Molecular and Anatomical Characterization of Parabrachial Neurons and Their Axonal Projections
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE207708 | GEO | 2022/07/15
REPOSITORIES: GEO
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Project description:Molecular and Anatomical Characterization of Parabrachial Neurons and Their Axonal Projections
| PRJNA856767 | ENA
Project description:The parabrachial nucleus (PBN) is a major hub that receives sensory information from both internal and external environments. Specific populations of PBN neurons are involved in behaviors including food and water intake, nociceptive responses, breathing regulation, as well as learning and responding appropriately to threatening stimuli. However, it is unclear how many PBN neuron populations exist and how different behaviors may be encoded by unique signaling molecules or receptors. Here we provide a repository of data on the molecular identity, spatial location, and projection patterns of dozens of PBN neuron subclusters. Using single-cell RNA sequencing, we identified 21 subclusters of neurons in the PBN and neighboring regions. Multiplexed in situ hybridization showed many of these subclusters are enriched within specific PBN subregions with scattered cells in several other regions. We also provide detailed visualization of the axonal projections from 21 Cre-driver lines of mice. These results are all publicly available for download and provide a foundation for further interrogation of PBN functions and connections.
| S-EPMC9668336 | biostudies-literature
Project description:Calca-expressing neurons in the parabrachial nucleus (PBN) play a major role in regulating appetite and transmitting real or potential threat signals. Here, we reveal transcripts specific or highly enriched in this neuronal population by using mouse genetics and a conditional viral ribosome-tagging approach to phenotype these neurons.
2022-07-02 | GSE207153 | GEO
Project description:How neurons connect to form functional circuits is central to the understanding of the development and function of the nervous system. In the somatosensory system, perception of sensory stimuli to the head requires specific connections between trigeminal sensory neurons and their many target areas in the central nervous system. Different trigeminal subtypes have specialized functions and downstream circuits, but it has remained unclear how subtype-specific axonal projection patterns are formed. Using zebrafish as a model system, we followed the development of two trigeminal sensory neuron subtypes: one that expresses trpa1b, a nociceptive channel important for sensing environmental chemicals; and a distinct subtype labeled by an islet1 reporter (Isl1SS). We found that Trpa1b and Isl1SS neurons have overall similar axon trajectories but different branching morphologies and distributions of presynaptic sites. Compared with Trpa1b neurons, Isl1SS neurons display reduced branch growth and synaptogenesis at the hindbrain-spinal cord junction. The subtype-specific morphogenesis of Isl1SS neurons depends on the guidance receptor Robo2. robo2 is preferentially expressed in the Isl1SS subset and inhibits branch growth and synaptogenesis. In the absence of Robo2, Isl1SS afferents acquire many of the characteristics of Trpa1b afferents. These results reveal that subtype-specific activity of Robo2 regulates subcircuit morphogenesis in the trigeminal sensory system.
| S-EPMC3252355 | biostudies-literature
Project description:Alzheimer’s disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus – brain regions where neurofibrillary inclusions and neuronal loss occur early and late in AD, respectively – from individuals spanning the neuropathological progression of AD. We identified RORB as a marker of selectively vulnerable excitatory neurons in the entorhinal cortex, and subsequently validated their depletion and selective susceptibility to neurofibrillary inclusions during disease progression using quantitative neuropathological methods. We also discovered an astrocyte subpopulation, likely representing reactive astrocytes, characterized by decreased expression of genes involved in homeostatic functions. Our characterization of selectively vulnerable neurons in AD paves the way for future mechanistic studies of selective vulnerability and potential therapeutic strategies for enhancing neuronal resilience. The brain tissue used in this study were sourced from the Biobank for Aging Studies (LIM-22) in the Department of Pathology at the University of Sao Paulo, as well as from the Neurodegenerative Diseases Brain Bank in the Memory and Aging Center at the University of California, San Francisco. Detailed neuropathological, clinical and genetic data are available under request. Please contact gerolab@gmail.com and lea.grinberg@ucsf.edu.
2020-04-05 | GSE147528 | GEO
Project description:Computational models of neural networks can be based on a variety of different parameters. These parameters include, for example, the 3d shape of neuron layers, the neurons' spatial projection patterns, spiking dynamics and neurotransmitter systems. While many well-developed approaches are available to model, for example, the spiking dynamics, there is a lack of approaches for modeling the anatomical layout of neurons and their projections. We present a new method, called Parametric Anatomical Modeling (PAM), to fill this gap. PAM can be used to derive network connectivities and conduction delays from anatomical data, such as the position and shape of the neuronal layers and the dendritic and axonal projection patterns. Within the PAM framework, several mapping techniques between layers can account for a large variety of connection properties between pre- and post-synaptic neuron layers. PAM is implemented as a Python tool and integrated in the 3d modeling software Blender. We demonstrate on a 3d model of the hippocampal formation how PAM can help reveal complex properties of the synaptic connectivity and conduction delays, properties that might be relevant to uncover the function of the hippocampus. Based on these analyses, two experimentally testable predictions arose: (i) the number of neurons and the spread of connections is heterogeneously distributed across the main anatomical axes, (ii) the distribution of connection lengths in CA3-CA1 differ qualitatively from those between DG-CA3 and CA3-CA3. Models created by PAM can also serve as an educational tool to visualize the 3d connectivity of brain regions. The low-dimensional, but yet biologically plausible, parameter space renders PAM suitable to analyse allometric and evolutionary factors in networks and to model the complexity of real networks with comparatively little effort.
