161 Optogenetic Stimulation of Cerebellar Dentate Nucleus Promotes Persistent Functional Recovery After Stroke

Neurosurgery ◽  
2015 ◽  
Vol 62 ◽  
pp. 218-219
Author(s):  
Shunsuke Ishizaka ◽  
Michelle Cheng ◽  
Aatman M. Shah ◽  
Eric Wang ◽  
Alex R. Bautista ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Dentate Nucleus ◽  
Optogenetic Stimulation ◽  
Cerebellar Dentate Nucleus ◽  
Stimulation Of

scholarly journals Optogenetic Stimulation Reduces Neuronal Nitric Oxide Synthase Expression After Stroke

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Arjun Vivek Pendharkar ◽  
Daniel L Smerin ◽  
Lorenzo Gonzales ◽  
Eric Wang ◽  
Sabrina L Levy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Motor Cortex ◽  
Functional Recovery ◽  
Neuronal Nitric Oxide Synthase ◽  
Optogenetic Stimulation ◽  
Oxide Synthase ◽  
Nnos Expression ◽  
Stimulation Of ◽  
Nnos Inhibition

Abstract INTRODUCTION Poststroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of neurovascular response in acute stroke but its role in subacute recovery remains unclear. Here we investigate nNOS expression in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examine the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. METHODS Transgenic Thy1-ChR2-YFP male mice (10-12 wk) were used. Stereotaxic surgery was performed to implant a fiber cannula in the cLCN and animals underwent intraluminal middle cerebral artery suture occlusion (30 min). Optogenetic stimulation began at poststroke (PD) day 5 and continued until PD14. Sensorimotor tests were used to assess behavioral recovery at PD4, 7, 10, and 14. At PD15, primary motor cortex from both ipsi- and contralesional motor cortex (iM1, cM1) were dissected. nNOS mRNA and protein levels were examined using quantitative polymerase chain reaction and western blot. In another set of studies, nNOS inhibitor ARL 17477 dihydrochloride (10 mg/kg, intraperitoneally) was administered daily between PD5-14 and functional recovery was evaluated using sensorimotor tests. RESULTS cLCN stimulated stroke mice demonstrated significant improvement in speed (cm/s) on the rotating beam task at PD10 and 14 day (P < .05, P < .001 respectively). nNOS mRNA and protein expression was significantly and selectively decreased in cM1 of cLCN stimulated mice (P < .05). The reduced nNOS expression in cM1 was negatively correlated with improved recovery (R2 = −0.839, Pearson P = .009). nNOS inhibitor-treated stroke mice exhibited a significant functional improvement in speed at PD10, when compared to stroke mice receiving vehicle (saline) (P < .05). CONCLUSION Our results suggest that nNOS may play a maladaptive role in poststroke recovery. Optogenetic stimulation of cLCN and systemic nNOS inhibition produce functional benefits after stroke.

193 Optogenetic Stimulation of Motor Cortex Neurons Promotes Functional Recovery After Stroke

Neurosurgery ◽  
2013 ◽  
Vol 60 ◽  
pp. 184
Author(s):  
Michelle Cheng ◽  
Wyatt J. Woodson ◽  
Eric Wang ◽  
Stephanie Wang ◽  
GuoHua Sun ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Functional Recovery ◽  
Optogenetic Stimulation ◽  
Stimulation Of

scholarly journals Brain-wide neural dynamics of poststroke recovery induced by optogenetic stimulation

2021 ◽  
Vol 7 (33) ◽  
pp. eabd9465
Author(s):  
Shahabeddin Vahdat ◽  
Arjun Vivek Pendharkar ◽  
Terrance Chiang ◽  
Sean Harvey ◽  
Haruto Uchino ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Primary Motor Cortex ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Neural Dynamics ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Optogenetic Stimulation ◽  
Important Mediator ◽  
Stimulation Of

