Rachel Enstrom
A5021073004- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neural Engineering
- Connective tissue disorders research
- Neurogenesis and neuroplasticity mechanisms
- Mitochondrial Function and Pathology
- Visual perception and processing mechanisms
- Cardiac Valve Diseases and Treatments
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Advanced Fluorescence Microscopy Techniques
- Receptor Mechanisms and Signaling
- TGF-β signaling in diseases
- Genetic Neurodegenerative Diseases
- Aortic Disease and Treatment Approaches
Allen Institute
2020-2024
Allen Institute for Brain Science
2020-2024
University of Washington
2015-2017
Matrix Research (United States)
2015
Benaroya Research Institute
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...
Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion human neocortex marked by distinctive pyramidal neurons with extensive L1 branching, but whether interneurons are similarly diverse underexplored. Using Patch-seq recordings from neurosurgical tissue, we identified four transcriptomic subclasses mouse homologs, along distinct subtypes types...
Marfan syndrome (MFS) is caused by mutations in the gene encoding fibrillin-1 (FBN1); however, mechanisms through which deficiency causes MFS-associated aortopathy are uncertain. Recently, attention was focused on hypothesis that increased transforming growth factor-β (TGF-β) signaling aortic medial smooth muscle cells (SMC). However, there many reasons to doubt TGF-β drives aortopathy. We used a mouse model test whether SMC perturbed variant MFS and blockade of prevents aortopathy.MFS mice...
Prenatal deletion of the type II transforming growth factor-β (TGF-β) receptor (TBRII) prevents normal vascular morphogenesis and smooth muscle cell (SMC) differentiation, causing embryonic death. The role TBRII in adult SMC is less well studied. Clarification this has important clinical implications because should ablate TGF-β signaling, blockade signaling envisioned as a treatment for human aortopathies. We hypothesized that postnatal loss would cause aortopathy.We generated mice with...
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...
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 Neocortical layer 1 (L1) is a site of convergence between pyramidal neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion human neocortex marked by distinctive types with extensive branching in L1, but whether L1 interneurons are similarly diverse underexplored. Using patch-seq recordings from neurosurgically resected tissues, we identified four transcriptomically defined subclasses, unique subtypes...
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...
The distinctive physiology of striatal medium spiny neurons (MSNs) underlies their ability to integrate sensory and motor input. In rodents, MSNs have a hyperpolarized resting potential low input resistance. When activated, they delayed onset spiking regular spike rate. Here, we show that in the macaque putamen, latency is reduced rate adaptation increased relative mouse. We use whole-cell brain slice recordings recover single-cell gene expression using Patch-seq distinguish MSN cell types....
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...