scholarly journals Presynaptic inhibition of cutaneous afferents prevents self-generated itch

2019 ◽  
Author(s):  
Augusto Escalante ◽  
Rüdiger Klein
Keyword(s):  
Wide Spectrum ◽  
Inhibitory Neurons ◽  
Cutaneous Afferents ◽  
List Type ◽  
Spinal Neurons ◽  
Skin Sensitivity ◽  
Gastrin Releasing Peptide ◽  
Hairy Skin ◽  
Chronic Itch ◽  
Excessive Grooming

SummaryChronic itch represents an incapacitating burden on patients suffering a wide spectrum of diseases. Despite recent advances in our understanding of the cells and circuits implicated in the processing of itch information, chronic itch often presents itself without apparent cause. Here, we identify a spinal subpopulation of inhibitory neurons defined by the expression of Ptf1a involved in gating mechanosensory information self-generated during movement. These neurons receive tactile and motor input and establish presynaptic inhibitory contacts on mechanosensory afferents. Loss of Ptf1a neurons leads to increased hairy skin sensitivity and chronic itch, at least partially mediated through the classic itch pathway involving gastrin releasing peptide receptor (GRPR) spinal neurons. Conversely, chemogenetic activation of GRPR neurons elicits itch which is suppressed by concomitant activation of Ptf1a neurons. These findings shed new light on the circuit mechanisms implicated in chronic itch and open novel targets for therapy developments.Highlights*Ptf1a specifies adult spinal presynaptic neurons contacting cutaneous afferents*Loss of spinal Ptf1a+ neurons leads to self-generated itch and excessive grooming*Absence of Ptf1a+ neurons increases hairy skin sensitivity which triggers scratching*GRPR+ neurons act downstream of Ptf1a+ neurons in spontaneous itch

scholarly journals Counter-stimuli Inhibit GRPR Neurons via GABAergic Signaling in the Spinal Cord

2018 ◽  
Author(s):  
Rita Bardoni ◽  
Devin M. Barry ◽  
Hui Li ◽  
Kai-Feng Shen ◽  
Joseph Jeffry ◽  
...  
Keyword(s):  
Neural Mechanisms ◽  
Projection Neurons ◽  
List Type ◽  
Inhibitory Effects ◽  
Spinal Neurons ◽  
Chronic Itch ◽  
Spinal Mechanism ◽  
Itch Sensation ◽  
Neurokinin 1

AbstractA myriad of counter-stimuli, including algogens and cooling, could inhibit itch sensation; however, the underlying molecular and neural mechanisms remain poorly understood. Here, we show that the spinal neurons expressing gastrin releasing peptide receptor (GRPR) primarily comprise excitatory interneurons that receive direct and indirect inputs from C and Aδ fibers and form contacts with projection neurons expressing the neurokinin 1 receptor (NK1R). Optical or chemogenetic activation of GRPR neurons evokes itch behavior that is partly dependent on NK1R activation. Importantly, we show that noxious or cooling counter-stimuli inhibit the activity of GRPR neurons via GABAergic signaling. By contrast, capsaicin, which could evoke a mix of itch and pain sensations, could exert both excitatory and inhibitory effects on GRPR neurons. These data strengthen the role of GRPR neurons as a key circuit for itch transmission and illustrate a spinal mechanism whereby counter-stimuli inhibit itch by suppressing the function of GRPR neurons.HighlightsActivation of GRPR neurons evokes itch and is dependent upon NK1R activationGRPR neurons receive both direct and indirect inputs from C/Aδ fibersCounter-stimuli inhibit GRPR neurons via GABAergic signalingIncreased excitability of GRPR neurons in chronic itch condition

scholarly journals Subanesthetic ketamine reactivates adult cortical plasticity to restore vision from amblyopia

2020 ◽  
Author(s):  
Steven F. Grieco ◽  
Xin Qiao ◽  
Xiaoting Zheng ◽  
Yongjun Liu ◽  
Lujia Chen ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Neural Plasticity ◽  
Cortical Plasticity ◽  
Brain Plasticity ◽  
Excitatory Input ◽  
Inhibitory Neurons ◽  
List Type ◽  
Visual Cortical

SummarySubanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine’s effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically induces down-regulation of neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons in mouse visual cortex. NRG1 downregulation in PV neurons co-tracks both the fast onset and sustained decreases in synaptic inhibition to excitatory neurons, along with reduced synaptic excitation to PV neurons in vitro and in vivo following a single ketamine treatment. These effects are blocked by exogenous NRG1 as well as PV targeted receptor knockout. Thus ketamine reactivation of adult visual cortical plasticity is mediated through rapid and sustained cortical disinhibition via downregulation of PV-specific NRG1 signaling. Our findings reveal the neural plasticity-based mechanism for ketamine-mediated functional recovery from adult amblyopia.Highlights○ Disinhibition of excitatory cells by ketamine occurs in a fast and sustained manner○ Ketamine evokes NRG1 downregulation and excitatory input loss to PV cells○ Ketamine induced plasticity is blocked by exogenous NRG1 or its receptor knockout○ PV inhibitory cells are the initial functional locus underlying ketamine’s effects

scholarly journals Exploration of sensory and spinal neurons expressing gastrin-releasing peptide in itch and pain related behaviors

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Devin M. Barry ◽  
Xue-Ting Liu ◽  
Benlong Liu ◽  
Xian-Yu Liu ◽  
Fang Gao ◽  
...  
Keyword(s):  
Spinal Neurons ◽  
Gastrin Releasing Peptide

Psychotherapy, Pharmacotherapy and Rehabilitation of a Child with Cerebral Palsy

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
E. Mojs ◽  
E. Gajewska ◽  
M.D. Głowacka ◽  
W. Samborski
Keyword(s):  
Cerebral Palsy ◽  
Clinical Symptoms ◽  
Wide Spectrum ◽  
Muscle Tension ◽  
Occupational Rehabilitation ◽  
List Type ◽  
Neural Connections ◽  
Anxiolytic Drugs ◽  
Systematic Training ◽  
Low Toxicity

Cerebral palsy (CP) is one of the most often non-progressive encephalopaties. among clinical symptoms the mobility and posture disturbances are predominantly observed, most typically neurologic and motor disturbances, showing up as spasticity, disturbances in muscle tension, ataxia or somatosensoric problems. CP and its coexisting symptoms, encompassing mental impairment are most severe causes of handicap in children and constitute an important factor deteriorating the fulfilment of developmental tasks. the improvement of the functional status depends on systematic training based on learning processes. Following training, as effect of learning, stable plastic alterations in brain occurs, based on the previously described feature of making new synaptic connections and synaptic stabilization due to apoptosis of some other neural connections. Neverless pharmacotherapy, though it cannot remove the source of the disturbances and acts mainly symptomatically, is a important element of the complex rehabilitation. However, taking into consideration the chronic and stable character of the pathologic process, it should be remembered that the pharmacologic substances used should be characterized by:•high safety,•low toxicity,•beneficial psychotropic properties,organoleptic properties accepted by children.The most frequently used drug groups in the cerebral palsy are:•tranquilizers,•anxiolytic drugs,•neuroleptics,•antidepressive drugs,•psychoenergetizing drugs, improving the brain circulation, limiting muscular tonus, - anti-epileptic drugs.Rational use of relatively wide spectrum of drugs, relaxant, sedative, anxiolytic, toning up, improving cerebral perfusion, anticonvulsory and reducing muscle tonus makes diagnostics, functional psychotherapy, kinesis therapy, ergotherapy, manual therapy, physical therapy, as well as social and occupational rehabilitation easier to a very high extent.

scholarly journals The neurokinin-1 receptor is expressed with gastrin-releasing peptide receptor in spinal interneurons and modulates itch

2020 ◽  
Author(s):  
Tayler D. Sheahan ◽  
Charles A. Warwick ◽  
Louis G. Fanien ◽  
Sarah E. Ross
Keyword(s):  
Dorsal Horn ◽  
Projection Neurons ◽  
Spinal Neurons ◽  
Neurokinin 1 Receptor ◽  
Peptide Receptor ◽  
Gastrin Releasing Peptide ◽  
Dorsal Horn Neurons ◽  
Endogenous Expression ◽  
Neurokinin 1

