ajudar-nos a perceber as computações subjacentes à integração de inputs sensoriais por parte do Oc2M, e como é que essa informação é transferida e utilizada pelo hipocampo numa tarefa de tomada- de-decisão perceptual. Outro objectivo futuro será a supressão seletiva da atividade celular em Oc2M durante sessões da SCTAT, recorrendo a técnicas da engenharia genética tais como chemogenetics (Armbruster et al., 2007) ou optogenética (Boyden et al., 2005). Estas experiências permitir-nos-ia testar, de forma causal, a hipótese de Oc2M como um local de convergência no processamento de informação sensorial relevante.The hippocampal system has long been associated with episodic memory. The discovery of place cells (O’Keefe & Dostrovsky, 1971) and entorhinal grid cells (Hafting et al., 2005) led to a major insight on how the brain encodes and organizes sensory information in the form of a spatial contextual map. However, little is known concerning the mechanisms underlying the integration of primary sensory stimuli in such a way as to convert it into the hippocampal spatial maps. Previous studies and preliminary data from our lab suggest that the cortical region of the rat’s brain Oc2M might play a critical role in the integration of multimodal sensory information in the service of spatial navigation. We established a behavioral task aimed to test the functional inter- dependency between Oc2M and Hippocampus. In the sensory-cue trajectory association task (SCTAT), rats are required to associate a particular sensory stimulus, sound or light, with a specific trajectory on a modified T-maze. Our results showed that 2 out of 6 animals were able to learn the SCTAT, having reached performance levels of above 80% for both sensory modalities. Additionally, after an interruption period of 33 days, we observed that these two rats were not only able to relearn the task with a shortened stimulus duration (500 milliseconds), but they also needed fewer sessions to achieve performances above chance level. An ‘hyperdrive’ array of 30 independently movable tetrodes was built and chronically implanted in the rat’s brain, targeted to Oc2M and Hippocampus. Each tetrode comprises four independent channels that record intra-cerebrally the extracellular electrical potential, which allow us to identify single neurons’ activity and correlate it with behavior. In the current work, we present in-vivo electrophysiological data from two implanted rats, regarding Oc2M and Hippocampus activity, in response to sensory cues in a passive-stimulation protocol called ‘Stimbox’. This protocol is composed by 3 sensory conditions: light stimulation, sound stimulation, and light and sound combined stimulation. Analyses of the local field potential (LFP) activity showed that, after stimulus onset, only light and sound + light conditions elicited a clear response in both Oc2M and Hippocampus. The fact the light and sound + light conditions were not significantly different, suggests that only light itself was responsible for the observed changes in LFP activity. However, we found neuronal ensembles in Oc2M that exhibited significantly different responses, in terms of firing rate, to the same sensory cues. Importantly, Oc2M neurons’ responses to light and sound + light cues were found to be different, thus suggesting a modulatory effect of the sound stimulus once paired with a light cue. Such supports the hypothesis of Oc2M as a multimodal association area, comparable to the human posterior parietal cortex. As future experiments, neuronal recordings of Oc2M and Hippocampus while rats perform the SCTAT would shed light on how Oc2M integrates sensory inputs, and how it conveys information to hippocampus in a perceptual decision- making task. Furthermore, the use of genetic tools to selectively suppress Oc2M’s cellular activity during the SCTAT, such as chemogenetic (Ambruster et al., 2007) or optogenetic (Boyden et al., 2005), would further lead to causally test our long-term hypothesis of Oc2M as a site of convergence to process sensory- relevant information

Perceptual Strategies and Neuronal Underpinnings underlying Pattern Recognition through Visual and Tactile Sensory Modalities in Rats

The aim of my PhD project was to investigate multisensory perception and multimodal recognition abilities in the rat, to better understand the underlying perceptual strategies and neuronal mechanisms. I have chosen to carry out this project on the laboratory rat, for two reasons. First, the rat is a flexible and highly accessible experimental model, where it is possible to combine state-of-the-art neurophysiological approaches (such as multi-electrode neuronal recordings) with behavioral investigation of perception and (more in general) cognition. Second, extensive research concerning multimodal integration has already been conducted in this species, both at the neurophysiological and behavioral level. My thesis work has been organized in two projects: a psychophysical assessment of object categorization abilities in rats, and a neurophysiological study of neuronal tuning in the primary visual cortex of anaesthetized rats. In both experiments, unisensory (visual and tactile) and multisensory (visuo-tactile) stimulation has been used for training and testing, depending on the task. The first project has required development of a new experimental rig for the study of object categorization in rat, using solid objects, so as to be able to assess their recognition abilities under different modalities: vision, touch and both together. The second project involved an electrophysiological study of rat primary visual cortex, during visual, tactile and visuo-tactile stimulation, with the aim of understanding whether any interaction between these modalities exists, in an area that is mainly deputed to one of them. The results of both of the studies are still preliminary, but they already offer some interesting insights on the defining features of these abilities

