- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- Advanced Fluorescence Microscopy Techniques
- Ion channel regulation and function
- Neurobiology and Insect Physiology Research
- Gene Regulatory Network Analysis
- CRISPR and Genetic Engineering
- stochastic dynamics and bifurcation
- Single-cell and spatial transcriptomics
- Biochemical Analysis and Sensing Techniques
- Olfactory and Sensory Function Studies
Allen Institute
2017-2022
Allen Institute for Brain Science
2017-2022
National Institute of Neurological Disorders and Stroke
2016
National Institutes of Health
2015-2016
Washington University in St. Louis
2009-2012
We present a unique, extensive, and open synaptic physiology analysis platform dataset. Through its application, we reveal principles that relate cell type to properties intralaminar circuit organization in the mouse human cortex. The dynamics of excitatory synapses align with postsynaptic subclass, whereas inhibitory synapse partly presynaptic subclass but considerable overlap. Synaptic are heterogeneous most subclass-to-subclass connections. two main axes heterogeneity strength...
Generating a comprehensive description of cortical networks requires large-scale, systematic approach. To that end, we have begun pipeline project using multipatch electrophysiology, supplemented with two-photon optogenetics, to characterize connectivity and synaptic signaling between classes neurons in adult mouse primary visual cortex (V1) human cortex. We focus on producing results detailed enough for the generation computational models enabling comparison future studies. Here, report our...
Understanding cortical microcircuits requires thorough measurement of physiological properties synaptic connections formed within and between diverse subclasses neurons. Towards this goal, we combined spatially precise optogenetic stimulation with multicellular recording to deeply characterize intralaminar translaminar monosynaptic supragranular (L2/3) neurons in the mouse visual cortex. The reliability specificity multiphoton were measured across multiple Cre lines, measurements...
We report a novel coupled system of sodium-activated potassium currents ( I KNa ) and persistent sodium NaP ), the components which are widely distributed throughout brain. Its existence importance has not been previously recognized. Although was known to exist in many cell types, source Na + activates remained mystery. now show single membrane patches generated from somas rat neurons that influx through is sufficient for activation K channels, without substantial contribution transient...
Principal neurons of the medial superior olive (MSO) convey azimuthal sound localization cues through modulation their rate action potential firing. Previous intracellular studies in vitro have shown that potentials appear highly attenuated at soma MSO neurons, potentially reflecting specialized initiation and/or a physically distant site generation. To examine this more directly, we made dual patch-clamp recordings from principal gerbil brainstem slices. Using somatic and dendritic...
Substantia nigra dopamine neurons fire tonically resulting in action potential backpropagation and dendritic Ca(2+) influx. Using imaging acute mouse brain slices, we find a surprisingly steep relationship between tonic firing rate Ca(2+). Increasing the from 1 to 6 Hz generated signals up fivefold greater than predicted by linear summation of single spike-evoked Ca(2+)-transients. This "Ca(2+) supralinearity" was produced largely depolarization interspike voltage leading activation...
Abstract Defining a complete set of cell types within the cortex requires reconciling disparate results achieved through diverging methodologies. To address this correspondence problem, multiple methodologies must be applied to same cells across single-cell experiments. Here we present new approach applying spatial transcriptomics using multiplexed fluorescence in situ hybridization, (mFISH) brain tissue previously interrogated two photon optogenetic mapping synaptic connectivity. This can...
Abstract To elucidate cortical microcircuit structure and synaptic properties we present a unique, extensive, public physiology dataset analysis platform. Through its application, reveal principles that relate cell type to synapse intralaminar circuit organization in the mouse human cortex. The dynamics of excitatory synapses align with postsynaptic subclass, whereas inhibitory partly presynaptic subclass but considerable overlap. Despite these associations, are heterogeneous most...
Abstract Generating a comprehensive description of cortical networks requires large-scale, systematic approach. To that end, the Allen Institute is engaged in pipeline project using multipatch electrophysiology, supplemented with 2-photon optogenetics, to characterize connectivity and synaptic signaling between classes neurons adult mouse human cortex. We focus on producing results detailed enough for generation computational models enabling comparison future studies. Here we report our...
Little is known about the density and function of dendritic spines on midbrain dopamine neurons, or relative contribution spine shaft synapses to excitability. Using Ca(2+) imaging, glutamate uncaging, fluorescence recovery after photobleaching transgenic mice expressing labeled PSD-95, we comparatively analyzed electrical signaling in neurons. Dendritic were present dopaminergic neurons at low densities live fixed tissue. Uncaging-evoked potential amplitudes correlated inversely with length...
SUMMARY Modern genetic approaches are powerful in providing access to diverse types of neurons within the mammalian brain and greatly facilitating study their function. We here report a large set driver reporter transgenic mouse lines, including 23 new lines targeting variety cortical subcortical cell populations 26 expressing an array molecular tools. In particular, we describe TIGRE2.0 platform introduce Cre-dependent that enable optical physiology, optogenetics, sparse labeling...
Modern genetic approaches are powerful in providing access to diverse types of neurons within the mammalian brain and greatly facilitating study their function. We here report a large set driver reporter transgenic mouse lines, including 23 new lines targeting variety cortical subcortical cell populations 26 expressing an array molecular tools. In particular, we describe TIGRE2.0 platform introduce Cre-dependent that enable optical physiology, optogenetics, sparse labeling...
Abstract The most common synaptic connections between neurons in different cortical layers form the basis of canonical microcircuit. Understanding function will require further development and application methods to efficiently characterize within outside pathway. Accordingly, we measured inputs onto superficial excitatory response sequential two-photon optogenetic stimulation deeper layers. Layer 4 somatostatin-neurons layer 2/3 represented sources input. Although from 5 were less common,...