AbstractThe neurokinin-1 receptor (NK1R, encoded by Tacr1) is expressed in spinal dorsal horn neurons and has been suggested to mediate itch. However, previous studies relied heavily on neurotoxic ablation of NK1R spinal neurons, which limited further dissection of their function in spinal itch circuitry. Thus, we leveraged a newly developed Tacr1CreER mouse line to characterize the role of NK1R spinal neurons in itch. We show that pharmacological activation of spinal NK1R and chemogenetic activation of Tacr1CreER spinal neurons increases itch behavior, whereas pharmacological inhibition of spinal NK1R suppresses itch behavior. We use fluorescence in situ hybridization to characterize the endogenous expression of Tacr1 throughout the superficial and deeper dorsal horn, as well as the lateral spinal nucleus.Retrograde labeling studies from the parabrachial nucleus show that less than 20% of superficial Tacr1CreER dorsal horn neurons are spinal projection neurons, and thus the majority of Tacr1CreER are local interneurons. We then use a combination of in situ hybridization and ex vivo two-photon Ca2+ imaging of the spinal cord to establish that NK1R and the gastrin-releasing peptide receptor (GRPR) are coexpressed within a subpopulation of excitatory superficial dorsal horn neurons. These findings are the first to describe a role for NK1R interneurons in itch and extend our understanding of the complexities of spinal itch circuitry.

scholarly journals Exploration of Sensory and Spinal Neurons Expressing GRP in Itch and Pain

2018 ◽  
Author(s):  
Devin M. Barry ◽  
Xue-Ting Liu ◽  
Qianyi Yang ◽  
Xian-Yu Liu ◽  
Xiansi Zeng ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Nerve Fibers ◽  
List Type ◽  
Spinal Neurons ◽  
Genetic Ablation ◽  
Conditional Deletion ◽  
Pain Transmission ◽  
Chronic Pruritus ◽  
Stimulation Of

AbstractGastrin-releasing peptide (GRP) is a putative itch-specific neurotransmitter, but definite evidence in the dorsal root ganglion (DRG) and spinal cord is lacking. We generated and validated a Grp-Cre knock-in (GrpCre-KI) mouse line whereby Grp neurons are genetically labeled. Cre-dependent marking analysis revealed exclusive innervation of the upper epidermis of the skin by GRP fibers. Importantly, optical stimulation of Grp fibers expressing channel rhodopsin (ChR2) in the skin evoked itch but not pain-related scratching behaviors, while conditional deletion of Grp in sensory neurons attenuated non-histaminergic itch. In contrast, intersectional genetic ablation of spinal Grp neurons did not affect itch nor pain transmission. Our study demonstrates a role of GRP in sensory neurons in itch and suggests that GRP sensory neurons are dedicated to itch transmission. GrpCre-KI mice provide a long-sought avenue for investigating peripheral coding mechanism of itch and further interrogation of itch-nerve fibers in the skin under chronic pruritus.HighlightsValidated expression of a Grp-Cre knock-in line in sensory neurons that innervate the skinOpto-activation of Grp sensory neurons evokes itch behaviorConditional deletion of Grp in sensory neurons reduces non-histaminergic itch behaviorIntersectional ablation of Grp spinal neurons does not affect itch or pain behaviors

scholarly journals Adipokines set neural tone by regulating synapse number

2019 ◽  
Author(s):  
Ava E. Brent ◽  
Akhila Rajan
Keyword(s):  
State Energy ◽  
Inhibitory Neurons ◽  
Neuron Activity ◽  
List Type ◽  
Neuronal Function ◽  
Synaptic Contacts ◽  
Nutrient Surplus ◽  
Energy Store ◽  
Energy Sensing ◽  
Negative Tone

SummaryEnergy sensing neural circuits decide to expend or conserve resources by integrating tonic steady-state energy store information with phasic signals for hunger and food intake. Tonic signals, in the form of adipose tissue-derived adipokines, set the baseline level of energy-sensing neuron activity, providing context for interpretation of phasic messages. However, the mechanism by which tonic adipokine information establishes baseline neuronal function is unclear. Here we show that Upd2, a Drosophila Leptin ortholog, regulates actin-based synapse reorganization by reducing inhibitory synaptic contacts, thereby providing a permissive neural tone for insulin release under conditions of nutrient surplus. Unexpectedly, Insulin acts on the same upstream inhibitory neurons to conversely increase synapse number, hence re-instating negative tone. Our results suggest that two surplus-sensing hormonal systems, Leptin/Upd2 and Insulin, converge on a neuronal circuit with opposing outcomes that establish tonic, energy-store-dependent neuron activity.HighlightsThe adipokine Upd2 regulates number of inhibitory synaptic contacts on Insulin neurons.Upd2 activates an actin-regulating complex of Arouser, Basigin, and Gelsolin in target neurons.Arouser, Basigin, and Gelsolin reduce the extent of inhibitory contact on Insulin neurons.Insulin resets negative tone by increasing the number of synaptic contacts made by its own upstream inhibitory neurons.

