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Cell Oct 2018The gut is now recognized as a major regulator of motivational and emotional states. However, the relevant gut-brain neuronal circuitry remains unknown. We show that...
The gut is now recognized as a major regulator of motivational and emotional states. However, the relevant gut-brain neuronal circuitry remains unknown. We show that optical activation of gut-innervating vagal sensory neurons recapitulates theĀ hallmark effects of stimulating brain reward neurons. Specifically, right, but not left, vagal sensory ganglion activation sustained self-stimulation behavior, conditioned both flavor and place preferences, and induced dopamine release from Substantia nigra. Cell-specific transneuronal tracing revealed asymmetric ascending pathways of vagal origin throughout the CNS. In particular, transneuronal labeling identified the glutamatergic neurons of the dorsolateral parabrachial region as the obligatory relay linking the right vagal sensory ganglion to dopamine cells in Substantia nigra. Consistently, optical activation of parabrachio-nigral projections replicated the rewarding effects of right vagus excitation. Our findings establish the vagal gut-to-brain axis as an integral component of the neuronal reward pathway. They also suggest novel vagal stimulation approaches to affective disorders.
Topics: Afferent Pathways; Animals; Dopamine; Dopaminergic Neurons; Glutamic Acid; Intestines; Male; Mice; Mice, Inbred C57BL; Optogenetics; Reward; Substantia Nigra; Vagus Nerve
PubMed: 30245012
DOI: 10.1016/j.cell.2018.08.049 -
Handbook of Clinical Neurology 2019The gustatory system contributes to the flavor of foods and beverages and communicates information about nutrients and poisons. This system has evolved to detect and... (Review)
Review
The gustatory system contributes to the flavor of foods and beverages and communicates information about nutrients and poisons. This system has evolved to detect and ultimately respond to hydrophilic molecules dissolved in saliva. Taste receptor cells, located in taste buds and distributed throughout the oral cavity, activate nerve afferents that project to the brainstem. From here, information propagates to thalamic, subcortical, and cortical areas, where it is integrated with information from other sensory systems and with homeostatic, visceral, and affective processes. There is considerable divergence, as well as convergence, of information between multiple regions of the central nervous system that interact with the taste pathways, with reciprocal connections occurring between the involved regions. These widespread interactions among multiple systems are crucial for the perception of food. For example, memory, hunger, satiety, and visceral changes can directly affect and can be affected by the experience of tasting. In this chapter, we review the literature on the central processing of taste with a specific focus on the anatomic and physiologic responses of single neurons. Emphasis is placed on how information is distributed along multiple systems with the goal of better understanding how the rich and complex sensations associated with flavor emerge from large-scale, systems-wide, interactions.
Topics: Afferent Pathways; Animals; Brain; Humans; Nerve Net; Neurons; Taste; Thalamus
PubMed: 31604547
DOI: 10.1016/B978-0-444-63855-7.00012-5 -
European Journal of Pain (London,... Aug 2005The perception of pain due to an acute injury or in clinical pain states undergoes substantial processing at supraspinal levels. Supraspinal, brain mechanisms are... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
The perception of pain due to an acute injury or in clinical pain states undergoes substantial processing at supraspinal levels. Supraspinal, brain mechanisms are increasingly recognized as playing a major role in the representation and modulation of pain experience. These neural mechanisms may then contribute to interindividual variations and disabilities associated with chronic pain conditions.
OBJECTIVE
To systematically review the literature regarding how activity in diverse brain regions creates and modulates the experience of acute and chronic pain states, emphasizing the contribution of various imaging techniques to emerging concepts.
DATA SOURCES
MEDLINE and PRE-MEDLINE searches were performed to identify all English-language articles that examine human brain activity during pain, using hemodynamic (PET, fMRI), neuroelectrical (EEG, MEG) and neurochemical methods (MRS, receptor binding and neurotransmitter modulation), from January 1, 1988 to March 1, 2003. Additional studies were identified through bibliographies.
STUDY SELECTION
Studies were selected based on consensus across all four authors. The criteria included well-designed experimental procedures, as well as landmark studies that have significantly advanced the field.
