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Trends in Neurosciences May 2018The parabrachial nucleus (PBN), which is located in the pons and is dissected by one of the major cerebellar output tracks, is known to relay sensory information... (Review)
Review
The parabrachial nucleus (PBN), which is located in the pons and is dissected by one of the major cerebellar output tracks, is known to relay sensory information (visceral malaise, taste, temperature, pain, itch) to forebrain structures including the thalamus, hypothalamus, and extended amygdala. The availability of mouse lines expressing Cre recombinase selectively in subsets of PBN neurons and viruses for Cre-dependent gene expression is beginning to reveal the connectivity and functions of PBN component neurons. This review focuses on PBN neurons expressing calcitonin gene-related peptide (CGRP) that play a major role in regulating appetite and transmitting real or potential threat signals to the extended amygdala. The functions of other specific PBN neuronal populations are also discussed. This review aims to encourage investigation of the numerous unanswered questions that are becoming accessible.
Topics: Animals; Calcitonin Gene-Related Peptide; Humans; Neurons; Parabrachial Nucleus
PubMed: 29703377
DOI: 10.1016/j.tins.2018.03.007 -
Neuron Sep 2019Sleep is crucial for our survival, and many diseases are linked to long-term poor sleep quality. Before we can use sleep to enhance our health and performance and...
Sleep is crucial for our survival, and many diseases are linked to long-term poor sleep quality. Before we can use sleep to enhance our health and performance and alleviate diseases associated with poor sleep, a greater understanding of sleep regulation is necessary. We have identified a mutation in the β-adrenergic receptor gene in humans who require fewer hours of sleep than most. In vitro, this mutation leads to decreased protein stability and dampened signaling in response to agonist treatment. In vivo, the mice carrying the same mutation demonstrated short sleep behavior. We found that this receptor is highly expressed in the dorsal pons and that these ADRB1 neurons are active during rapid eye movement (REM) sleep and wakefulness. Activating these neurons can lead to wakefulness, and the activity of these neurons is affected by the mutation. These results highlight the important role of β-adrenergic receptors in sleep/wake regulation.
Topics: Animals; Gene Knock-In Techniques; Humans; Mice; Mutation; Neurons; Pedigree; Pontine Tegmentum; Receptors, Adrenergic, beta-1; Sleep; Sleep Wake Disorders; Sleep, REM; Wakefulness
PubMed: 31473062
DOI: 10.1016/j.neuron.2019.07.026 -
Nature Reviews. Neuroscience Nov 2020The locus coeruleus (LC), or 'blue spot', is a small nucleus located deep in the brainstem that provides the far-reaching noradrenergic neurotransmitter system of the... (Review)
Review
The locus coeruleus (LC), or 'blue spot', is a small nucleus located deep in the brainstem that provides the far-reaching noradrenergic neurotransmitter system of the brain. This phylogenetically conserved nucleus has proved relatively intractable to full characterization, despite more than 60 years of concerted efforts by investigators. Recently, an array of powerful new neuroscience tools have provided unprecedented access to this elusive nucleus, revealing new levels of organization and function. We are currently at the threshold of major discoveries regarding how this tiny brainstem structure exerts such varied and significant influences over brain function and behaviour. All LC neurons receive inputs related to autonomic arousal, but distinct subpopulations of those neurons can encode specific cognitive processes, presumably through more specific inputs from the forebrain areas. This ability, combined with specific patterns of innervation of target areas and heterogeneity in receptor distributions, suggests that activation of the LC has more specific influences on target networks than had initially been imagined.
Topics: Animals; Cognition; Humans; Locus Coeruleus; Neural Pathways; Neuronal Plasticity; Neurons; Nucleus Accumbens
PubMed: 32943779
DOI: 10.1038/s41583-020-0360-9 -
ELife Nov 2022The parabrachial nucleus (PBN) is a major hub that receives sensory information from both internal and external environments. Specific populations of PBN neurons are...
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.
