A5081202932- Neural dynamics and brain function
- Photoreceptor and optogenetics research
- Neuroscience and Neuropharmacology Research
- EEG and Brain-Computer Interfaces
- Neuroscience and Neural Engineering
- Advanced Memory and Neural Computing
- Visual perception and processing mechanisms
- Retinal Diseases and Treatments
- Retinal Imaging and Analysis
- Functional Brain Connectivity Studies
- stochastic dynamics and bifurcation
- Neural and Behavioral Psychology Studies
- Memory and Neural Mechanisms
- Olfactory and Sensory Function Studies
- Retinal Development and Disorders
- Advanced Fluorescence Microscopy Techniques
- Glaucoma and retinal disorders
- Cognitive Science and Mapping
- Neurobiology and Insect Physiology Research
- Neural Networks and Applications
- Receptor Mechanisms and Signaling
- Eicosanoids and Hypertension Pharmacology
- Gaze Tracking and Assistive Technology
- Renal and Vascular Pathologies
- Retinal and Optic Conditions
National Institutes of Health
2017-2024
National Institute of Mental Health
2017-2024
Harvard University
2009-2013
Gloucestershire Hospitals NHS Foundation Trust
2013
Cheltenham General Hospital
2013
Howard Hughes Medical Institute
2011
Massachusetts Institute of Technology
2006-2011
Boston University
2011
KU Leuven
2011
Neuroelectronics Research Flanders
2011
Many thousands of cortical neurons are activated by any single sensory stimulus, but the organization these populations is poorly understood. For example, in mouse visual cortex—whose preferred orientations arranged randomly—organized with respect to other response properties? Using high-speed vivo two-photon calcium imaging, we characterized receptive fields up 100 excitatory and inhibitory a 200 μm imaged plane. Inhibitory had nonlinearly summating, complex-like were weakly tuned for...
In mammals, the lateral geniculate nucleus (LGN) and superior colliculus (SC) are major targets of visual inputs from retina. The LGN projects mainly to primary cortex (V1) while SC thalamus brainstem, providing two potential pathways for processing inputs. Indeed, cortical lesion experiments in rodents have yielded mixed results, leading hypothesis that performance simple behaviors may involve computations performed entirely by this subcortical pathway through SC. However, these previous...
Many cortical network models use recurrent coupling strong enough to require inhibition for stabilization. Yet it has been experimentally unclear whether inhibition-stabilized (ISN) describe function well across areas and states. Here, we test several ISN predictions, including the counterintuitive (paradoxical) suppression of inhibitory firing in response optogenetic stimulation. We find clear evidence operation mouse visual, somatosensory, motor cortex. Simple two-population data let us...
To understand how activity in mammalian neural circuits controls behavior, the mouse is a promising model system due to convergence of genetic, optical, and physiological methods. The ability control quantify behavior precisely also essential for these studies. We developed an operant visual detection paradigm make psychophysical measurements: head-fixed mice responses by pressing lever. designed this task permit neurophysiological studies cerebral cortex, where variable from trial neurons...
Significance The brain performs computations by transforming sensory inputs to make decisions. We study these neuronal in the mouse, one of smallest animals with a cerebral cortex, part human that controls complex behavior. find animals’ behavior can be insensitive timing cortical inputs, depending only on total spike count, even though individual neurons are sensitive timing. Thus, cortex integrate input linearly, or place equal weight regardless their arrival time. This emergent linear...
Abstract While recent work has revealed how different inhibitory interneurons influence responses of cortical neurons to sensory stimuli, little is known about their distinct contributions perception. Here, we optogenetically activated genetically defined [parvalbumin (PV), somatostatin (SST), vasoactive intestinal peptide (VIP)] in visual cortex (V1) mice working at threshold a contrast increment detection task. The stimulus was paired with optogenetic stimulation assess enhancing V1 neuron...
Primary visual cortex (V1) in the mouse projects to numerous brain areas, including several secondary frontal cortex, and basal ganglia. While it has been demonstrated that optogenetic silencing of V1 strongly impairs visually guided behavior, is not known which downstream areas are required for behaviors. Here we trained mice perform a contrast-increment change detection task, substantial stimulus information present V1. Optogenetic responses revealed their activity even this simple task....
