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Veterinary Journal (London, England :... Jul 2018The mechanisms by which noxious stimuli produce the sensation of pain in animals are complex. Noxious stimuli are transduced at the periphery and transmitted to the CNS,... (Review)
Review
The mechanisms by which noxious stimuli produce the sensation of pain in animals are complex. Noxious stimuli are transduced at the periphery and transmitted to the CNS, where this information is subject to considerable modulation. Finally, the information is projected to the brain where it is perceived as pain. Additionally, plasticity can develop in the pain pathway and hyperalgesia and allodynia may develop through sensitisation both peripherally and centrally. A large number of different ion channels, receptors, and cell types are involved in pain perception, and it is hoped that through a better understanding of these, new and refined treatments for pain will result.
Topics: Acute Pain; Animals; Hyperalgesia; Neural Pathways; Nociceptors; Pain Measurement; Sensation; Signal Transduction; Spinal Cord
PubMed: 30089546
DOI: 10.1016/j.tvjl.2018.05.004 -
Molecular Neurobiology Feb 2019The prefrontal cortex (PFC) is not only important in executive functions, but also pain processing. The latter is dependent on its connections to other areas of the... (Review)
Review
The prefrontal cortex (PFC) is not only important in executive functions, but also pain processing. The latter is dependent on its connections to other areas of the cerebral neocortex, hippocampus, periaqueductal gray (PAG), thalamus, amygdala, and basal nuclei. Changes in neurotransmitters, gene expression, glial cells, and neuroinflammation occur in the PFC during acute and chronic pain, that result in alterations to its structure, activity, and connectivity. The medial PFC (mPFC) could serve dual, opposing roles in pain: (1) it mediates antinociceptive effects, due to its connections with other cortical areas, and as the main source of cortical afferents to the PAG for modulation of pain. This is a 'loop' where, on one side, a sensory stimulus is transformed into a perceptual signal through high brain processing activity, and perceptual activity is then utilized to control the flow of afferent sensory stimuli at their entrance (dorsal horn) to the CNS. (2) It could induce pain chronification via its corticostriatal projection, possibly depending on the level of dopamine receptor activation (or lack of) in the ventral tegmental area-nucleus accumbens reward pathway. The PFC is involved in biopsychosocial pain management. This includes repetitive transcranial magnetic stimulation, transcranial direct current stimulation, antidepressants, acupuncture, cognitive behavioral therapy, mindfulness, music, exercise, partner support, empathy, meditation, and prayer. Studies demonstrate the role of the PFC during placebo analgesia, and in establishing links between pain and depression, anxiety, and loss of cognition. In particular, losses in PFC grey matter are often reversible after successful treatment of chronic pain.
Topics: Animals; Dopamine; Humans; Neural Pathways; Pain; Pain Perception; Prefrontal Cortex
PubMed: 29876878
DOI: 10.1007/s12035-018-1130-9 -
Current Biology : CB Oct 2020A fundamental question of physiology is how gut-brain signaling stimulates appetite. While many studies have emphasized the importance of vagal afferents to the brain in...
A fundamental question of physiology is how gut-brain signaling stimulates appetite. While many studies have emphasized the importance of vagal afferents to the brain in inducing satiation, little is known about whether and how the vagal-mediated gut-brain pathway senses orexigenic signals and stimulates feeding. Here, we identified a previously uncharacterized population of fasting-activated catecholaminergic neurons in the nucleus of the solitary tract (NTS). After characterizing the anatomical complexity among NTS catecholaminergic neurons, we surprisingly found that activation of NTS epinephrine (E) neurons co-expressing neuropeptide Y (NPY) stimulated feeding, whereas activation of NTS norepinephrine (NE) neurons suppressed feeding. Monosynaptic tracing/activation experiments then showed that these NTS neurons receive direct vagal afferents from nodose neurons. Moreover, activation of the vagal→NPY/E neural circuit stimulated feeding. Our study reveals an orexigenic role of the vagal→NTS pathway in controlling feeding, thereby providing important insights about how gut-brain signaling regulates feeding behavior.
