scholarly journals A labeled-line for cold from the periphery to the parabrachial nucleus

2019 ◽  
Author(s):  
Junichi Hachisuka ◽  
H. Richard Koerber ◽  
Sarah E. Ross
Keyword(s):  
Afferent Input ◽  
Parabrachial Nucleus ◽  
Projection Neurons ◽  
Inhibitory Interneurons ◽  
Major Pathway ◽  
Physiological Properties ◽  
Neural Substrate ◽  
Spinal Projection ◽  
Soma Size ◽  
The Brain

ABSTRACTSpinal projection neurons are a major pathway through which somatic stimuli are conveyed to the brain. However, the manner in which this information is coded is poorly understood. Here, we report the identification of a modality-selective spinoparabrachial (SPB) neuron subtype with unique properties. Specifically, we find that cold-selective SPB neurons are differentiated by selective afferent input, reduced neuropeptide sensitivity, distinct physiological properties, small soma size, and low basal drive. In addition, optogenetic experiments reveal that cold-selective SPB neurons are distinctive with respect to their connectivity, with little to no input from either Pdyn or Nos1 inhibitory interneurons. Together, these data define a neural substrate supporting a labeled-line for cold from the periphery to the brain.

THE AFFERENT PATH OF THE MILK-EJECTION REFLEX IN THE BRAIN OF THE RABBIT

1969 ◽  
Vol 43 (4) ◽  
pp. 663-671 ◽  
Author(s):  
J. S. TINDAL ◽  
G. S. KNAGGS ◽  
A. TURVEY
Keyword(s):  
Medial Geniculate Body ◽  
Milk Ejection ◽  
Major Pathway ◽  
Arterial Blood ◽  
Neural Substrate ◽  
Indifferent Electrode ◽  
Medial Geniculate ◽  
Milk Ejection Reflex ◽  
The Brain ◽  
Stimulation Technique

SUMMARY The afferent path of the milk-ejection reflex has been studied in the brain of the anaesthetized lactating rabbit. Electrical stimulation was applied between a monopolar electrode in the brain and an indifferent electrode in the scalp. The brain was transected at the mid-cerebellar level to eliminate sympathetico-adrenal activation, and intramammary pressure and arterial blood pressure were monitored to detect release of neurohypophysial hormones. In the mid-brain, the afferent path of the reflex is compact, lying in the lateral tegmentum of each side and passing forwards to lie medio-ventral to the medial geniculate body. On entering the diencephalon, the pathway on each side bifurcates: a dorsal path passing forwards in association with the extreme rostral central grey and periventricular region, and a ventral path ascending through the subthalamus. The dorsal and ventral paths reunite in the posterior hypothalamus. Delineating the pathway further forward in the hypothalamus, using a simple stimulation technique, was not possible because at this level it intermingles with efferent fibres descending from the paraventricular nucleus to the pituitary stalk. The afferent path of the reflex is concerned with the preferential release of oxytocin from the neurohypophysis, is not a major pathway for the release of vasopressin and its neural substrate in the mid-brain is believed to be the spinothalamic system of fibres.

scholarly journals A spinoparabrachial circuit defined by Tacr1 expression drives pain

2020 ◽  
Author(s):  
Arnab Barik ◽  
Anupama Sathyamurthy ◽  
James Thompson ◽  
Mathew Seltzer ◽  
Ariel Levine ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Negative Emotions ◽  
Parabrachial Nucleus ◽  
Projection Neurons ◽  
Coping Behaviors ◽  
Lateral Parabrachial Nucleus ◽  
Spinal Projection ◽  
Ongoing Pain ◽  
And Behaviors ◽  
Noxious Stimuli

AbstractPainful stimuli evoke a mixture of sensations, negative emotions and behaviors. These myriad effects are thought to be produced by parallel ascending circuits working in combination. Here we describe a pathway from spinal cord to brain for ongoing pain. Activation of a defined subset of spinal projection neurons expressing Tacr1 evokes a full repertoire of somatotopically-directed coping behaviors in the absence of noxious input. These cells project to a tiny cluster of Tacr1-positive neurons in the superior lateral parabrachial nucleus (PBN-SL) that themselves are responsive to sustained but not acute noxious stimuli. Activation of these PBN-SLTacr1 neurons alone does not trigger pain responses but instead serves to dramatically heighten nocifensive behaviors and suppress itch. Remarkably, mice with silenced PBN-SLTacr1 neurons ignore long-lasting noxious stimuli. These data reveal a spinoparabrachial pathway that plays a key role in the sensation of ongoing pain.