Cortical neurons are characterized by irregular firing and a broad distribution of rates. The balanced state model explains these observations with cancellation mean excitatory inhibitory currents, which makes fluctuations drive firing. In networks current-based synapses, the emerges dynamically if coupling is strong, i.e., number synapses per neuron K large synaptic efficacy order 1/K . When conductance-based, current suppressed when questioning applicability idea to biological neural...
The relationship between neurons' input and spiking output is central to brain computation. Studies in vitro anesthetized animals suggest that nonlinearities emerge cells' input-output (IO; activation) functions as network activity increases, yet how neurons transform inputs vivo has been unclear. Here, we characterize cortical principal activation awake mice using two-photon optogenetics. We deliver fixed at the soma while varies with sensory stimuli. find responses optogenetic are nearly...
Our brains encode many features of the sensory world into memories: we can sing along with songs have heard before, interpret spoken and written language composed words learned, recognize faces objects. Where are these memories stored? Each area cerebral cortex has a huge number local, recurrent, excitatory-excitatory synapses, as 500 million per cubic millimeter. Here I review evidence that cortical recurrent connectivity in is substrate for memories. Evidence suggests local network encodes...
Complex goal-directed behaviors extend over time and thus depend on the ability to serially order memories assemble compound, temporally coordinated movements. Theories of sequential processing range from simple associative chaining hierarchical models in which is encoded explicitly separately sequence components. To examine how short-term memory planning for sequences might be coded, we used microstimulation perturb neural activity supplementary eye field (SEF) while animals held a two cued...
Abstract. Purpose: The Gloucestershire Diabetic Eye Screening Programme offers annual digital photographic screening for diabetic retinopathy to a countywide population of people with diabetes. This study was designed investigate progression in this programme the English NHS Programme. Methods: Mydriatic retinal photographs diabetes screened on at least 2 occasions between 2005 and 2010 were graded included if classification first no DR (R0), background one (R1a) or both eyes (R1b). Times...
Combining information from multiple sources is a fundamental operation performed by networks of neurons in the brain, whose general principles are still largely unknown. Experimental evidence suggests that combination inputs cortex relies on nonlinear summation. Such nonlinearities thought to be perform complex computations. However, these non-linearities inconsistent with balanced-state model, one most popular models cortical dynamics, which predicts have linear response. This linearity...
Abstract State-of-the-art all-optical systems promise unprecedented access to neural activity in vivo , using multiphoton optogenetics allow simultaneous imaging and control of selected neurons at cellular resolution. However, achieve wide use stimulation imaging, simple strategies are needed robustly stably express opsins indicators the same cells. Here, we describe a bicistronic adeno-associated virus (AAV) that expresses both fast bright calcium indicator jGCaMP8s, soma-targeted (st)...
Abstract The relationship between neurons’ input and spiking output is central to brain computation. Studies in vitro anesthetized animals suggest nonlinearities emerge cells’ input-output (activation) functions as network activity increases, yet how neurons transform inputs vivo has been unclear. Here, we characterize cortical principal activation awake mice using two-photon optogenetics. We deliver fixed at the soma while varies with sensory stimuli. find responses optogenetic are nearly...
Abstract Brain computations depend on how neurons transform inputs to spike outputs. Here, understand input-output transformations in cortical networks, we recorded spiking responses from visual cortex (V1) of awake mice either sex while pairing sensory stimuli with optogenetic perturbation excitatory and parvalbumin-positive inhibitory neurons. We found that V1 neurons’ average were primarily additive (linear). used a recurrent network model determine whether these data, as well past...
Abstract Many cortical network models use recurrent coupling strong enough to require inhibition for stabilization. Yet it has been experimentally unclear whether inhibition-stabilized (ISN) describe function well across areas and states. Here we test several ISN predictions, including the counterintuitive (paradoxical) suppression of inhibitory firing in response optogenetic stimulation. We find clear evidence operation mouse visual, somatosensory, motor cortex. Simple two-population data...