| S-EPMC4164034 | biostudies-literature
Project description:Functional diversity of midbrain dopamine (DA) neurons ranges across multiple scales, from differences in intrinsic properties and connectivity to selective task engagement in behaving animals. Distinct in vitro biophysical features of DA neurons have been associated with different axonal projection targets. However, it is unknown how this translates to different firing patterns of projection-defined DA subpopulations in the intact brain. We combined retrograde tracing with single-unit recording and labelling in mouse brain to create an in vivo functional topography of the midbrain DA system. We identified differences in burst firing among DA neurons projecting to dorsolateral striatum. Bursting also differentiated DA neurons in the medial substantia nigra (SN) projecting either to dorsal or ventral striatum. We found differences in mean firing rates and pause durations among ventral tegmental area (VTA) DA neurons projecting to lateral or medial shell of nucleus accumbens. Our data establishes a high-resolution functional in vivo landscape of midbrain DA neurons.
| S-EPMC6791716 | biostudies-literature
Project description:Study objectivesThe pedunculopontine tegmental (PPT) nucleus is implicated in many brain functions, ranging from sleep/wake control and locomotion, to reward mechanisms and learning. The PPT contains cholinergic, GABAergic, and glutamatergic neurons with extensive ascending and descending axonal projections. Glutamatergic PPT (PPTvGlut2) neurons are thought to promote wakefulness, but the mechanisms through which this occurs are unknown. In addition, some researchers propose that PPTvGlut2 neurons promote locomotion, yet even though the PPT is a target for deep brain stimulation in Parkinson's disease, the role of the PPT in locomotion is debated. We hypothesized that PPTvGluT2 neurons drive arousal and specific waking behaviors via certain projections and modulate locomotion via others.MethodsWe mapped the axonal projections of PPTvGlut2 neurons using conditional anterograde tracing and then photostimulated PPTvGlut2 soma or their axon terminal fields across sleep/wake states and analyzed sleep/wake behavior, muscle activity, and locomotion in transgenic mice.ResultsWe found that stimulation of PPTvGlut2 soma and their axon terminals rapidly triggered arousals from non-rapid eye movement sleep, especially with activation of terminals in the basal forebrain (BF) and lateral hypothalamus (LH). With photoactivation of PPTvGlut2 terminals in the BF and LH, this wakefulness was accompanied by locomotion and other active behaviors, but stimulation of PPTvGlut2 soma and terminals in the substantia nigra triggered only quiet wakefulness without locomotion.ConclusionsThese findings demonstrate the importance of the PPTvGluT2 neurons in driving various aspects of arousal and show that heterogeneous brain nuclei, such as the PPT, can promote a variety of behaviors via distinct axonal projections.
| S-EPMC9742893 | biostudies-literature
Project description:Conventional neuroanatomical, immunohistochemical techniques, and electrophysiological recording, as well as in vitro labeling methods may fail to detect long range extra-neurohypophyseal-projecting axons from vasopressin (AVP)-containing magnocellular neurons (magnocells) in the hypothalamic paraventricular nucleus (PVN). Here, we used in vivo extracellular recording, juxtacellular labeling, post-hoc anatomo-immunohistochemical analysis and camera lucida reconstruction to address this question. We demonstrate that all well-labeled AVP immunopositive neurons inside the PVN possess main axons joining the tract of Greving and multi-axon-like processes, as well as axonal collaterals branching very near to the somata, which project to extra-neurohypophyseal regions. The detected regions in this study include the medial and lateral preoptical area, suprachiasmatic nucleus (SCN), lateral habenula (LHb), medial and central amygdala and the conducting systems, such as stria medullaris, the fornix and the internal capsule. Expression of vesicular glutamate transporter 2 was observed in axon-collaterals. These results, in congruency with several previous reports in the literature, provided unequivocal evidence that AVP magnocells have an uncommon feature of possessing multiple axon-like processes emanating from somata or proximal dendrites. Furthermore, the long-range non-neurohypophyseal projections are more common than an "occasional" phenomenon as previously thought.
| S-EPMC4593857 | biostudies-literature
Project description:we used technique that allows the molecular characterization of particular neuronal subpopulations based on their neuroanatomical projections and the locations of their cell bodies. This ‘retro-TRAP’ (translating ribosome affinity purification from retrogradely labeled neurons) approach relies on viral injection into an anatomical area targeted by the neurons of interest, followed by selective precipitation of ribosomes from retrogradely labeled cell bodies, and subsequent RNAseq analysis.
2018-11-01 | GSE115526 | GEO