Project description:We report RNA sequencing of single virus-infected neurons upstream of neurons producing corticotropin-releasing hormone (CRH). Analyses of PRV-infected transcriptomes reveal neurons upstream of CRH neurons express diverse and a large variety of signaling molecules. The molecular identities of upstream neurons can be used to superimpose a molecular on neuroanatomical circuit maps.
Project description:The dorsal raphe nucleus (DRN) is an important source of neuromodulators and has been implicated in a wide variety of behavioral and neurological disorders. The DRN is subdivided into distinct anatomical subregions comprised of multiple cell types, and its complex cellular organization has impeded efforts to investigate the distinct circuit and behavioral functions of its subdomains. Here we used single-cell RNA sequencing, in situ hybridization, anatomical tracing, and spatial correlation analysis to map the transcriptional and spatial profiles of cells from the mouse DRN. Our analysis of 39,411 single-cell transcriptomes revealed at least 18 distinct neuron subtypes and 5 serotonergic neuron subtypes with distinct molecular and anatomical properties, including a serotonergic neuron subtype that preferentially innervates the basal ganglia. Our study lays out the molecular organization of distinct serotonergic and non-serotonergic subsystems, and will facilitate the design of strategies for further dissection the DRN and its diverse functions.
Project description:The purpose of this protocol is to develop a detailed MRI technique and haemodynamic maps enabling early detection of colorectal metastases in the liver.
Project description:The striatum is the interface between dopamine reward signals and cortico-basal ganglia circuits that mediate diverse behavioral functions. Medium spiny neurons (MSNs) constitute the vast majority of striatal neurons and are traditionally classified as direct- or indirect-pathway neurons. However, that traditional model does not explain the anatomical and functional diversity of MSNs. Here, we defined molecularly distinct MSN types in the primate striatum, including (1) dorsal striatum MSN types associated with striosome and matrix compartments, (2) ventral striatum types associated with the nucleus accumbens shell and olfactory tubercle, and (3) an MSN-like type restricted to mu-opioid receptor rich islands in the ventral striatum. These results lay the foundation for achieving cell type-specific transgenesis in the primate striatum and provide a blueprint for investigating circuit-specific processing.
Project description:We report the characterization of a synthetic genetic circuit using RNA-Seq data. Data is collected for all input inducer combinations and cells harboring the circuit are grown in two conditions (14 ml culture tubes and 250 ml Erlenmeyer flasks).
Project description:We report the characterization of the 0x58 circuit, a modified version and wild-type cells not containing any circuit. Data is collected for all input inducer combinations and cells harboring the circuit are grown in culture tubes.
Project description:Innate social behaviors, such as mating and fighting, are fundamental to animal reproduction and survival. However, social engagements are associated with risks for the individual, such as pathogenic infection and physical injury. Little is known about the neural mechanism that allows for appropriate risk assessment and the suppression of hazardous social interactions. We have identified the posteromedial nucleus of the cortical amygdala (COApm) as a locus required for the suppression of mating with an unhealthy female and aggressive behaviors towards a dominant male intruder. Using anatomical tracing, functional imaging, and circuit-level epistatic analyses, we show that suppression of social engagements is mediated by the COApm projections onto the glutamatergic population of the medial amygdalar nucleus (MEA). We further show that this projection that governs social engagements is demarcated by expression of both the neuromodulator thyrotropin-releasing hormone (TRH) in the COApm and the TRH-receptor (TRHR) in the postsynaptic MEA glutamatergic neurons. Modulating TRH-expressing neurons as well as infusing TRHR ligand into the MEA phenocopy functional manipulation of the COApm-MEA circuit. We have, therefore, uncovered a novel neural mechanism that endows animals with the ability to modulate innate reproductive and aggressive social interactions according to the health and threat status of reciprocating individuals. Deficits in such a mechanism may lead to the spread of disease, while uncontrolled engagement may lead to pathological conditions, such as social withdrawal and depression.
Project description:Neuronal activity-dependent transcription couples sensory experience to adaptive responses of the brain including learning and memory. Mechanisms of activity-dependent gene expression including alterations of the epigenome have been characterized. However, the fundamental question of whether and how sensory experience remodels chromatin architecture in the adult brain in vivo to induce neural code transformations and learning and memory remains to be addressed. Here, in vivo calcium imaging, optogenetics, and pharmacological approaches reveal that granule neuron activation in the anterior dorsal cerebellar vermis (ADCV) plays a crucial role in a novel delay tactile startle learning paradigm in mice. Strikingly, using large-scale transcriptome and chromatin profiling, we have discovered that activation of the motor learning-linked granule neuron circuit reorganizes neuronal chromatin including through long-distance enhancer-promoter and transcriptionally active compartment interactions to orchestrate distinct granule neuron gene expression modules. Conditional CRISPR knockout of the chromatin architecture regulator Cohesin in ADCV granule neurons in adult mice disrupts activity-dependent transcription and motor learning. These findings define how sensory experience patterns chromatin architecture and neural circuit coding in the brain to drive motor learning.