Michelle Maxwell
A5033291005- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Cell Image Analysis Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Single-cell and spatial transcriptomics
- Neuroscience and Neural Engineering
- Mitochondrial Function and Pathology
- Cholinesterase and Neurodegenerative Diseases
- Sirtuins and Resveratrol in Medicine
- Advanced Fluorescence Microscopy Techniques
- RNA Research and Splicing
- Visual perception and processing mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Genetic Neurodegenerative Diseases
Allen Institute
2020-2023
Allen Institute for Brain Science
2020-2023
Harvard University
2015
Massachusetts General Hospital
2015
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...
Abstract The neocortex is disproportionately expanded in human compared with mouse 1,2 , both its total volume relative to subcortical structures and the proportion occupied by supragranular layers composed of neurons that selectively make connections within other telencephalic structures. Single-cell transcriptomic analyses show an increased diversity glutamatergic neuron types pronounced gradients as a function cortical depth 3 . Here, probe functional anatomical correlates this diversity,...
Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid-producing (GABAergic) neurons from subclasses to high diversity more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology single-cell RNA sequencing) sampling in human brain slices was used reliably target and analyze individual This characterization elucidated transitions between PVALB SST subclasses, morphological heterogeneity within...
Sirtuin deacetylases regulate diverse cellular pathways and influence disease processes. Our previous studies identified the brain-enriched sirtuin-2 (SIRT2) deacetylase as a potential drug target to counteract neurodegeneration. In present study, we characterize SIRT2 inhibition activity of brain-permeable compound AK7 examine efficacy this small molecule in models Parkinson's disease, amyotrophic lateral sclerosis cerebral ischemia. results demonstrate that is neuroprotective disease; it...
Abstract Neurons are frequently classified into distinct groups or cell types on the basis of structural, physiological, genetic attributes. To better constrain definition neuronal types, we characterized transcriptomes and intrinsic physiological properties over 3,700 GABAergic mouse visual cortical neurons reconstructed local morphologies 350 those neurons. We found that most transcriptomic (t-types) occupy specific laminar positions within cortex, many t-types exhibit consistent...
The neocortex is disproportionately expanded in human compared to mouse, both its total volume relative subcortical structures and the proportion occupied by supragranular layers that selectively make connections within cortex other telencephalic structures. Single-cell transcriptomic analyses of mouse show an increased diversity glutamatergic neuron types pronounced gradients as a function cortical depth. To probe functional anatomical correlates this diversity, we describe robust Patch-seq...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motor neuron disorder. Genetic studies have linked mutation of the gene SOD1 to ALS pathology as well several other pathological processes including modulation glutamatergic function and inflammatory processes. Since therapeutic approaches for are focused on function, we investigated glutamate transport based its receptor excitotoxicity-induced response. In vivo positron emission tomography (PET) imaging metabotropic...
The mammalian brain is composed of diverse neuron types that play different functional roles. Recent single-cell RNA sequencing approaches have led to a whole taxonomy transcriptomically-defined cell types, yet type definitions include multiple cellular properties can offer additional insights into neuron's role in circuits. While the Patch-seq method investigate how transcriptomic relate local morphological and electrophysiological linking identities long-range projections major unresolved...
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 Human cortical interneurons have been challenging to study due high diversity and lack of mature brain tissue platforms genetic targeting tools. We employed rapid GABAergic neuron viral labeling plus unbiased Patch-seq sampling in slices define the signature morpho-electric properties neurons human neocortex. Viral greatly facilitated SST subclass, including primate specialized double bouquet cells which mapped two transcriptomic types. Multimodal analysis uncovered an type with...
Abstract Identification of the structural connections between neurons is a prerequisite to understanding brain function. We developed pipeline systematically map brain-wide monosynaptic inputs specific neuronal populations using Cre-driver mouse lines and recombinant rabies tracing system. first improved virus strategy accurately identify starter cells efficiently quantify presynaptic inputs. then mapped different excitatory inhibitory neuron subclasses in primary visual cortex seven higher...
Neurons are frequently classified into distinct groups or cell types on the basis of structural, physiological, genetic attributes. To better constrain definition neuronal types, we characterized transcriptomes and intrinsic physiological properties over 3,700 GABAergic mouse visual cortical neurons reconstructed local morphologies 350 those neurons. We found that most transcriptomic (t-types) occupy specific laminar positions within cortex, many t-types exhibit consistent...
Abstract Identification of the structural connections between neurons is a prerequisite to understanding brain function. We developed pipeline systematically map brain-wide monosynaptic inputs specific neuronal populations using Cre-driver mouse lines and recombinant rabies tracing system. first improved virus strategy accurately identify starter cells efficiently quantify presynaptic inputs. then mapped different excitatory inhibitory neuron subclasses in primary visual cortex seven higher...