Topics: Animals; Appetite; Eating; Epinephrine; Hunger; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neural Pathways; Neurons, Afferent; Neuropeptide Y; Norepinephrine; Solitary Nucleus; Vagus Nerve
PubMed: 32822608
DOI: 10.1016/j.cub.2020.07.084 -
Nature Reviews. Neuroscience Sep 2013Mood disorders are common and debilitating conditions characterized in part by profound deficits in reward-related behavioural domains. A recent literature has... (Review)
Review
Mood disorders are common and debilitating conditions characterized in part by profound deficits in reward-related behavioural domains. A recent literature has identified important structural and functional alterations within the brain's reward circuitry--particularly in the ventral tegmental area-nucleus accumbens pathway--that are associated with symptoms such as anhedonia and aberrant reward-associated perception and memory. This Review synthesizes recent data from human and rodent studies from which emerges a circuit-level framework for understanding reward deficits in depression. We also discuss some of the molecular and cellular underpinnings of this framework, ranging from adaptations in glutamatergic synapses and neurotrophic factors to transcriptional and epigenetic mechanisms.
Topics: Animals; Brain; Humans; Mood Disorders; Neural Pathways; Reward
PubMed: 23942470
DOI: 10.1038/nrn3381 -
The Journal of Clinical Investigation Dec 2020The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the...
The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we show that lesions in the dmPFC induced an algesic and anxious state. Using multiple tracing methods including a rabies-based transsynaptic tracing method, we outlined an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG). Specific activation of the dmPFC/vlPAG neural pathway by optogenetic manipulation produced analgesic and antianxiety effects in a mouse model of chronic pain. Inhibitory neurons in the dmPFC were specifically activated using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of the GABAA receptor (GABAAR) or mGluR1 were applied to the dmPFC, which produced analgesic and antianxiety effects. In summary, the results of our study suggest that the dmPFC/vlPAG neural pathway might participate in the maintenance of pain thresholds and antianxiety behaviors under normal conditions, while silencing or suppressing the dmPFC/vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.
Topics: Animals; Anti-Anxiety Agents; Chronic Pain; Mice; Mice, Transgenic; Neural Pathways; Optogenetics; Prefrontal Cortex; Receptors, Metabotropic Glutamate
PubMed: 32841213
DOI: 10.1172/JCI127607 -
Seminars in Pediatric Neurology Apr 2018Movement disorders typically arise from dysfunction of the basal ganglia (BG), cerebellum, or both. The BG-a group of deep, subcortical structures-form complex circuits... (Review)
Review
Movement disorders typically arise from dysfunction of the basal ganglia (BG), cerebellum, or both. The BG-a group of deep, subcortical structures-form complex circuits that shape motor control and motor learning, as well as limbic and associative functions. In this article, we summarize the anatomy and physiology of the BG and cerebellum, and briefly highlight the clinical syndromes that may arise in the context of their injury or dysfunction.
Topics: Animals; Basal Ganglia; Humans; Movement Disorders; Neural Pathways; Syndrome
PubMed: 29735113
DOI: 10.1016/j.spen.2017.12.005 -
Nature Jul 2010Neural circuits of the basal ganglia are critical for motor planning and action selection. Two parallel basal ganglia pathways have been described, and have been...