scholarly journals Robo2 Receptor Gates the Anatomical Divergence of Neurons Derived From a Common Precursor Origin

2021 ◽  
Vol 9 ◽  
Author(s):  
Maud Wurmser ◽  
Mridula Muppavarapu ◽  
Christine Mary Tait ◽  
Christophe Laumonnerie ◽  
Luz María González-Castrillón ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Development ◽  
Spatial Organization ◽  
Sensory Information ◽  
Receptor Expression ◽  
Projection Neurons ◽  
Mantle Zone ◽  
Common Precursor ◽  
Spinal Projection ◽  
The Brain

Sensory information relayed to the brain is dependent on complex, yet precise spatial organization of neurons. This anatomical complexity is generated during development from a surprisingly small number of neural stem cell domains. This raises the question of how neurons derived from a common precursor domain respond uniquely to their environment to elaborate correct spatial organization and connectivity. We addressed this question by exploiting genetically labeled mouse embryonic dorsal interneuron 1 (dI1) neurons that are derived from a common precursor domain and give rise to spinal projection neurons with distinct organization of cell bodies with axons projecting either commissurally (dI1c) or ipsilaterally (dI1i). In this study, we examined how the guidance receptor, Robo2, which is a canonical Robo receptor, influenced dI1 guidance during embryonic development. Robo2 was enriched in embryonic dI1i neurons, and loss of Robo2 resulted in misguidance of dI1i axons, whereas dI1c axons remained unperturbed within the mantle zone and ventral commissure. Further, Robo2 profoundly influenced dI1 cell body migration, a feature that was partly dependent on Slit2 signaling. These data suggest that dI1 neurons are dependent on Robo2 for their organization. This work integrated with the field support of a model whereby canonical Robo2 vs. non-canonical Robo3 receptor expression facilitates projection neurons derived from a common precursor domain to read out the tissue environment uniquely giving rise to correct anatomical organization.

scholarly journals UBE4B, a microRNA-9 target gene, promotes autophagy-mediated Tau degradation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Manivannan Subramanian ◽  
Seung Jae Hyeon ◽  
Tanuza Das ◽  
Yoon Seok Suh ◽  
Yun Kyung Kim ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ubiquitin Ligase ◽  
Therapeutic Approach ◽  
Target Gene ◽  
Neuroblastoma Cells ◽  
E3 Ligase ◽  
Tau Hyperphosphorylation ◽  
Phosphorylated Tau ◽  
Major Pathway ◽  
The Brain

AbstractThe formation of hyperphosphorylated intracellular Tau tangles in the brain is a hallmark of Alzheimer’s disease (AD). Tau hyperphosphorylation destabilizes microtubules, promoting neurodegeneration in AD patients. To identify suppressors of tau-mediated AD, we perform a screen using a microRNA (miR) library in Drosophila and identify the miR-9 family as suppressors of human tau overexpression phenotypes. CG11070, a miR-9a target gene, and its mammalian orthologue UBE4B, an E3/E4 ubiquitin ligase, alleviate eye neurodegeneration, synaptic bouton defects, and crawling phenotypes in Drosophila human tau overexpression models. Total and phosphorylated Tau levels also decrease upon CG11070 or UBE4B overexpression. In mammalian neuroblastoma cells, overexpression of UBE4B and STUB1, which encodes the E3 ligase CHIP, increases the ubiquitination and degradation of Tau. In the Tau-BiFC mouse model, UBE4B and STUB1 overexpression also increase oligomeric Tau degradation. Inhibitor assays of the autophagy and proteasome systems reveal that the autophagy-lysosome system is the major pathway for Tau degradation in this context. These results demonstrate that UBE4B, a miR-9 target gene, promotes autophagy-mediated Tau degradation together with STUB1, and is thus an innovative therapeutic approach for AD.

scholarly journals Human Monocytes Plasticity in Neurodegeneration

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 717
Author(s):  
Ilenia Savinetti ◽  
Angela Papagna ◽  
Maria Foti
Keyword(s):  
Neurodegenerative Disorders ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Surface Marker ◽  
First Line ◽  
Surface Marker Expression ◽  
Physiological Properties ◽  
Attractive Therapeutic Target ◽  
The Brain ◽  
Lateral Sclerosis

Monocytes play a crucial role in immunity and tissue homeostasis. They constitute the first line of defense during the inflammatory process, playing a role in the pathogenesis and progression of diseases, making them an attractive therapeutic target. They are heterogeneous in morphology and surface marker expression, which suggest different molecular and physiological properties. Recent evidences have demonstrated their ability to enter the brain, and, as a consequence, their hypothetical role in different neurodegenerative diseases. In this review, we will discuss the current knowledge about the correlation between monocyte dysregulation in the brain and/or in the periphery and neurological diseases in humans. Here we will focus on the most common neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis.