Poststroke optogenetic stimulations can promote functional recovery. However, the circuit mechanisms underlying recovery remain unclear. Elucidating key neural circuits involved in recovery will be invaluable for translating neuromodulation strategies after stroke. Here, we used optogenetic functional magnetic resonance imaging to map brain-wide neural circuit dynamics after stroke in mice treated with and without optogenetic excitatory neuronal stimulations in the ipsilesional primary motor cortex (iM1). We identified key sensorimotor circuits affected by stroke. iM1 stimulation treatment restored activation of the ipsilesional corticothalamic and corticocortical circuits, and the extent of activation was correlated with functional recovery. Furthermore, stimulated mice exhibited higher expression of axonal growth–associated protein 43 in the ipsilesional thalamus and showed increased Synaptophysin+/channelrhodopsin+ presynaptic axonal terminals in the corticothalamic circuit. Selective stimulation of the corticothalamic circuit was sufficient to improve functional recovery. Together, these findings suggest early involvement of corticothalamic circuit as an important mediator of poststroke recovery.

scholarly journals Organization of Excitatory Inputs from the Cerebral Cortex to the Cerebellar Dentate Nucleus

1993 ◽  
Vol 20 (S3) ◽  
pp. S19-S28 ◽  
Author(s):  
Shinoda Yoshikazu ◽  
Sugiuchi Yuriko ◽  
Futami Takahiro
Keyword(s):  
Cerebral Cortex ◽  
Dentate Nucleus ◽  
Inferior Olive ◽  
Mossy Fibers ◽  
Excitatory Input ◽  
Control Mechanisms ◽  
Pontine Nucleus ◽  
Pericruciate Cortex ◽  
Cerebellar Dentate Nucleus ◽  
Stimulation Of

ABSTRACT:Intracellular recording was made from dentate nucleus neurons (DNNs) in anesthetized cats, to investigate cerebral inputs to DNNs and their responsible pathways. Stimulation of the medial portion of the contralateral pericruciate cortex most effectively produced EPSPs followed by long-lasting IPSPs in DNNs. Stimulation of the pontine nucleus (PN), the nucleus reticularis tegmenti pontis (NRTP) and the inferior olive (IO) produced monosynaptic EPSPs and polysynaptic IPSPs in DNNs. The results indicate that the excitatory input from the cerebral cortex to DNNs is at least partly relayed via the PN, the NRTP and the 10. Intraaxonal injection of HRP visualized the morphology of mossy fibers from the PN to the DN and the cerebellar cortex. The functional significance of the excitatory inputs from the PN and the NRTP to the DN is discussed in relation to the motor control mechanisms of the cerebellum.

Abstract 24: Optogenetic Stimulation of Excitatory Motor Cortex Neurons Promotes Functional Recovery After Stroke

Stroke ◽  
2019 ◽  
Vol 50 (Suppl_1) ◽  
Author(s):  
Arjun V Pendharkar ◽  
Sean S Harvey ◽  
Terrance Chiang ◽  
Michelle Y Cheng ◽  
Gary K Steinberg
Keyword(s):  
Motor Cortex ◽  
Functional Recovery ◽  
Optogenetic Stimulation ◽  
Stimulation Of

Combining Optogenetic Stimulation and Motor Training Improves Functional Recovery and Perilesional Cortical Activity

2021 ◽  
pp. 154596832110566
Author(s):  
Emilia Conti ◽  
Alessandro Scaglione ◽  
Giuseppe de Vito ◽  
Francesco Calugi ◽  
Maria Pasquini ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Combined Therapy ◽  
Motor Training ◽  
Motor Representation ◽  
Rehabilitative Treatment ◽  
Optogenetic Stimulation ◽  
Temporal Features ◽  
Spatio Temporal ◽  
Motor Representations ◽  
Stimulation Of

Background. An ischemic stroke is followed by the remapping of motor representation and extensive changes in cortical excitability involving both hemispheres. Although stimulation of the ipsilesional motor cortex, especially when paired with motor training, facilitates plasticity and functional restoration, the remapping of motor representation of the single and combined treatments is largely unexplored. Objective. We investigated if spatio-temporal features of motor-related cortical activity and the new motor representations are related to the rehabilitative treatment or if they can be specifically associated to functional recovery. Methods. We designed a novel rehabilitative treatment that combines neuro-plasticizing intervention with motor training. In detail, optogenetic stimulation of peri-infarct excitatory neurons expressing Channelrhodopsin 2 was associated with daily motor training on a robotic device. The effectiveness of the combined therapy was compared with spontaneous recovery and with the single treatments (ie optogenetic stimulation or motor training). Results. We found that the extension and localization of the new motor representations are specific to the treatment, where most treatments promote segregation of the motor representation to the peri-infarct region. Interestingly, only the combined therapy promotes both the recovery of forelimb functionality and the rescue of spatio-temporal features of motor-related activity. Functional recovery results from a new excitatory/inhibitory balance between hemispheres as revealed by the augmented motor response flanked by the increased expression of parvalbumin positive neurons in the peri-infarct area. Conclusions. Our findings highlight that functional recovery and restoration of motor-related neuronal activity are not necessarily coupled during post-stroke recovery. Indeed the reestablishment of cortical activation features of calcium transient is distinctive of the most effective therapeutic approach, the combined therapy.

