scholarly journals Longitudinal functional imaging of VIP interneurons reveals sup-population specific effects of stroke that are rescued with chemogenetic therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mohamad Motaharinia ◽  
Kim Gerrow ◽  
Roobina Boghozian ◽  
Emily White ◽  
Sun-Eui Choi ◽  
...  
Keyword(s):  
Calcium Imaging ◽  
Cortical Excitability ◽  
Sensory Response ◽  
Inhibitory Interneurons ◽  
Partial Recovery ◽  
Highly Active ◽  
Specific Effects ◽  
Somatosensory Responses ◽  
Photothrombotic Stroke ◽  
Sensory Responses

AbstractStroke profoundly disrupts cortical excitability which impedes recovery, but how it affects the function of specific inhibitory interneurons, or subpopulations therein, is poorly understood. Interneurons expressing vasoactive intestinal peptide (VIP) represent an intriguing stroke target because they can regulate cortical excitability through disinhibition. Here we chemogenetically augmented VIP interneuron excitability in a murine model of photothrombotic stroke and show that it enhances somatosensory responses and improves recovery of paw function. Using longitudinal calcium imaging, we discovered that stroke primarily disrupts the fidelity (fraction of responsive trials) and predictability of sensory responses within a subset of highly active VIP neurons. Partial recovery of responses occurred largely within these active neurons and was not accompanied by the recruitment of minimally active neurons. Importantly, chemogenetic stimulation preserved sensory response fidelity and predictability in highly active neurons. These findings provide a new depth of understanding into how stroke and prospective therapies (chemogenetics), can influence subpopulations of inhibitory interneurons.

Longitudinal imaging of VIP interneurons reveals sup-population specific effects of stroke that can be rescued with chemogenetic therapy

2021 ◽  
Author(s):  
Mohamad Motaharinia ◽  
Kimberly Gerrow ◽  
Roobina Boghozian ◽  
Emily White ◽  
Sun-Eui Choi ◽  
...  
Keyword(s):  
Calcium Imaging ◽  
Cortical Excitability ◽  
Sensory Response ◽  
Inhibitory Interneurons ◽  
Partial Recovery ◽  
Highly Active ◽  
Specific Effects ◽  
Somatosensory Responses ◽  
Sensory Responses ◽  
Longitudinal Imaging

Abstract Stroke profoundly disrupts cortical excitability which impedes recovery, but how it affects the function of specific inhibitory interneurons, or subpopulations therein, is poorly understood. Interneurons expressing vasoactive intestinal peptide (VIP) represent an intriguing stroke target because they can regulate cortical excitability through disinhibition. Here we chemogenetically augmented VIP interneuron excitability after stroke to show that it enhances somatosensory responses and improves recovery of paw function. Using longitudinal calcium imaging, we discovered that stroke primarily disrupts the fidelity (fraction of responsive trials) and predictability of sensory responses within a subset of highly active VIP neurons. Partial recovery of responses occurred largely within these active neurons and was not accompanied by the recruitment of minimally active neurons. Importantly, chemogenetic stimulation preserved sensory response fidelity and predictability in highly active neurons. These findings provide a new depth of understanding into how stroke and prospective therapies (chemogenetics), can influence subpopulations of inhibitory interneurons.

Facilitating Sensory Responses in Developing Mouse Somatosensory Barrel Cortex

2007 ◽  
Vol 97 (4) ◽  
pp. 2992-3003 ◽  
Author(s):  
Aren J. Borgdorff ◽  
James F. A. Poulet ◽  
Carl C. H. Petersen
Keyword(s):  
Barrel Cortex ◽  
Cortical Excitability ◽  
Sensory Response ◽  
Cortical Circuits ◽  
Pharmacological Agents ◽  
Sensory Stimuli ◽  
Early Postnatal Development ◽  
Sensory Responses ◽  
Activity Dependent ◽  
Whole Cell Recordings

