RESUMEN
Coordinated activity across networks of neurons is a hallmark of both resting and active behavioural states in many species1-5. These global patterns alter energy metabolism over seconds to hours, which underpins the widespread use of oxygen consumption and glucose uptake as proxies of neural activity6,7. However, whether changes in neural activity are causally related to metabolic flux in intact circuits on the timescales associated with behaviour is unclear. Here we combine two-photon microscopy of the fly brain with sensors that enable the simultaneous measurement of neural activity and metabolic flux, across both resting and active behavioural states. We demonstrate that neural activity drives changes in metabolic flux, creating a tight coupling between these signals that can be measured across brain networks. Using local optogenetic perturbation, we demonstrate that even transient increases in neural activity result in rapid and persistent increases in cytosolic ATP, which suggests that neuronal metabolism predictively allocates resources to anticipate the energy demands of future activity. Finally, our studies reveal that the initiation of even minimal behavioural movements causes large-scale changes in the pattern of neural activity and energy metabolism, which reveals a widespread engagement of the brain. As the relationship between neural activity and energy metabolism is probably evolutionarily ancient and highly conserved, our studies provide a critical foundation for using metabolic proxies to capture changes in neural activity.
Asunto(s)
Conducta Animal , Encéfalo/citología , Encéfalo/fisiología , Drosophila melanogaster/metabolismo , Drosophila melanogaster/fisiología , Redes y Vías Metabólicas , Neuronas/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Encéfalo/metabolismo , Drosophila melanogaster/citología , Metabolismo Energético , Femenino , Masculino , Vías Nerviosas , Optogenética , DescansoRESUMEN
A major goal in neuroscience is to understand how populations of neurons code for stimuli or actions. While the number of neurons that can be recorded simultaneously is increasing at a fast pace, in most cases these recordings cannot access a complete population: some neurons that carry relevant information remain unrecorded. In particular, it is hard to simultaneously record all the neurons of the same type in a given area. Recent progress have made possible to profile each recorded neuron in a given area thanks to genetic and physiological tools, and to pool together recordings from neurons of the same type across different experimental sessions. However, it is unclear how to infer the activity of a full population of neurons of the same type from these sequential recordings. Neural networks exhibit collective behaviour, e.g. noise correlations and synchronous activity, that are not directly captured by a conditionally-independent model that would just put together the spike trains from sequential recordings. Here we show that we can infer the activity of a full population of retina ganglion cells from sequential recordings, using a novel method based on copula distributions and maximum entropy modeling. From just the spiking response of each ganglion cell to a repeated stimulus, and a few pairwise recordings, we could predict the noise correlations using copulas, and then the full activity of a large population of ganglion cells of the same type using maximum entropy modeling. Remarkably, we could generalize to predict the population responses to different stimuli with similar light conditions and even to different experiments. We could therefore use our method to construct a very large population merging cells' responses from different experiments. We predicted that synchronous activity in ganglion cell populations saturates only for patches larger than 1.5mm in radius, beyond what is today experimentally accessible.
Asunto(s)
Potenciales de Acción/fisiología , Modelos Neurológicos , Red Nerviosa , Neuronas/fisiología , Animales , Biología Computacional , Red Nerviosa/citología , Red Nerviosa/fisiología , Ratas , Células Ganglionares de la Retina/fisiologíaRESUMEN
In many cases of inherited retinal degenerations, ganglion cells are spared despite photoreceptor cell death, making it possible to stimulate them to restore visual function. Several studies have shown that it is possible to express an optogenetic protein in ganglion cells and make them light sensitive, a promising strategy to restore vision. However the spatial resolution of optogenetically-reactivated retinas has rarely been measured, especially in the primate. Since the optogenetic protein is also expressed in axons, it is unclear if these neurons will only be sensitive to the stimulation of a small region covering their somas and dendrites, or if they will also respond to any stimulation overlapping with their axon, dramatically impairing spatial resolution. Here we recorded responses of mouse and macaque retinas to random checkerboard patterns following an in vivo optogenetic therapy. We show that optogenetically activated ganglion cells are each sensitive to a small region of visual space. A simple model based on this small receptive field predicted accurately their responses to complex stimuli. From this model, we simulated how the entire population of light sensitive ganglion cells would respond to letters of different sizes. We then estimated the maximal acuity expected by a patient, assuming it could make an optimal use of the information delivered by this reactivated retina. The obtained acuity is above the limit of legal blindness. Our model also makes interesting predictions on how acuity might vary upon changing the therapeutic strategy, assuming an optimal use of the information present in the retinal activity. Optogenetic therapy could thus potentially lead to high resolution vision, under conditions that our model helps to determinine.
