Robust single-shot 3D fluorescence imaging in scattering media with a simulator-trained neural network.

Imaging through scattering is a pervasive and difficult problem in many biological applications. The high background and the exponentially attenuated target signals due to scattering fundamentally limits the imaging depth of fluorescence microscopy. Light-field systems are favorable for high-speed volumetric imaging, but the 2D-to-3D reconstruction is fundamentally ill-posed, and scattering exacerbates the condition of the inverse problem.

Targeted micro-fiber arrays for measuring and manipulating localized multi-scale neural dynamics over large, deep brain volumes during behavior.

Neural population dynamics relevant to behavior vary over multiple spatial and temporal scales across three-dimensional volumes. Current optical approaches lack the spatial coverage and resolution necessary to measure and manipulate naturally occurring patterns of large-scale, distributed dynamics within and across deep brain regions such as the striatum. We designed a new micro-fiber array approach capable of chronically measuring and optogenetically manipulating local dynamics across over 100 targeted locations simultaneously in head-fixed and freely moving mice, enabling the investigation of cell-type- and neurotransmitter-specific signals over arbitrary 3D volumes at a spatial resolution and coverage previously inaccessible.

Targeted micro-fiber arrays for measuring and manipulating localized multi-scale neural dynamics over large, deep brain volumes during behavior.

Neural population dynamics relevant for behavior vary over multiple spatial and temporal scales across 3-dimensional volumes. Current optical approaches lack the spatial coverage and resolution necessary to measure and manipulate naturally occurring patterns of large-scale, distributed dynamics within and across deep brain regions such as the striatum. We designed a new micro-fiber array and imaging approach capable of chronically measuring and optogenetically manipulating local dynamics across over 100 targeted locations simultaneously in head-fixed and freely moving mice.

Robust single-shot 3D fluorescence imaging in scattering media with a simulator-trained neural network.

Imaging through scattering is a pervasive and difficult problem in many biological applications. The high background and the exponentially attenuated target signals due to scattering fundamentally limits the imaging depth of fluorescence microscopy. Light-field systems are favorable for high-speed volumetric imaging, but the 2D-to-3D reconstruction is fundamentally ill-posed, and scattering exacerbates the condition of the inverse problem.

High-speed low-light in vivo two-photon voltage imaging of large neuronal populations.

Monitoring spiking activity across large neuronal populations at behaviorally relevant timescales is critical for understanding neural circuit function. Unlike calcium imaging, voltage imaging requires kilohertz sampling rates that reduce fluorescence detection to near shot-noise levels. High-photon flux excitation can overcome photon-limited shot noise, but photobleaching and photodamage restrict the number and duration of simultaneously imaged neurons.

The Bruce effect: Representational stability and memory formation in the accessory olfactory bulb of the female mouse.

In the Bruce effect, a mated female mouse becomes resistant to the pregnancy-blocking effect of the stud. Various lines of evidence suggest that this form of behavioral imprinting results from reduced sensitivity of the female's accessory olfactory bulb (AOB) to the stud's chemosignals. However, the AOB's combinatorial code implies that diminishing responses to one individual will distort representations of other stimuli.

Single-shot 3D wide-field fluorescence imaging with a Computational Miniature Mesoscope.

Fluorescence microscopes are indispensable to biology and neuroscience. The need for recording in freely behaving animals has further driven the development in miniaturized microscopes (miniscopes). However, conventional microscopes/miniscopes are inherently constrained by their limited space-bandwidth product, shallow depth of field (DOF), and inability to resolve three-dimensional (3D) distributed emitters.

Synchronous Infra-Slow Oscillations Organize Ensembles of Accessory Olfactory Bulb Projection Neurons into Distinct Microcircuits.

The accessory olfactory system controls social and sexual behavior. In the mouse accessory olfactory bulb, the first central stage of information processing along the accessory olfactory pathway, projection neurons (mitral cells) display infra-slow oscillatory discharge with remarkable periodicity. The physiological mechanisms that underlie this default output state, however, remain controversial.

Simultaneous multiplane imaging with reverberation two-photon microscopy.

Multiphoton microscopy has gained enormous popularity because of its unique capacity to provide high-resolution images from deep within scattering tissue. Here, we demonstrate video-rate multiplane imaging with two-photon microscopy by performing near-instantaneous axial scanning while maintaining three-dimensional micrometer-scale resolution. Our technique, termed reverberation microscopy, enables the monitoring of neuronal populations over large depth ranges and can be implemented as a simple add-on to a conventional design.