The sensory responses in the barrel cortex of mice aged postnatal day (P)7–P12 evoked by a single whisker deflection are smaller in amplitude and spread over a smaller area than those measured in P13–P21 mice. However, repetitive 10-Hz stimulation or paired pulse whisker stimulation in P7–P12 mice evoked facilitating sensory responses, contrasting with the depressing sensory responses observed in P13–P21 mice. This facilitation occurred during an interval ranging 300–1,000 ms after the first stimulus and was measured using whole cell recordings, voltage-sensitive dye imaging, and calcium-sensitive dye imaging. The facilitated responses were not only larger in amplitude but also propagated over a larger cortical area. The facilitation could be blocked by local application of pharmacological agents reducing cortical excitability. Local cortical microstimulation could substitute for the first whisker stimulus to produce a facilitated sensory response. The enhanced sensory responses evoked by repetitive sensory stimuli in P7–P12 mice may contribute to the activity-dependent specification of the developing cortical circuits. In addition, the facilitating sensory responses allow long integration times for sensory processing compatible with the slow behavior of mice during early postnatal development.

Sleep deprivation increases cortical excitability in epilepsy: Syndrome-specific effects

Neurology ◽  
2006 ◽  
Vol 67 (6) ◽  
pp. 1018-1022 ◽  
Author(s):  
R.A.B. Badawy ◽  
J. M. Curatolo ◽  
M. Newton ◽  
S. F. Berkovic ◽  
R. A.L. Macdonell
Keyword(s):  
Sleep Deprivation ◽  
Cortical Excitability ◽  
Epilepsy Syndrome ◽  
Specific Effects

Mechanosensory properties in the human gastric antrum evaluated using B-mode ultrasonography during volume-controlled antral distension

2006 ◽  
Vol 290 (5) ◽  
pp. G876-G882 ◽  
Author(s):  
H. Gregersen ◽  
T. Hausken ◽  
J. Yang ◽  
S. Ødegaard ◽  
O. H. Gilja
Keyword(s):  
Anticholinergic Drug ◽  
Muscle Length ◽  
Gastric Antrum ◽  
Variation Coefficient ◽  
Sensory Response ◽  
Pressure Amplitude ◽  
Sensory Responses ◽  
Volume Controlled ◽  
Antral Distension

The aims of this study were to evaluate gastric antral mechanical behavior and distension-induced sensorimotor responses in the human gastric antrum using transabdominal ultrasound scanning. Ten healthy volunteers underwent volume-controlled ramp inflation of a bag located in the antrum with volumes up to 125 ml. The active and passive circumferential tensions and stresses were calculated from measurements of pressure, diameter, and wall thickness before and during the administration of the anticholinergic drug butylscopolamine. The bag distensions elicited contractions in the antrum and sensory responses below the pain threshold. Butylscopolamine abolished the contractions and significantly reduced the sensory response. The length-tension diagram known from in vitro studies of smooth muscle strips could be reproduced as tension-volume diagrams in the human gastric antrum. The number of induced contractions and the contraction pressure amplitude (afterload) showed a parabolic behavior as function of the distension volume (preload), with maximum approximately at 70 ml. At the sensation threshold, the luminal circumference showed the lowest variation coefficient (13–25%), whereas the variation coefficient was more than 100% for the pressure, tensions, and stresses. We conclude that the muscle length-tension diagram and typical preload-afterload curves ad modem the Frank-Starling cardiac law can be obtained in the human gastric antrum. The sensory responses were most closely associated with the luminal circumference, indicating that the sensation during antral distension depends on deformation rather than on tension.