scholarly journals Incerto-thalamic modulation of fear via GABA and dopamine

2021 ◽  
Author(s):  
Archana Venkataraman ◽  
Sarah C. Hunter ◽  
Maria Dhinojwala ◽  
Diana Ghebrezadik ◽  
JiDong Guo ◽  
...  
Keyword(s):  
Brain Regions ◽  
Zona Incerta ◽  
Dependent Manner ◽  
Post Traumatic Stress ◽  
Functional Roles ◽  
Functional Connections ◽  
Optogenetic Stimulation ◽  
Fear Generalization ◽  
Stimulation Of

AbstractFear generalization and deficits in extinction learning are debilitating dimensions of Post-Traumatic Stress Disorder (PTSD). Most understanding of the neurobiology underlying these dimensions comes from studies of cortical and limbic brain regions. While thalamic and subthalamic regions have been implicated in modulating fear, the potential for incerto-thalamic pathways to suppress fear generalization and rescue deficits in extinction recall remains unexplored. We first used patch-clamp electrophysiology to examine functional connections between the subthalamic zona incerta and thalamic reuniens (RE). Optogenetic stimulation of GABAergic ZI → RE cell terminals in vitro induced inhibitory post-synaptic currents (IPSCs) in the RE. We then combined high-intensity discriminative auditory fear conditioning with cell-type-specific and projection-specific optogenetics in mice to assess functional roles of GABAergic ZI → RE cell projections in modulating fear generalization and extinction recall. In addition, we used a similar approach to test the possibility of fear generalization and extinction recall being modulated by a smaller subset of GABAergic ZI → RE cells, the A13 dopaminergic cell population. Optogenetic stimulation of GABAergic ZI → RE cell terminals attenuated fear generalization and enhanced extinction recall. In contrast, optogenetic stimulation of dopaminergic ZI → RE cell terminals had no effect on fear generalization but enhanced extinction recall in a dopamine receptor D1-dependent manner. Our findings shed new light on the neuroanatomy and neurochemistry of ZI-located cells that contribute to adaptive fear by increasing the precision and extinction of learned associations. In so doing, these data reveal novel neuroanatomical substrates that could be therapeutically targeted for treatment of PTSD.

scholarly journals Involvement of MCH-oxytocin neural relay within the hypothalamus in murine nursing behavior

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoko Kato ◽  
Harumi Katsumata ◽  
Ayumu Inutsuka ◽  
Akihiro Yamanaka ◽  
Tatsushi Onaka ◽  
...  
Keyword(s):  
Mammalian Species ◽  
Virgin Female ◽  
Essential Elements ◽  
Hypothalamic Nucleus ◽  
Male Mice ◽  
Hypothalamic Area ◽  
Functional Roles ◽  
Genetic Ablation ◽  
Optogenetic Stimulation ◽  
Stimulation Of

AbstractMultiple sequential actions, performed during parental behaviors, are essential elements of reproduction in mammalian species. We showed that neurons expressing melanin concentrating hormone (MCH) in the lateral hypothalamic area (LHA) are more active in rodents of both sexes when exhibiting parental nursing behavior. Genetic ablation of the LHA-MCH neurons impaired maternal nursing. The post-birth survival rate was lower in pups born to female mice with congenitally ablated MCH neurons under control of tet-off system, exhibiting reduced crouching behavior. Virgin female and male mice with ablated MCH neurons were less interested in pups and maternal care. Chemogenetic and optogenetic stimulation of LHA-MCH neurons induced parental nursing in virgin female and male mice. LHA-MCH GABAergic neurons project fibres to the paraventricular hypothalamic nucleus (PVN) neurons. Optogenetic stimulation of PVN induces nursing crouching behavior along with increasing plasma oxytocin levels. The hypothalamic MCH neural relays play important functional roles in parental nursing behavior in female and male mice.

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