A5015371539- Neuroscience and Neuropharmacology Research
- Neurological disorders and treatments
- Genetic Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Photoreceptor and optogenetics research
- Retinal Development and Disorders
- Biochemical Analysis and Sensing Techniques
- Nuclear Receptors and Signaling
- Advanced Fluorescence Microscopy Techniques
- Photochromic and Fluorescence Chemistry
- Olfactory and Sensory Function Studies
- Receptor Mechanisms and Signaling
- RNA Research and Splicing
- Neuroscience and Neural Engineering
- Ion channel regulation and function
- Genetics and Neurodevelopmental Disorders
- Advanced Proteomics Techniques and Applications
- Phagocytosis and Immune Regulation
- Neurobiology and Insect Physiology Research
Van Andel Institute
2024
Northwestern University
2018-2023
Lurie Children's Hospital
2022
University of Vermont
2014
Within the basal ganglia circuit, external globus pallidus (GPe) is critically involved in motor control. Aside from Foxp2 + neurons and ChAT that have been established as unique neuron types, there little consensus on classification of GPe neurons. Properties remaining types are poorly defined. In this study, we leverage new mouse lines, viral tools, molecular markers to better define subtypes. We found Sox6 represents a novel, defining marker for Lhx6 lack expression were devoid both...
We have previously established that PV + neurons and Npas1 are distinct neuron classes in the external globus pallidus (GPe): they different topographical, electrophysiological, circuit, functional properties. Aside from Foxp2 neurons, which a unique subclass within class, we lack driver lines effectively capture other GPe subclasses. In this study, examined utility of Kcng4-Cre, Npr3-Cre, Npy2r-Cre mouse (both males females) for delineation subtypes. By using these novel lines, provided...
KCNT1 encodes the sodium-activated potassium channel KNa1.1, expressed preferentially in frontal cortex, hippocampus, cerebellum, and brainstem. Pathogenic missense variants are associated with intractable epilepsy, namely epilepsy of infancy migrating focal seizures (EIMFS), sleep-related hypermotor (SHE). In vitro studies pathogenic support predominantly a gain-of-function molecular mechanism, but how these behave neuron or ultimately drive formation an epileptogenic circuit is important...
Recent developments in intersectional strategies have greatly advanced our ability to precisely target brain cell types based on unique co-expression patterns. To accelerate the application of genetics, we perform a brain-wide characterization 13 Flp and tTA mouse driver lines selected seven for further analysis expression vesicular neurotransmitter transporters. Using selective Cre lines, created more than 10 Cre/tTA combinational type targeting circuit analysis. We then used...
Abstract LRRK2 mutations are closely associated with Parkinson’s disease (PD). Convergent evidence suggests that regulates striatal function. Here, by using knock-in mouse lines expressing the two most common pathogenic mutations—G2019S and R1441C—we investigated how altered physiology. While we found both R1441C G2019S mice displayed reduced nigrostriatal dopamine release, hypoexcitability in indirect-pathway projection neurons, alterations an impaired striatal-dependent motor learning were...
The mammalian retina harbors over 100 different cell types. To understand how retinal circuits work, it is essential to systematically access each type. A widely used approach for achieving targeted transgene expression exploits promoter-driven Cre lines. However, in a given transgenic line the and elsewhere brain rarely confined single type, contributing ambiguity interpretation of results from broadly applied manipulations. obtain unambiguous information about processing, desirable have...
The primary motor cortex (M1) integrates sensory and cognitive inputs to generate voluntary movement. Its functional impairments have been implicated in the pathophysiology of symptoms Parkinson's disease (PD). Specifically, dopaminergic degeneration basal ganglia dysfunction entrain M1 neurons into abnormally synchronized bursting pattern activity throughout cortico-basal ganglia-thalamocortical network. However, how midbrain affects anatomy, microcircuit connectivity, function network...
Abstract We have previously established that PV + neurons and Npas1 are distinct neuron classes in the GPe— they different topographical, electrophysiological, circuit, functional properties. Aside from Foxp2 neurons, which a unique subclass within class, we lack driver lines effectively capture other GPe subclasses. In this study, examined utility of Kcng4-Cre, Npr3-Cre, Npy2r-Cre mouse (both males females) for delineation subtypes. By using these novel lines, provided most exhaustive...
Abstract LRRK2 mutations are associated with both familial and sporadic forms of Parkinson’s disease (PD). Convergent evidence suggests that plays critical roles in regulating striatal function. Here, by using knock-in mouse lines express the two most common pathogenic mutations—G2019S R1441C—we investigated how altered physiology. We found R1441C mice displayed a reduced nigrostriatal dopamine release hypoexcitability indirect-pathway projection neurons. These alterations were an impaired...
Neural computations arise from highly precise connections between specific types of neurons. Retinal ganglion cells (RGCs) with similar stratification patterns are positioned to receive inputs but often display different response properties. In this study, we used intersectional mouse genetics achieve single-cell type labeling and identified an object motion sensitive (OMS) AC type, COMS-AC(counter-OMS AC). Optogenetic stimulation revealed that COMS-AC makes glycinergic synapses the...
Abstract Striatal dysfunction is implicated in many forms of dystonia, including idiopathic, inherited and iatrogenic dystonias. The striatum comprised largely GABAergic spiny projection neurons (SPNs) that are defined by their long-range efferents. Direct SPNs (dSPNs) project to the internal globus pallidus/substantia nigra reticulata whereas indirect pathway (iSPNs) external pallidum; concerted activity both SPN subtypes modulates movement. Convergent results from genetic, imaging...
Target derived factors influence the specification, maintenance, and modulation of synaptic connectivity. The transmembrane protein, Kit Ligand, receptor tyrosine kinase are differentially expressed in connected neurons. In development postnatal periods, these proteins maintain connectivity between cerebellar Purkinje cells (PC) that express presynaptic Molecular Layer Interneurons (MLI) expressing Kit. this study, it is demonstrated Stem Cell Factor (SCF), active extracellular domain...
Abstract Within the basal ganglia circuit, external globus pallidus (GPe) is critically involved in motor control. Aside from Foxp2 + neurons and ChAT that have been established as unique neuron types, there little consensus on classification of GPe neurons. Properties remaining types are poorly-defined. In this study, we leverage new mouse lines, viral tools, molecular markers to better define subtypes. We found Sox6 represents a novel, defining marker for Lhx6 lack expression were devoid...