Chronic Suppression of Activity in Barrel Field Cortex Downregulates Sensory Responses in Contralateral Barrel Field Cortex

2005 ◽  
Vol 94 (5) ◽  
pp. 3342-3356 ◽  
Author(s):  
Lu Li ◽  
V. Rema ◽  
Ford F. Ebner
Keyword(s):  
Barrel Cortex ◽  
Cortical Excitability ◽  
Single Cells ◽  
Cortical Function ◽  
Adult Rats ◽  
Strong Suppression ◽  
Barrel Field ◽  
Layer V ◽  
Sensory Responses ◽  
Prominent Response

Numerous lines of evidence indicate that neural information is exchanged between the cerebral hemispheres via the corpus callosum. Unilateral ablation lesions of barrel field cortex (BFC) in adult rats induce strong suppression of background and evoked activity in the contralateral barrel cortex and significantly delay the onset of experience-dependent plasticity. The present experiments were designed to clarify the basis for these interhemispheric effects. One possibility is that degenerative events, triggered by the lesion, degrade contralateral cortical function. Another hypothesis, alone or in combination with degeneration, is that the absence of interhemispheric activity after the lesion suppresses contralateral responsiveness. The latter hypothesis was tested by placing an Alzet minipump subcutaneously and connecting it via a delivery tube to a cannula implanted over BFC. The minipump released muscimol, a GABAA receptor agonist at a rate of 1 μl/h, onto one barrel field cortex for 7 days. Then with the pump still in place, single cells were recorded in the contralateral BFC under urethan anesthesia. The data show a ∼50% reduction in principal whisker responses (D2) compared with controls, with similar reductions in responses to the D1 and D3 surround whiskers. Despite these reductions, spontaneous firing is unaffected. Fast spiking units are more sensitive to muscimol application than regular spiking units in both the response magnitude and the center/surround ratio. Effects of muscimol are also layer specific. Layer II/III and layer IV neurons decrease their responses significantly, unlike layer V neurons that fail to show significant deficits. The results indicate that reduced activity in one hemisphere alters cortical excitability in the other hemisphere in a complex manner. Surprisingly, a prominent response decrement occurs in the short-latency (3–10 ms) component of principal whisker responses, suggesting that suppression may spread to neurons dominated by thalamocortical inputs after interhemispheric connections are inactivated. Bilateral neurological impairments have been described after unilateral stroke lesions in the clinical literature.

scholarly journals GFAPα IgG-associated encephalitis upon daclizumab treatment of MS

2018 ◽  
Vol 5 (5) ◽  
pp. e481 ◽  
Author(s):  
Felix Luessi ◽  
Sinah Engel ◽  
Annette Spreer ◽  
Stefan Bittner ◽  
Frauke Zipp
Keyword(s):  
Clinical Symptoms ◽  
Age At Onset ◽  
Antibody Therapy ◽  
Partial Recovery ◽  
Brain Disorders ◽  
Igg Antibodies ◽  
Protein Levels ◽  
Highly Active ◽  
Cns Autoimmunity ◽  
American Case

ObjectiveTo describe a case of glial fibrillary acidic protein (GFAP)α immunoglobulin G (IgG)-associated encephalitis in a patient referred to us with MS on daclizumab treatment and to summarize characteristics of 5 additional recent German MS cases of serious encephalitis along with a previously published American case of CNS vasculitis associated with daclizumab.MethodsEvaluation of cause, clinical symptoms, and treatment response.ResultsThe 6 patients included 4 women and 2 men. The median age at onset was 38 years (range 32–51 years). Clinical presentation was marked by progressing neuropsychologic and/or neurologic deficits. Additional drug rash with eosinophilia was seen in 3 patients, whereas 2 patients showed a highly active demyelinating process. Examination of CSF samples detected pleocytosis, elevated total protein levels, and GFAPα IgG antibodies, which were not found in serum. In our case, we discovered autoimmune GFAP astrocytopathy associated with encephalitis as secondary autoimmunity, which was steroid responsive. Clinical outcome of other cases was marked by partial recovery in 4 patients and persistent foster care in 1 patient.ConclusionsOur case of GFAPα IgG-associated encephalitis along with 12 other cases of serious inflammatory brain disorders following daclizumab treatment so far indicates that interfering with NK cells and Tregs by anti-CD25 antibody therapy can result in severe secondary CNS autoimmunity in man.