Multisensory and Motor Representations in Rat Oral Somatosensory Cortex

Abstract In mammals, a complex array of oral sensors assess the taste, temperature and haptic properties of food. Although the representation of taste has been extensively studied in the gustatory cortex, it is unclear how the somatosensory cortex encodes information about the properties of oral stimuli. Moreover, it is poorly understood how different oral sensory modalities are integrated and how sensory responses are translated into oral motor actions. To investigate whether oral somatosensory cortex processes food-related sensations and movements, we performed in vivo whole-cell recordings and motor mapping experiments in rats. Neurons in oral somatosensory cortex showed robust post-synaptic and sparse action potential responses to air puffs. Membrane potential showed that cold water evoked larger responses than room temperature or hot water. Most neurons showed no clear tuning of responses to bitter, sweet and neutral gustatory stimuli. Finally, motor mapping experiments with histological verification revealed an initiation of movements related to food consumption behavior, such as jaw opening and tongue protrusions. We conclude that somatosensory cortex: (i) provides a representation of the temperature of oral stimuli, (ii) does not systematically encode taste information and (iii) influences orofacial movements related to food consummatory behavior

The Behavioral Relevance of Multisensory Neural Response Interactions

Sensory information can interact to impact perception and behavior. Foods are appreciated according to their appearance, smell, taste and texture. Athletes and dancers combine visual, auditory, and somatosensory information to coordinate their movements. Under laboratory settings, detection and discrimination are likewise facilitated by multisensory signals. Research over the past several decades has shown that the requisite anatomy exists to support interactions between sensory systems in regions canonically designated as exclusively unisensory in their function and, more recently, that neural response interactions occur within these same regions, including even primary cortices and thalamic nuclei, at early post-stimulus latencies. Here, we review evidence concerning direct links between early, low-level neural response interactions and behavioral measures of multisensory integration

Virtual Reality system for freely-moving rodents

Spatial navigation, active sensing, and most cognitive functions rely on a tight link between motor output and sensory input. Virtual reality (VR) systems simulate the sensorimotor loop, allowing flexible manipulation of enriched sensory input. Conventional rodent VR systems provide 3D visual cues linked to restrained locomotion on a treadmill, leading to a mismatch between visual and most other sensory inputs, sensory-motor conflicts, as well as restricted naturalistic behavior. To rectify these limitations, we developed a VR system (ratCAVE) that provides realistic and low-latency visual feedback directly to head movements of completely unrestrained rodents. Immersed in this VR system, rats displayed naturalistic behavior by spontaneously interacting with and hugging virtual walls, exploring virtual objects, and avoiding virtual cliffs. We further illustrate the effect of ratCAVE-VR manipulation on hippocampal place fields. The newly-developed methodology enables a wide range of experiments involving flexible manipulation of visual feedback in freely-moving behaving animals

Visuo-auditory interactions in the primary visual cortex of the behaving monkey: Electrophysiological evidence

<p>Abstract</p> <p>Background</p> <p>Visual, tactile and auditory information is processed from the periphery to the cortical level through separate channels that target primary sensory cortices, from which it is further distributed to functionally specialized areas. Multisensory integration is classically assigned to higher hierarchical cortical areas, but there is growing electrophysiological evidence in man and monkey of multimodal interactions in areas thought to be unimodal, interactions that can occur at very short latencies. Such fast timing of multisensory interactions rules out the possibility of an origin in the polymodal areas mediated through back projections, but is rather in favor of heteromodal connections such as the direct projections observed in the monkey, from auditory areas (including the primary auditory cortex AI) directly to the primary visual cortex V1. Based on the existence of such AI to V1 projections, we looked for modulation of neuronal visual responses in V1 by an auditory stimulus in the awake behaving monkey.</p> <p>Results</p> <p>Behavioral or electrophysiological data were obtained from two behaving monkeys. One monkey was trained to maintain a passive central fixation while a peripheral visual (V) or visuo-auditory (AV) stimulus was presented. From a population of 45 V1 neurons, there was no difference in the mean latencies or strength of visual responses when comparing V and AV conditions. In a second active task, the monkey was required to orient his gaze toward the visual or visuo-auditory stimulus. From a population of 49 cells recorded during this saccadic task, we observed a significant reduction in response latencies in the visuo-auditory condition compared to the visual condition (mean 61.0 vs. 64.5 ms) only when the visual stimulus was at midlevel contrast. No effect was observed at high contrast.</p> <p>Conclusion</p> <p>Our data show that single neurons from a primary sensory cortex such as V1 can integrate sensory information of a different modality, a result that argues against a strict hierarchical model of multisensory integration. Multisensory interaction in V1 is, in our experiment, expressed by a significant reduction in visual response latencies specifically in suboptimal conditions and depending on the task demand. This suggests that neuronal mechanisms of multisensory integration are specific and adapted to the perceptual features of behavior.</p

A multimodal pathway including the basal ganglia in the feline brain

The purpose of this paper is to give an overview of our present knowledge about the feline tecto-thalamo-basal ganglia cortical sensory pathway. We reviewed morphological and electrophysiological studies of the cortical areas, located in ventral bank of the anterior ectosylvian sulcus as well as the region of the insular cortex, the suprageniculate nucleus of the thalamus, caudate nucleus, and the substantia nigra. Microelectrode studies revealed common receptive field properties in all these structures. The receptive fields were extremely large and multisensory, with pronounced sensitivity to motion of visual stimuli. They often demonstrated directional and velocity selectivity. Preference for small visual stimuli was also a frequent finding. However, orientation sensitivity was absent. It became obvious that the structures of the investigated sensory loop exhibit a unique kind of information processing, not found anywhere else in the feline visual system