DATA SYNTHESIS
Sixty-eight hemodynamic studies of experimental pain in normal subjects, 30 in clinical pain conditions, and 30 using neuroelectrical methods met selection criteria and were used in a meta-analysis. Another 24 articles were identified where brain neurochemistry of pain was examined. Technical issues that may explain differences between studies across laboratories are expounded. The evidence for and the respective incidences of brain areas constituting the brain network for acute pain are presented. The main components of this network are: primary and secondary somatosensory, insular, anterior cingulate, and prefrontal cortices (S1, S2, IC, ACC, PFC) and thalamus (Th). Evidence for somatotopic organization, based on 10 studies, and psychological modulation, based on 20 studies, is discussed, as well as the temporal sequence of the afferent volley to the cortex, based on neuroelectrical studies. A meta-analysis highlights important methodological differences in identifying the brain network underlying acute pain perception. It also shows that the brain network for acute pain perception in normal subjects is at least partially distinct from that seen in chronic clinical pain conditions and that chronic pain engages brain regions critical for cognitive/emotional assessments, implying that this component of pain may be a distinctive feature between chronic and acute pain. The neurochemical studies highlight the role of opiate and catecholamine transmitters and receptors in pain states, and in the modulation of pain with environmental and genetic influences.
CONCLUSIONS
The nociceptive system is now recognized as a sensory system in its own right, from primary afferents to multiple brain areas. Pain experience is strongly modulated by interactions of ascending and descending pathways. Understanding these modulatory mechanisms in health and in disease is critical for developing fully effective therapies for the treatment of clinical pain conditions.
Topics: Afferent Pathways; Brain; Diagnostic Imaging; Humans; Nerve Net; Nociceptors; Pain; Pain, Intractable; Perception; Sensation
PubMed: 15979027
DOI: 10.1016/j.ejpain.2004.11.001 -
Cell Oct 2019The ability to sense sour provides an important sensory signal to prevent the ingestion of unripe, spoiled, or fermented foods. Taste and somatosensory receptors in the...
The ability to sense sour provides an important sensory signal to prevent the ingestion of unripe, spoiled, or fermented foods. Taste and somatosensory receptors in the oral cavity trigger aversive behaviors in response to acid stimuli. Here, we show that the ion channel Otopetrin-1, a proton-selective channel normally involved in the sensation of gravity in the vestibular system, is essential for sour sensing in the taste system. We demonstrate that knockout of Otop1 eliminates acid responses from sour-sensing taste receptor cells (TRCs). In addition, we show that mice engineered to express otopetrin-1 in sweet TRCs have sweet cells that also respond to sour stimuli. Next, we genetically identified the taste ganglion neurons mediating each of the five basic taste qualities and demonstrate that sour taste uses its own dedicated labeled line from TRCs in the tongue to finely tuned taste neurons in the brain to trigger aversive behaviors.
Topics: Acids; Afferent Pathways; Animals; Brain; Female; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Taste; Taste Buds; Taste Perception
PubMed: 31543264
DOI: 10.1016/j.cell.2019.08.031 -
Nature Reviews. Neuroscience Dec 2010Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The... (Review)
Review
Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region.
Topics: Afferent Pathways; Animals; Brain; Disease Models, Animal; Humans; Nerve Net; Nociceptors; Pain; Posterior Horn Cells
PubMed: 21068766
DOI: 10.1038/nrn2947 -
Neuron Sep 2020The parabrachial nucleus (PBN) is one of the major targets of spinal projection neurons and plays important roles in pain. However, the architecture of the...
The parabrachial nucleus (PBN) is one of the major targets of spinal projection neurons and plays important roles in pain. However, the architecture of the spinoparabrachial pathway underlying its functional role in nociceptive information processing remains elusive. Here, we report that the PBN directly relays nociceptive signals from the spinal cord to the intralaminar thalamic nuclei (ILN). We demonstrate that the spinal cord connects with the PBN in a bilateral manner and that the ipsilateral spinoparabrachial pathway is critical for nocifensive behavior. We identify Tacr1-expressing neurons as the major neuronal subtype in the PBN that receives direct spinal input and show that these neurons are critical for processing nociceptive information. Furthermore, PBN neurons receiving spinal input form functional monosynaptic excitatory connections with neurons in the ILN, but not the amygdala. Together, our results delineate the neural circuit underlying nocifensive behavior, providing crucial insight into the circuit mechanism underlying nociceptive information processing.