scholarly journals Parallel lemniscal and non-lemniscal sources control auditory responses in the orbitofrontal cortex (OFC)

2020 ◽  
Author(s):  
Hemant K Srivastava ◽  
Sharba Bandyopadhyay
Keyword(s):  
Orbitofrontal Cortex ◽  
Sensory Response ◽  
Persistent Activity ◽  
Response Properties ◽  
Auditory Thalamus ◽  
Deviance Detection ◽  
Auditory Responses ◽  
Sensory Responses ◽  
Behavioral Requirement ◽  
Long Timescales

AbstractThe orbitofrontal cortex (OFC), controls flexible behavior through stimulus value updating based on stimulus outcome associations, allowing seamless navigation in dynamic sensory environments with changing contingencies. Sensory cue driven responses, primarily studied through behavior, exist in the OFC. However, OFC neurons’ sensory response properties, particularly auditory, are unknown, in the mouse, a genetically tractable animal. We show that mouse OFC single neurons have unique auditory response properties showing pure deviance detection and long timescales of adaptation resulting in stimulus-history dependence. Further, we show that OFC auditory responses are shaped by two parallel sources in the auditory thalamus, lemniscal and non-lemniscal. The latter underlies a large component of the observed deviance detection and additionally controls persistent activity in the OFC through the amygdala. The deviant selectivity can serve as a signal for important changes in the auditory environment. Such signals if coupled with persistent activity, obtained by disinhibitory control from the non-lemniscal auditory thalamus or the amygdala, will allow for associations with a delayed outcome related signal, like reward prediction error, and potentially forms the basis of updating stimulus outcome associations in the OFC. Thus the baseline sensory responses allow the behavioral requirement based response modification through relevant inputs from other structures related to reward, punishment, or memory. Thus, alterations in these responses in neurological disorders can lead to behavioral deficits.

scholarly journals A study to further develop and refine carpal tunnel syndrome (CTS) nerve conduction grading tool

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Salim Hirani
Keyword(s):  
Carpal Tunnel Syndrome ◽  
Carpal Tunnel ◽  
Nerve Conduction ◽  
Sensory Response ◽  
Grading System ◽  
Grading Systems ◽  
Sensory Motor ◽  
Tunnel Syndrome ◽  
Sensory Changes ◽  
Sensory Responses

Abstract Background The severity of carpal tunnel syndrome (CTS) may be categorised in a number of ways utilising one of a range of presently available grading tools. The grading systems proposed by Bland and Padua are the most commonly used, however, both have limitations, which are discussed in detail in this paper. The aim of this research is to establish, using the best available evidence, a clinically appropriate revision of the current CTS nerve conduction grading tool, and to compare with existing grading tools used in UK Neurophysiology clinics. The revised scale is designed from a clinical physiologist perspective and based on the numerical values of nerve conduction findings. The proposed revised grading system is based on more nuanced, descriptive categories, ranging from Normal to Early, Mild Sensory, Mild Sensory Motor, Moderate Sensory, Moderate Sensory Motor, Severe Sensory Motor, Extremely Severe Sensory Motor, and Complete absence. Method A total of 1123 patients (2246 hands) were included in this study, with the aim of evaluating the revised grading system. Data was collected based on the extensive and detailed grading systems previously described by Bland and Padua. All data was recorded numerically to ensure methodological reliability. Result Of the 2246 patients’ hands tested, the nerve conduction was graded as normal in 968 hands; nerve conduction showed early changes in 271 hands; mild sensory changes in 215 hands, mild changes in both motor and sensory response in 51 hands; moderate sensory changes in 134 hands; moderate sensory and motor changes in 356 hands; severe changes in motor and sensory responses in 204 hands; extremely severe sensory and motor changes in 33 hands and complete absence of response in 14 hands. Conclusion The revised grading tool could offer a more numerical grading to the Clinical Physiologist and could help the surgeon to ascertain the level of severity in order to decide on either a conservative or surgical approach to treatment if they decide to use the proposed grading which could support them to defend their decision in cases of litigation.