Asunto(s)
Ceguera , Optogenética/métodos , Células Ganglionares de la Retina/fisiología , Animales , Ceguera/fisiopatología , Ceguera/terapia , Terapia Genética , Macaca , Ratones , Modelos Biológicos , Retina/fisiología , Agudeza Visual/fisiologíaRESUMEN
Neural noise sets a limit to information transmission in sensory systems. In several areas, the spiking response (to a repeated stimulus) has shown a higher degree of regularity than predicted by a Poisson process. However, a simple model to explain this low variability is still lacking. Here we introduce a new model, with a correction to Poisson statistics, that can accurately predict the regularity of neural spike trains in response to a repeated stimulus. The model has only two parameters but can reproduce the observed variability in retinal recordings in various conditions. We show analytically why this approximation can work. In a model of the spike-emitting process where a refractory period is assumed, we derive that our simple correction can well approximate the spike train statistics over a broad range of firing rates. Our model can be easily plugged to stimulus processing models, like a linear-nonlinear model or its generalizations, to replace the Poisson spike train hypothesis that is commonly assumed. It estimates the amount of information transmitted much more accurately than Poisson models in retinal recordings. Thanks to its simplicity, this model has the potential to explain low variability in other areas.
Asunto(s)
Modelos Neurológicos , Células Ganglionares de la Retina/fisiología , Animales , Dinámicas no Lineales , RatasRESUMEN
Retina is a paradigmatic system for studying sensory encoding: the transformation of light into spiking activity of ganglion cells. The inverse problem, where stimulus is reconstructed from spikes, has received less attention, especially for complex stimuli that should be reconstructed "pixel-by-pixel". We recorded around a hundred neurons from a dense patch in a rat retina and decoded movies of multiple small randomly-moving discs. We constructed nonlinear (kernelized and neural network) decoders that improved significantly over linear results. An important contribution to this was the ability of nonlinear decoders to reliably separate between neural responses driven by locally fluctuating light signals, and responses at locally constant light driven by spontaneous-like activity. This improvement crucially depended on the precise, non-Poisson temporal structure of individual spike trains, which originated in the spike-history dependence of neural responses. We propose a general principle by which downstream circuitry could discriminate between spontaneous and stimulus-driven activity based solely on higher-order statistical structure in the incoming spike trains.
Asunto(s)
Potenciales de Acción/fisiología , Biología Computacional/métodos , Modelos Neurológicos , Retina/fisiología , Animales , Masculino , Redes Neurales de la Computación , Dinámicas no Lineales , Ratas , Ratas Long-EvansRESUMEN
In recent years, multielectrode arrays and large silicon probes have been developed to record simultaneously between hundreds and thousands of electrodes packed with a high density. However, they require novel methods to extract the spiking activity of large ensembles of neurons. Here, we developed a new toolbox to sort spikes from these large-scale extracellular data. To validate our method, we performed simultaneous extracellular and loose patch recordings in rodents to obtain 'ground truth' data, where the solution to this sorting problem is known for one cell. The performance of our algorithm was always close to the best expected performance, over a broad range of signal-to-noise ratios, in vitro and in vivo. The algorithm is entirely parallelized and has been successfully tested on recordings with up to 4225 electrodes. Our toolbox thus offers a generic solution to sort accurately spikes for up to thousands of electrodes.
Asunto(s)
Potenciales de Acción/fisiología , Electrodos , Electrofisiología/instrumentación , Neuronas Retinianas/fisiología , Algoritmos , Animales , Simulación por Computador , Electrofisiología/métodos , Masculino , Ratones , Modelos Neurológicos , Ratas Long-Evans , Procesamiento de Señales Asistido por ComputadorRESUMEN
In the early visual system, cells of the same type perform the same computation in different places of the visual field. How these cells code together a complex visual scene is unclear. A common assumption is that cells of a single-type extract a single-stimulus feature to form a feature map, but this has rarely been observed directly. Using large-scale recordings in the rat retina, we show that a homogeneous population of fast OFF ganglion cells simultaneously encodes two radically different features of a visual scene. Cells close to a moving object code quasilinearly for its position, while distant cells remain largely invariant to the object's position and, instead, respond nonlinearly to changes in the object's speed. We develop a quantitative model that accounts for this effect and identify a disinhibitory circuit that mediates it. Ganglion cells of a single type thus do not code for one, but two features simultaneously. This richer, flexible neural map might also be present in other sensory systems.
Asunto(s)
Simulación por Computador , Retina/citología , Retina/fisiología , Células Ganglionares de la Retina/citología , Células Ganglionares de la Retina/fisiología , Células Amacrinas/fisiología , Animales , Femenino , Masculino , Modelos Teóricos , Percepción de Movimiento/fisiología , Estimulación Luminosa/métodos , Ratas , Campos VisualesRESUMEN
Recent experimental results based on multielectrode and imaging techniques have reinvigorated the idea that large neural networks operate near a critical point, between order and disorder. However, evidence for criticality has relied on the definition of arbitrary order parameters, or on models that do not address the dynamical nature of network activity. Here we introduce a novel approach to assess criticality that overcomes these limitations, while encompassing and generalizing previous criteria. We find a simple model to describe the global activity of large populations of ganglion cells in the rat retina, and show that their statistics are poised near a critical point. Taking into account the temporal dynamics of the activity greatly enhances the evidence for criticality, revealing it where previous methods would not. The approach is general and could be used in other biological networks.