A5054988373- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA regulation and disease
- Neurogenesis and neuroplasticity mechanisms
- Immune cells in cancer
- Neuroscience and Neural Engineering
- Memory and Neural Mechanisms
- Virus-based gene therapy research
- Receptor Mechanisms and Signaling
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Axon Guidance and Neuronal Signaling
- Developmental Biology and Gene Regulation
- Neurobiology and Insect Physiology Research
- Reproductive Physiology in Livestock
- Animal Diversity and Health Studies
- Advanced Memory and Neural Computing
- Advanced Fluorescence Microscopy Techniques
- Reproductive System and Pregnancy
- Biochemical Analysis and Sensing Techniques
- Visual perception and processing mechanisms
- RNA modifications and cancer
- Cell Image Analysis Techniques
Broad Institute
2019-2024
Harvard University
2019-2024
King Abdullah University of Science and Technology
2019-2024
Boston VA Research Institute
2021-2024
Harvard University Press
2024
New York University Abu Dhabi
2024
New York University
2024
Allen Institute
2024
Allen Institute for Brain Science
2024
Stanley Foundation
2023
Abstract Defense against environmental threats is essential for animal survival. However, the neural circuits responsible transforming unconditioned sensory stimuli and generating defensive behaviours remain largely unclear. Here, we show that corticofugal neurons in auditory cortex (ACx) targeting inferior colliculus (IC) mediate an innate, sound-induced flight behaviour. Optogenetic activation of these neurons, or their projection terminals IC, sufficient initiating responses, while...
Cortical inhibitory circuits play important roles in shaping sensory processing. In auditory cortex, however, functional properties of genetically identified neurons are poorly characterized. By two-photon imaging-guided recordings, we specifically targeted 2 major types cortical neuron, parvalbumin (PV) and somatostatin (SOM) expressing neurons, superficial layers mouse cortex. We found that PV cells exhibited broader tonal receptive fields with lower intensity thresholds stronger...
SUMMARY In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools access manipulate fine subtypes are still limited. Here, performed systematic analysis single cell genomic data identify enhancer candidates for each cortical interneuron subtypes. We established set enhancer-AAV that highly specific distinct populations striatal cholinergic neurons....
Despite accounting for about 20% of all the layer 2/3 inhibitory interneurons, vasoactive intestinal polypeptide (VIP) expressing neurons remain least thoroughly studied major subtypes. In recent studies, VIP have been shown to be activated by a variety cortico-cortical and neuromodulatory inputs, but their basic sensory response properties poorly characterized. We set out explore functional in primary visual (V1) auditory cortex (A1), using two-photon imaging guided patch recordings. found...
Orientation selectivity (OS) in the visual cortex has been found to be invariant increases stimulus contrast, a finding that cannot accounted for by original, purely excitatory Hubel and Wiesel model. This property of OS may important preserving quality perceived across range intensity. The synaptic mechanisms can prevent broadening caused contrast-dependent strengthening inputs cortical neurons remain unknown. Using vivo loose-patch recordings, we layer 4 mouse primary (V1) spike response...
Corticofugal projections from the primary auditory cortex (A1) have been shown to play a role in modulating subcortical processing. However, functional properties of corticofugal neurons and their synaptic circuitry mechanisms remain unclear. In this study, we performed vivo whole-cell recordings layer 5 (L5) pyramidal rat A1 found two distinct neuronal classes according properties. Intrinsic-bursting (IB) neurons, L5 exhibited early rather unselective spike responses wide range frequencies....
During the development of periphery auditory circuits, spiral ganglion neurons (SGNs) extend their neurites to innervate cochlear hair cells (HCs) with soma aggregated into a cluster spatially segregated from sensory epithelium. The molecular mechanisms underlying this spatial patterning remain unclear. In study, in situ hybridization mouse cochlea suggests that Slit2 and its receptor, Robo1/2, exhibit apparently complementary expression patterns nearby region, limbus. Robo1/2 mutants,...
Microglia play a key role in shaping the formation and refinement of excitatory network brain. However, less is known about whether how they organize development distinct inhibitory networks. We find that microglia are essential for proper somatostatin-positive (SST+) cell synapses during second postnatal week. further identify pair molecules act antagonistically to one another organization SST+ axonal elaboration. Whereas CX3CL1 acts suppress growth complexity, CXCL12 promotes it. Assessing...
Somatostatin interneurons are the earliest born population of cortical inhibitory cells. They crucial to support normal brain development and function; however, mechanisms underlying their integration into nascent circuitry not well understood. In this study, we begin by demonstrating that maturation somatostatin in mouse somatosensory cortex is activity dependent. We then investigated relationship between activity, alternative splicing, synapse formation within population. Specifically,...
Retinal waves represent an early form of patterned spontaneous neural activity in the visual system. These originate retina before eye-opening and propagate throughout system, influencing assembly maturation subcortical brain regions. However, because it is technically challenging to ablate retina-derived cortical without inducing compensatory activity, role these play development cortex remains unclear. To address this question, we used targeted conditional genetics disrupt cholinergic...
During the development of periphery auditory circuitry, spiral ganglion neurons (SGNs) form a spatially precise pattern innervation cochlear hair cells (HCs), which is an essential structural foundation for central processing. However, molecular mechanisms underlying developmental formation this remain not well understood. Here, we specifically examined involvement Eph family members in development. By performing RNA-sequencing different types cell, situ hybridization, and...
Neurogliaform cells are a distinct type of GABAergic cortical interneurons known for their volume transmission output property. However, activity and function within circuits remain unclear. Here, we developed two genetic tools to target these neurons examine in the primary visual cortex. We found that spontaneous neurogliaform positively correlated with locomotion. Silencing increased during locomotion impaired responses L2/3 pyramidal neurons. Furthermore, contrast-dependent response...
Recent success in identifying gene regulatory elements the context of recombinant adeno-associated virus vectors have enabled cell type-restricted expression. However, within cerebral cortex these tools are presently limited to broad classes neurons. To overcome this limitation, we developed a strategy that led identification multiple novel enhancers target functionally distinct neuronal subtypes. By investigating landscape disease Scn1a, identified breadth its expression, including two...
Elucidating axonal and dendritic projection patterns of individual neurons is a key for understanding the cytoarchitecture neural circuits in brain. This requires genetic approaches to achieve Golgi-like sparse labeling desired types neurons. Here, we explored novel strategy stochastic gene activation with regulated sparseness (STARS), which choice between 2 competing Cre-lox recombination events controlled by varying lox efficiency cassette length. In created STARS transgenic mouse crossed...
<title>Abstract</title> Neurogliaform cells are a distinct type of GABAergic cortical interneurons known for their ‘volume transmission’ output property. However, activity and function within circuits remain unclear. Here, we developed two genetic tools to target these neurons examine in the primary visual cortex. We found that spontaneous neurogliaform positively correlated with locomotion. Silencing increased during locomotion impaired responses L2/3 pyramidal neurons. Furthermore,...