Abstract TMP34: Longitudinal Calcium Imaging Reveals Circuit Switching and Abnormal Response Fidelity in Somatosensory Vip Interneuron Circuits in the Stroke Damaged Brain

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Craig E Brown ◽  
Mohammad Motaharinia
Keyword(s):  
Critical Role ◽  
Significant Loss ◽  
Inhibitory Neurons ◽  
Circuit Switching ◽  
Highly Active ◽  
Cortical Interneurons ◽  
Before And After ◽  
Sensory Responses ◽  
Sensory Evoked ◽  
And Function

Although inhibitory cortical interneurons play a critical role in regulating brain excitability and function, the effects of stroke on these neurons is poorly understood. In particular, interneurons expressing vasoactive intestinal peptide (VIP) specialize in inhibiting other classes of inhibitory neurons, and thus serve to modulate cortical sensory processing. To understand how stroke affects this circuit, we imaged VIP neuron structure and function (using GCaMP6s) before and after focal stroke in forelimb somatosensory cortex. Stroke led to a significant loss of peri-infarct pre-synaptic boutons and dendritic spines that was followed by a wave of bouton/spine production. Larger-scale changes, such as pruning/growth of axons or dendritic branches was observed, albeit on a limited scale. Functionally, the fraction of forelimb responsive VIP interneurons and their response fidelity (defined as the % of forelimb responsive trials) was significantly reduced in the first week after stroke. The loss of responsiveness was most evident in highly active VIP neurons (defined by their level of responsiveness before stroke), whereas less active neurons were minimally affected. Of note, a small fraction of VIP neurons that were minimally active before stroke, became responsive afterwards suggesting that stroke may unmask sensory responses in some neurons. Although VIP responses to forepaw stimulation generally improved although not fully from 2-5 weeks recovery, the variance in response fidelity after stroke was comparatively high and therefore less predictable than that observed before stroke. Lastly, stroke related changes to synaptic structure and response properties were both restricted to within 400μm of the infarct border. These findings reveal the dynamic and resilient nature of VIP neurons and suggest that a sub-population of these cells are more apt to lose sensory responsiveness during the initial phase of stroke, whereas some minimally responsive cells are progressively recruited into the forelimb sensory circuit. Furthermore, stroke appears to disrupt the predictability of sensory evoked responses in these cortical interneurons which could have important consequences for sensory perception.

scholarly journals Cellular Mechanisms of Suppressive Interactions Between Somatosensory Responses In Vivo

2007 ◽  
Vol 97 (1) ◽  
pp. 647-658 ◽  
Author(s):  
Michael J. Higley ◽  
Diego Contreras
Keyword(s):  
Cellular Mechanisms ◽  
Sensory Stimuli ◽  
Cellular Processes ◽  
Neural Integration ◽  
Perceptual Representations ◽  
Integration Mechanisms ◽  
Somatosensory Responses ◽  
Multiple Levels ◽  
Sensory Responses

The neural integration of afferent inputs evoked by spatiotemporally distributed sensory stimuli is a critical step in the formation of coherent and continuous perceptual representations. Integration mechanisms in various systems include linear and nonlinear summation of sensory responses. One well-known example in the rat barrel system is the suppressive interaction between responses to the consecutive deflection of neighboring whiskers. The mechanism underlying cross-whisker suppression has long been postulated to rely on intracortical postsynaptic inhibition, although this hypothesis has been challenged by recent reports. Here we show, using intracellular and extracellular recordings in vivo, that cross-whisker suppression occurs in the absence of cortical activity. Instead, suppression arises from local circuit operations at multiple levels of the subcortical afferent pathway and is amplified by the nonlinear transformation of synaptic input into spike output in both the thalamus and cortex. Because these cellular processes are common to neural circuits subserving visual and auditory modalities, we propose that the suppressive mechanisms elucidated here are a general property of thalamocortical sensory systems.

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