Effect of Subarachnoid Bupivacaine Block on Anesthetic Requirements for Thiopental in Rats 

1998 ◽  
Vol 88 (4) ◽  
pp. 1036-1042 ◽  
Author(s):  
Sunil Eappen ◽  
Igor Kissin
Keyword(s):  
Local Anesthetic ◽  
Direct Action ◽  
Afferent Input ◽  
Crossover Design ◽  
Hemodynamic Parameters ◽  
Motor Responses ◽  
Withdrawal Reflex ◽  
Corneal Reflex ◽  
To Receive ◽  
The Brain

Background Subarachnoid bupivacaine blockade has been reported to reduce thiopental and midazolam hypnotic requirements in patients. The purpose of this study was to examine if local anesthetically induced lumbar intrathecal blockade would reduce thiopental requirements for blockade of motor responses to noxious and nonnoxious stimuli in rats. Methods After intrathecal and external jugular catheter placement, rats were assigned randomly to two groups in a crossover design study, with each rat to receive either 10 microl of 0.75% bupivacaine or 10 microl of normal saline intrathecally. The doses of intravenously administered thiopental required to ablate the eyelid reflex, to block the withdrawal reflex of a front limb digit, and to block the corneal reflex were compared. In two separate groups of animals, hemodynamic parameters and concentrations of thiopental in the brain were compared between intrathecally administered bupivacaine and saline. Results The thiopental dose required to block the described responses was decreased with intrathecally administered bupivacaine versus intrathecally administered saline from (mean +/- SD) 40 +/- 5 to 24 +/- 4 mg/kg (P < 0.001) for the eyelid reflex, from 51 +/- 6 to 29 +/- 6 mg/kg (P < 0.005) for front limb withdrawal, and from 67 +/- 8 to 46 +/- 8 mg/kg (P < 0.01) for the corneal reflex. The concentration of thiopental in the brain at the time of corneal reflex blockade for the group given bupivacaine was significantly lower than in the group given saline (24.1 vs. 35.8 microg/g, P = 0.02). Conclusion This study demonstrates that lumbar intrathecally administered local anesthetic blockade decreases anesthetic requirements for thiopental for a spectrum of end points tested. This effect is due neither to altered pharmacokinetics nor to a direct action of the local anesthetic on the brain; rather, it is most likely due to decreased afferent input.

Еnactivist Criticism of the Neurobiological Theory of Consciousness

2021 ◽  
pp. 76-80
Author(s):  
Anastasia O. Shabalina ◽  
Keyword(s):  
Philosophy Of Mind ◽  
Point Of View ◽  
Science Methods ◽  
Neural Processes ◽  
Neural Substrate ◽  
Critical Revision ◽  
Concept Of Information ◽  
The Mind ◽  
The Brain ◽  
Person Experience

The article considers the main arguments against the neurobiological theory of consciousness from the point of view of the enactivist approach within the philosophy of mind. The neurobiological theory of consciousness, which reduces consciousness to neural activity, is currently the dominant approach to the mind-body problem. The neurobiological theory emerged as a result of advances in research on the phenomena of consciousness and through the development of technologies for visualizing the internal processes of mind. However, at the very heart of this theory, there is a number of logical contradictions. The non-reductive enactivist approach to consciousness, introduced in this article, contributes to the existing argumentation against the reduction of consciousness to neural processes with remonstrations that take into account the modern neuroscientific data. The article analyzes the argumentation of the sensorimotor enactivism developed by A. Noe and offers the account of the teleosemantic approach to the concept of information provided by R. Cao. The key problems of the neurobiological theory of consciousness are highlighted, and the objections emerging within the framework of the enactivist approach are analyzed. Since the main concepts on which the neural theory is based are the concepts of neural substrate, cognition as representation, and information as a unit of cognition, the author of the article presents three key enactivist ideas that oppose them. First, the enactivist concept of cognition as action allows us to consider the first-person experience as a mode of action, and not as a state of the brain substrate. Second, the article deals with the “explanatory externalism” argument proposed by Noe, who refutes the image of cognition as a representation in the brain. Finally, in order to critically revise the concept of information as a unit of cognition, the author analyzes Cao’s idea, which represents a teleosemantic approach, but is in line with the general enactivist argumentation. Cao shows that the application of the concept “information” to neural processes is problematic: no naturalized information is found in the brain as a physical substrate. A critical revision of beliefs associated with the neural theory of consciousness leads us to recognize that there are not enough grounds for reducing consciousness to processes that take place in the brain. That is why Noe calls expectations that the visualization of processes taking place in the brain with the help of the modern equipment will be able to depict the experience of consciousness the “new phrenology”, thus indicating the naive character of neural reduction. The article concludes that natural science methods are insufficient for the study of consciousness.