Topics: Animals; Mice; Parabrachial Nucleus; Neurons; Axons
PubMed: 36317965
DOI: 10.7554/eLife.81868 -
Neuron May 2019SIM1-expressing paraventricular hypothalamus (PVH) neurons are key regulators of energy balance. Within the PVH population, melanocortin-4 receptor-expressing (PVH)...
SIM1-expressing paraventricular hypothalamus (PVH) neurons are key regulators of energy balance. Within the PVH population, melanocortin-4 receptor-expressing (PVH) neurons are known to regulate satiety and bodyweight, yet they account for only half of PVH neuron-mediated regulation. Here we report that PVH prodynorphin-expressing (PVH) neurons, which notably lack MC4Rs, function independently and additively with PVH neurons to account for the totality of PVH neuron-mediated satiety. Moreover, PVH neurons are necessary for prevention of obesity in an independent but equipotent manner to PVH neurons. While PVH and PVH neurons both project to the parabrachial complex (PB), they synaptically engage distinct efferent nodes, the pre-locus coeruleus (pLC), and central lateral parabrachial nucleus (cLPBN), respectively. PB-projecting PVH neurons, like PVH neurons, receive input from interoceptive ARC neurons, respond to caloric state, and are sufficient and necessary to control food intake. This expands the CNS satiety circuitry to include two non-overlapping PVH to hindbrain circuits.
Topics: Agouti-Related Protein; Animals; Arcuate Nucleus of Hypothalamus; Basic Helix-Loop-Helix Transcription Factors; Energy Metabolism; Enkephalins; Feeding Behavior; Locus Coeruleus; Mice; Neurons; Obesity; Parabrachial Nucleus; Paraventricular Hypothalamic Nucleus; Protein Precursors; Receptor, Melanocortin, Type 4; Repressor Proteins; Satiety Response
PubMed: 30879785
DOI: 10.1016/j.neuron.2019.02.028 -
Ugeskrift For Laeger Jan 2023Sudden pain of the eye, nose or face can be a symptom of stroke located to the pons. This case report is about a 73-year-old women with acute debut of right-sided...
Sudden pain of the eye, nose or face can be a symptom of stroke located to the pons. This case report is about a 73-year-old women with acute debut of right-sided hemiparesis, ataxia, gait disturbance, dysarthria, hemisensory defects and contralateral burning eye pain. MRI showed acute ischaemia of the left pons. The case adds to the growing literature of this rare presentation of posterior circulation stroke.
Topics: Humans; Female; Aged; Eye Pain; Pons; Stroke; Brain Stem Infarctions; Magnetic Resonance Imaging
PubMed: 36760190
DOI: No ID Found -
NeuroImage Dec 2022The cerebellum's involvement in cognitive, affective and motor functions is mediated by connections to different regions of the cerebral cortex. A distinctive feature of...
The cerebellum's involvement in cognitive, affective and motor functions is mediated by connections to different regions of the cerebral cortex. A distinctive feature of cortico-cerebellar loops that has been demonstrated in the animal work is a topographic organization that is preserved across its corticopontine, pontocerebellar, and cerebello-thalmo-cortical segments. Here we used tractography derived from diffusion imaging data to characterize the connections between the pons and the individual lobules of the cerebellum and generate a parcellation of the pons and middle cerebellar peduncle based on the pattern of connectivity. We identified a rostral to caudal gradient in the pons, similar to that observed in the animal work, such that rostral regions were preferentially connected to cerebellar lobules involved in non-motor, and caudal regions with motor regions. These findings advance our fundamental understanding of the cerebellum, and the parcellations we generated provide context for future research into the pontocerebellar tract's involvement in health and disease.
Topics: Animals; Pons; Cerebellum; Diffusion Magnetic Resonance Imaging; Cerebral Cortex; Neural Pathways; Brain Mapping; Magnetic Resonance Imaging
PubMed: 36252913
DOI: 10.1016/j.neuroimage.2022.119684 -
Cell Reports Apr 2024Pain that persists beyond the time required for tissue healing and pain that arises in the absence of tissue injury, collectively referred to as nociplastic pain, are...