Rapid Changes in Synaptic Strength After Mild Traumatic Brain Injury.

Traumatic brain injury (TBI) affects millions of Americans annually, but effective treatments remain inadequate due to our poor understanding of how injury impacts neural function. Data are particularly limited for mild, closed-skull TBI, which forms the majority of human cases, and for acute injury phases, when trauma effects and compensatory responses appear highly dynamic. Here we use a mouse model of mild TBI to characterize injury-induced synaptic dysfunction, and examine its progression over the hours to days after trauma.

Neuronal imaging with ultrahigh dynamic range multiphoton microscopy.

Multiphoton microscopes are hampered by limited dynamic range, preventing weak sample features from being detected in the presence of strong features, or preventing the capture of unpredictable bursts in sample strength. We present a digital electronic add-on technique that vastly improves the dynamic range of a multiphoton microscope while limiting potential photodamage. The add-on provides real-time negative feedback to regulate the laser power delivered to the sample, and a log representation of the sample strength to accommodate ultrahigh dynamic range without loss of information.

Neural mechanisms of social learning in the female mouse.

Social interactions are often powerful drivers of learning. In female mice, mating creates a long-lasting sensory memory for the pheromones of the stud male that alters neuroendocrine responses to his chemosignals for many weeks. The cellular and synaptic correlates of pheromonal learning, however, remain unclear.

Neural circuit mechanisms for pattern detection and feature combination in olfactory cortex.

Odors are initially encoded in the brain as a set of distinct physicochemical characteristics but are ultimately perceived as a unified sensory object--a "smell." It remains unclear how chemical features encoded by diverse odorant receptors and segregated glomeruli in the main olfactory bulb (MOB) are assembled into integrated cortical representations. Combining patterned optical microstimulation of MOB with in vivo electrophysiological recordings in anterior piriform cortex (PCx), we assessed how cortical neurons decode complex activity patterns distributed across MOB glomeruli.

Syntaxin-4 defines a domain for activity-dependent exocytosis in dendritic spines.

Changes in postsynaptic membrane composition underlie many forms of learning-related synaptic plasticity in the brain. At excitatory glutamatergic synapses, fusion of intracellular vesicles at or near the postsynaptic plasma membrane is critical for dendritic spine morphology, retrograde synaptic signaling, and long-term synaptic plasticity. Whereas the molecular machinery for exocytosis in presynaptic terminals has been defined in detail, little is known about the location, kinetics, regulation, or molecules involved in postsynaptic exocytosis.

Genetic control of neuronal activity in mice conditionally expressing TRPV1.

Here we describe a knock-in mouse model for Cre-loxP-based conditional expression of TRPV1 in central nervous system neurons. Expression of Cre recombinase using biolistics, lentivirus or genetic intercrosses triggered heterologous expression of TRPV1 in a cell-specific manner. Application of the TRPV1 ligand capsaicin induced strong inward currents, triggered action potentials and activated stereotyped behaviors, allowing cell type-specific chemical genetic control of neuronal activity in vitro and in vivo.

In vivo light-induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2.

Channelrhodopsin-2 (ChR2) is a light-gated, cation-selective ion channel isolated from the green algae Chlamydomonas reinhardtii. Here, we report the generation of transgenic mice that express a ChR2-YFP fusion protein in the CNS for in vivo activation and mapping of neural circuits. Using focal illumination of the cerebral cortex and olfactory bulb, we demonstrate a highly reproducible, light-dependent activation of neurons and precise control of firing frequency in vivo.

Sparse and selective odor coding by mitral/tufted neurons in the main olfactory bulb.

The mammalian olfactory system recognizes an enormous variety of odorants carrying a wide range of important behavioral cues. In the main olfactory bulb (MOB), odorants are ultimately represented through the action potential activity of mitral/tufted cells (M/Ts), whose selectivity and tuning to odorant molecules are therefore fundamental determinants of MOB sensory coding. However, the sheer number and diversity of discrete olfactory stimuli has been a major barrier to comprehensively evaluating M/T selectivity.

Dopamine inhibits mitral/tufted--> granule cell synapses in the frog olfactory bulb.

Synaptic interactions between the dendrites of mitral/tufted (MT) and granule cells (GCs) in the olfactory bulb are important for the determination of spatiotemporal firing patterns of MTs, which form an odor representation passed to higher brain centers. These synapses are subject to modulation from several sources originating both within and outside the bulb. We show that dopamine, presumably released by TH-positive local interneurons, reduces synaptic transmission from MTs to GCs.