scholarly journals Primary visual cortex injury produces loss of inhibitory neurons and long-term visual circuit dysfunction

2020 ◽  
Author(s):  
Jan C. Frankowski ◽  
Andrzej T. Foik ◽  
Jiana R. Machhor ◽  
David C. Lyon ◽  
Robert F. Hunt
Keyword(s):  
Visual Cortex ◽  
Primary Visual Cortex ◽  
Traumatic Injury ◽  
Cortical Inhibition ◽  
Inhibitory Neurons ◽  
List Type ◽  
V1 Neurons ◽  
Adult Mice ◽  
Brain Injured ◽  
The Impact

SummaryPrimary sensory areas of the mammalian neocortex have a remarkable degree of plasticity, allowing neural circuits to adapt to dynamic environments. However, little is known about the effect of traumatic brain injury on visual system function. Here we applied a mild focal contusion injury to primary visual cortex (V1) in adult mice. We found that, although V1 was largely intact in brain-injured mice, there was a reduction in the number of inhibitory interneurons that extended into deep cortical layers. In general, we found a preferential reduction of interneurons located in superficial layers, near the impact site, while interneurons positioned in deeper layers were better preserved. Three months after injury, V1 neurons showed dramatically reduced responses to visual stimuli and weaker orientation selectivity and tuning, consistent with the loss of cortical inhibition. Our results demonstrate that V1 neurons no longer robustly and stably encode visual input following a mild traumatic injury.HighlightsInhibitory neurons are lost throughout brain injured visual cortexVisually-evoked potentials are severely degraded after injuryInjured V1 neurons show weaker selectivity and tuning consistent with reduced interneurons

scholarly journals A kernel-based method to calculate local field potentials from networks of spiking neurons

2020 ◽  
Author(s):  
Bartosz Telenczuk ◽  
Maria Telenczuk ◽  
Alain Destexhe
Keyword(s):  
Local Field ◽  
Pyramidal Neurons ◽  
Field Potential ◽  
Point Of View ◽  
Spiking Neurons ◽  
Inhibitory Neurons ◽  
List Type ◽  
Synaptic Currents ◽  
Hippocampal Pyramidal Neurons ◽  
Low Pass

AbstractBackgroundThe local field potential (LFP) is usually calculated from current sources arising from transmembrane currents, in particular in asymmetric cellular morphologies such as pyramidal neurons.New methodHere, we adopt a different point of view and relate the spiking of neurons to the LFP through efferent synaptic connections and provide a method to calculate LFPs.ResultsWe show that the so-called unitary LFPs (uLFP) provide the key to such a calculation. We show experimental measurements and simulations of uLFPs in neocortex and hippocampus, for both excitatory and inhibitory neurons. We fit a “kernel” function to measurements of uLFPs, and we estimate its spatial and temporal spread by using simulations of morphologically detailed reconstructions of hippocampal pyramidal neurons. Assuming that LFPs are the sum of uLFPs generated by every neuron in the network, the LFP generated by excitatory and inhibitory neurons can be calculated by convolving the trains of action potentials with the kernels estimated from uLFPs. This provides a method to calculate the LFP from networks of spiking neurons, even for point neurons for which the LFP is not easily defined. We show examples of LFPs calculated from networks of point neurons and compare to the LFP calculated from synaptic currents.ConclusionsThe kernel-based method provides a practical way to calculate LFPs from networks of point neurons.HighlightsWe provide a method to estimate the LFP from spiking neuronsThis method is based on kernels, estimated from experimental dataWe show applications of this method to calculate the LFP from networks of spiking neuronsWe show that the kernel-based method is a low-pass filtered version of the LFP calculated from synaptic currents

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