Pain that persists beyond the time required for tissue healing and pain that arises in the absence of tissue injury, collectively referred to as nociplastic pain, are poorly understood phenomena mediated by plasticity within the central nervous system. The parabrachial nucleus (PBN) is a hub that relays aversive sensory information and appears to play a role in nociplasticity. Here, by preventing PBN Calca neurons from releasing neurotransmitters, we demonstrate that activation of Calca neurons is necessary for the manifestation and maintenance of chronic pain. Additionally, by directly stimulating Calca neurons, we demonstrate that Calca neuron activity is sufficient to drive nociplasticity. Aversive stimuli of multiple sensory modalities, such as exposure to nitroglycerin, cisplatin, or lithium chloride, can drive nociplasticity in a Calca-neuron-dependent manner. Aversive events drive nociplasticity in Calca neurons in the form of increased activity and excitability; however, neuroplasticity also appears to occur in downstream circuitry.
Topics: Animals; Parabrachial Nucleus; Neurons; Mice; Neuronal Plasticity; Male; Mice, Inbred C57BL
PubMed: 38583149
DOI: 10.1016/j.celrep.2024.114057 -
Proceedings of the National Academy of... Aug 2023The locus coeruleus (LC) is a small nucleus in the pons from which ascending and descending projections innervate major parts of the central nervous system. Its major...
The locus coeruleus (LC) is a small nucleus in the pons from which ascending and descending projections innervate major parts of the central nervous system. Its major transmitter is norepinephrine (NE). This system is evolutionarily conserved, including in humans, and its functions are associated with wakefulness and related to disorders, such as depression. Here, we performed single-cell ribonucleic acid-sequencing (RNA-seq) to subdivide neurons in the LC (24 clusters in total) into 3 NE, 17 glutamate, and 5 γ-aminobutyric acid (GABA) subtypes, and to chart their neuropeptide, cotransmitter, and receptor profiles. We found that NE neurons expressed at least 19 neuropeptide transcripts, notably galanin () but not , and >30 neuropeptide receptors. Among the galanin receptors, was expressed in ~19% of NE neurons, as was also confirmed by in situ hybridization. Unexpectedly, was highly expressed in GABA neurons surrounding the NE ensemble. Patch-clamp electrophysiology and cell-type-specific Ca-imaging using GCaMP6s revealed that a GalR1 agonist inhibits up to ~35% of NE neurons. This effect is direct and does not rely on feed-forward GABA inhibition. Our results define a role for the galanin system in NE functions, and a conceptual framework for the action of many other peptides and their receptors.
Topics: Humans; Animals; Mice; Galanin; Locus Coeruleus; Neurons; Peptide Hormones; Glutamic Acid; Norepinephrine
PubMed: 37487094
DOI: 10.1073/pnas.2222095120 -
Neuroscience and Biobehavioral Reviews Nov 2020Several lines of evidence have suggested for decades a role for norepinephrine (NE) in the pathophysiology and treatment of schizophrenia. Recent experimental findings... (Review)
Review
Several lines of evidence have suggested for decades a role for norepinephrine (NE) in the pathophysiology and treatment of schizophrenia. Recent experimental findings reveal anatomical and physiological properties of the locus coeruleus-norepinephrine (LC-NE) system and its involvement in brain function and cognition. Here, we integrate these two lines of evidence. First, we review the functional and structural properties of the LC-NE system and its impact on functional brain networks, cognition, and stress, with special emphasis on recent experimental and theoretical advances. Subsequently, we present an update about the role of LC-associated functions for the pathophysiology of schizophrenia, focusing on the cognitive and motivational deficits. We propose that schizophrenia phenomenology, in particular cognitive symptoms, may be explained by an abnormal interaction between genetic susceptibility and stress-initiated LC-NE dysfunction. This in turn, leads to imbalance between LC activity modes, dysfunctional regulation of brain network integration and neural gain, and deficits in cognitive functions. Finally, we suggest how recent development of experimental approaches can be used to characterize LC function in schizophrenia.
Topics: Brain; Humans; Locus Coeruleus; Neurons; Norepinephrine; Schizophrenia
PubMed: 32768486
DOI: 10.1016/j.neubiorev.2020.07.038