Differential Involvement of Projection Neurons During Emergence of Spontaneous Activity in the Developing Avian Hindbrain

2009 ◽  
Vol 101 (2) ◽  
pp. 591-602 ◽  
Author(s):  
Hiraku Mochida ◽  
Gilles Fortin ◽  
Jean Champagnat ◽  
Joel C. Glover
Keyword(s):  
Spontaneous Activity ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Charge Coupled Device ◽  
Neuron Populations ◽  
Motor Nerves ◽  
Differential Involvement ◽  
A Charge ◽  
The Brain ◽  
Calcium Green

To better characterize the emergence of spontaneous neuronal activity in the developing hindbrain, spontaneous activity was recorded optically from defined projection neuron populations in isolated preparations of the brain stem of the chicken embryo. Ipsilaterally projecting reticulospinal (RS) neurons and several groups of vestibuloocular (VO) neurons were labeled retrogradely with Calcium Green-1 dextran amine and spontaneous calcium transients were recorded using a charge-coupled-device camera mounted on a fluorescence microscope. Simultaneous extracellular recordings were made from one of the trigeminal motor nerves (nV) to register the occurrence of spontaneous synchronous bursts of activity. Two types of spontaneous activity were observed: synchronous events (SEs), which occurred in register with spontaneous bursts in nV once every few minutes and were tetrodotoxin (TTX) dependent, and asynchronous events (AEs), which occurred in the intervals between SEs and were TTX resistant. AEs occurred developmentally before SEs and were in general smaller and more variable in amplitude than SEs. SEs appeared at the same stage as nV bursts early on embryonic day 4, first in RS neurons and then in VO neurons. All RS neurons participated equally in SEs from the outset, whereas different subpopulations of VO neurons participated differentially, both in terms of the proportion of neurons that exhibited SEs, the fidelity with which the SEs in individual neurons followed the nV bursts, and the developmental stage at which SEs appeared and matured. The results show that spontaneous activity is expressed heterogeneously among hindbrain projection neuron populations, suggesting its differential involvement in the formation of different functional neuronal circuits.

scholarly journals Divergent neural pathways emanating from the lateral parabrachial nucleus mediate distinct components of the pain response

2019 ◽  
Author(s):  
Michael C. Chiang ◽  
Eileen K. Nguyen ◽  
Andrew E. Papale ◽  
Sarah E. Ross
Keyword(s):  
Ventromedial Hypothalamus ◽  
Parabrachial Nucleus ◽  
Projection Neurons ◽  
Pain Response ◽  
Neural Pathways ◽  
Bed Nucleus ◽  
Lateral Parabrachial Nucleus ◽  
Efferent Projections ◽  
Efferent Neurons ◽  
Nociceptive Input

ABSTRACTThe lateral parabrachial nucleus (lPBN) is a major target of spinal projection neurons conveying nociceptive input into supraspinal structures. However, the functional role of distinct lPBN efferents for diverse nocifensive responses have remained largely uncharacterized. Here, we show that two populations of efferent neurons from different regions of the lPBN collateralize to distinct targets. Activation of efferent projections to the ventromedial hypothalamus (VMH) or lateral periaqueductal gray (lPAG) drive escape behaviors, whereas the activation of lPBN efferents to the bed nucleus stria terminalis (BNST) or central amygdala (CEA) generates an aversive memory. Finally, we provide evidence that dynorphin expressing neurons span cytoarchitecturally distinct domains of the lPBN to coordinate these distinct aspects of the nocifensive response.HIGHLIGHTSSpatially segregated neurons in the lPBN collateralize to distinct targets.Distinct output pathways give rise to separate aspects of the pain response.Dynorphin neurons within the lPBN convey noxious information across subdivisions.eTOC BLURBChiang et al. reveal that neurons in spatially segregated regions of the lateral parabrachial nucleus collateralize to distinct targets, and that activation of distinct efferents gives rise to separate components of the nocifensive response.

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