Topics: Afferent Pathways; Amygdala; Animals; Functional Laterality; Intralaminar Thalamic Nuclei; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Nociception; Parabrachial Nucleus; Spinal Cord
PubMed: 32649865
DOI: 10.1016/j.neuron.2020.06.017 -
Seminars in Nephrology Jan 2019Neuroimmune interaction is an emerging concept, wherein the nervous system modulates the immune system and vice versa. This concept is gaining attention as a novel... (Review)
Review
Neuroimmune interaction is an emerging concept, wherein the nervous system modulates the immune system and vice versa. This concept is gaining attention as a novel therapeutic target in various inflammatory diseases including acute kidney injury (AKI). Vagus nerve stimulation or treatment with pulsed ultrasound activates the cholinergic anti-inflammatory pathway to prevent AKI in mice. The kidneys are innervated by sympathetic efferent and sensory afferent neurons, and these neurons also may play a role in the modulation of inflammation in AKI. In this review, we discuss several neural circuits with respect to the control of renal inflammation and AKI as well as optogenetics as a novel tool for understanding these complex neural circuits.
Topics: Acetylcholine; Acute Kidney Injury; Afferent Pathways; Animals; Efferent Pathways; Humans; Inflammation; Kidney; Neuroimmunomodulation; Optogenetics; Sympathectomy; Sympathetic Nervous System; Vagus Nerve Stimulation
PubMed: 30606410
DOI: 10.1016/j.semnephrol.2018.10.008 -
The Journal of Urology Apr 2010Much current research on lower urinary tract physiology focuses on afferent mechanisms. The main goals are to define and control the signaling pathways by which afferent... (Review)
Review
PURPOSE
Much current research on lower urinary tract physiology focuses on afferent mechanisms. The main goals are to define and control the signaling pathways by which afferent information is generated and conveyed to the central nervous system. We summarize recent research on bladder afferent mechanisms.
MATERIALS AND METHODS
We systematically reviewed the literature by searching PubMed up to June 2009 with focus on the last 5 years.
RESULTS
At least 2 signaling pathways can be identified, including the urothelial and the myogenic pathway. The urothelial pathway is a functional unit consisting of the urothelium, interstitial cells and afferent nerves in the lamina propria. Signaling occurs via muscle-mucosal mechanoreceptors, mucosal mechanoreceptors and chemoreceptors. The myogenic pathway is activated via in-series mechanoreceptors responding to distention and via spontaneous contractile activity in units of myocytes generating afferent noise.
CONCLUSIONS
To control dysfunctional micturition we must know more about all components involved in normal micturition control, including how afferent information is handled by the central nervous system.
Topics: Afferent Pathways; Humans; Urinary Bladder
PubMed: 20171668
DOI: 10.1016/j.juro.2009.12.060 -
Journal of Diabetes Investigation Nov 2016The hypothalamus is a center of food intake and energy metabolism regulation. Information signals from peripheral organs are mediated through the circulation or the... (Review)
Review
The hypothalamus is a center of food intake and energy metabolism regulation. Information signals from peripheral organs are mediated through the circulation or the vagal afferent pathway and input into the hypothalamus, where signals are integrated to determine various behaviors, such as eating. Numerous appetite-regulating peptides are expressed in the central nervous system and the peripheral organs, and interact in a complex manner. Of such peptides, gut peptides are known to bind to receptors at the vagal afferent pathway terminal that extend into the mucosal layer of the digestive tract, modulate the electrical activity of the vagus nerve, and subsequently send signals to the solitary nucleus and furthermore to the hypothalamus. All peripheral peptides other than ghrelin suppress appetite, and they synergistically suppress appetite through the vagus nerve. In contrast, the appetite-enhancing peptide, ghrelin, antagonizes the actions of appetite-suppressing peptides through the vagus nerve, and appetite-suppressing peptides have attenuated effects in obesity as a result of inflammation in the vagus nerve. With greater understanding of the mechanism for food intake and energy metabolism regulation, medications that apply the effects of appetite-regulating peptides or implantable devices that electrically stimulate the vagus nerve are being investigated as novel treatments for obesity in basic and clinical studies.
Topics: Afferent Pathways; Animals; Appetite Regulation; Diabetes Mellitus; Gastrointestinal Tract; Humans; Hypothalamus; Neurons; Obesity; Peptides; Signal Transduction; Vagus Nerve
PubMed: 27180615
DOI: 10.1111/jdi.12492 -
Neurology(R) Neuroimmunology &... Mar 2020
Topics: Afferent Pathways; Gray Matter; Humans; Optic Neuritis; Visual Pathways
PubMed: 32229640
DOI: 10.1212/NXI.0000000000000667