Neural circuits of the basal ganglia are critical for motor planning and action selection. Two parallel basal ganglia pathways have been described, and have been proposed to exert opposing influences on motor function. According to this classical model, activation of the 'direct' pathway facilitates movement and activation of the 'indirect' pathway inhibits movement. However, more recent anatomical and functional evidence has called into question the validity of this hypothesis. Because this model has never been empirically tested, the specific function of these circuits in behaving animals remains unknown. Here we report direct activation of basal ganglia circuitry in vivo, using optogenetic control of direct- and indirect-pathway medium spiny projection neurons (MSNs), achieved through Cre-dependent viral expression of channelrhodopsin-2 in the striatum of bacterial artificial chromosome transgenic mice expressing Cre recombinase under control of regulatory elements for the dopamine D1 or D2 receptor. Bilateral excitation of indirect-pathway MSNs elicited a parkinsonian state, distinguished by increased freezing, bradykinesia and decreased locomotor initiations. In contrast, activation of direct-pathway MSNs reduced freezing and increased locomotion. In a mouse model of Parkinson's disease, direct-pathway activation completely rescued deficits in freezing, bradykinesia and locomotor initiation. Taken together, our findings establish a critical role for basal ganglia circuitry in the bidirectional regulation of motor behaviour and indicate that modulation of direct-pathway circuitry may represent an effective therapeutic strategy for ameliorating parkinsonian motor deficits.
Topics: Animals; Basal Ganglia; Channelrhodopsins; Chromosomes, Artificial, Bacterial; Disease Models, Animal; Gait; Hypokinesia; Integrases; Mice; Mice, Transgenic; Models, Neurological; Motor Activity; Neostriatum; Neural Pathways; Neurons; Oxidopamine; Parkinson Disease; Psychomotor Performance; Receptors, Dopamine
PubMed: 20613723
DOI: 10.1038/nature09159 -
Neuron Nov 2017Mapping neural circuits across defined synapses is essential for understanding brain function. Here we describe trans-Tango, a technique for anterograde transsynaptic...
Mapping neural circuits across defined synapses is essential for understanding brain function. Here we describe trans-Tango, a technique for anterograde transsynaptic circuit tracing and manipulation. At the core of trans-Tango is a synthetic signaling pathway that is introduced into all neurons in the animal. This pathway converts receptor activation at the cell surface into reporter expression through site-specific proteolysis. Specific labeling is achieved by presenting a tethered ligand at the synapses of genetically defined neurons, thereby activating the pathway in their postsynaptic partners and providing genetic access to these neurons. We first validated trans-Tango in the Drosophila olfactory system and then implemented it in the gustatory system, where projections beyond the first-order receptor neurons are not fully characterized. We identified putative second-order neurons within the sweet circuit that include projection neurons targeting known neuromodulation centers in the brain. These experiments establish trans-Tango as a flexible platform for transsynaptic circuit analysis.
Topics: Animals; Animals, Genetically Modified; Drosophila; Neural Pathways; Neuroanatomical Tract-Tracing Techniques; Neurons; Olfactory Pathways; Taste Perception
PubMed: 29107518
DOI: 10.1016/j.neuron.2017.10.011 -
Neuropsychology Review Jun 2010
Topics: Brain; Humans; Mental Disorders; Mental Processes; Neural Pathways; Neurons
PubMed: 20495960
DOI: 10.1007/s11065-010-9136-8 -
Frontiers in Neural Circuits 2022Itch-induced scratching is an evolutionarily conserved behavioral response that protects organisms from potential parasites/irritants in their immediate vicinity. How... (Review)
Review
Itch-induced scratching is an evolutionarily conserved behavioral response that protects organisms from potential parasites/irritants in their immediate vicinity. How the exposure to a pruritogen is translated to the perception of itch and how that perception drives scratching directed towards the site of exposure remains poorly understood. In this review, we focus on the recent findings that shed light on the neural pathways in the brain that underlie itch-induced scratching. We compare the molecularly defined itch pathways with the known pain circuits as they have anatomical and functional overlap. We review the roles played by the neurons in the spinoparabrachial pathway-comprising of the neurons in the spinal cord and the parabrachial nucleus (PBN), which acts as a hub for transmitting itch information across the brain. Lastly, we deliberate on scratching as a behavioral measure of the intensity of itch and its implication in unraveling the underlying supraspinal mechanisms. In summary, we provide a resource on the recent advances and discuss a path forward on our understanding of the neural circuits for itch.
Topics: Humans; Neural Pathways; Neurons; Parabrachial Nucleus; Pruritus; Spinal Cord
PubMed: 35250493
DOI: 10.3389/fncir.2022.805831