scholarly journals Selective Optogenetic Stimulation of Glutamatergic, but not GABAergic, Vestibular Nuclei Neurons Induces Immediate and Reversible Postural Imbalance in Mice

2020 ◽  
Author(s):  
Q. Montardy ◽  
M. Wei ◽  
T. Yi ◽  
X. Liu ◽  
Z. Zhou ◽  
...  
Keyword(s):  
Vestibular Nuclei ◽  
Gabaergic Neurons ◽  
Support Surface ◽  
List Type ◽  
Optogenetic Stimulation ◽  
Short Period ◽  
Locomotor Deficits ◽  
Locomotor Behaviors ◽  
Stimulation Of

AbstractGlutamatergic and GABAergic neurons represent the neural components of the medial vestibular nuclei. We assessed the functional role of glutamatergic and GABAergic neuronal pathways arising from the vestibular nuclei (VN) in the maintenance of gait and balance by optogenetically stimulating the VN in VGluT2-cre and GAD2-cre mice. We demonstrate that glutamatergic, but not GABAergic VN neuronal subpopulation is responsible for immediate and strong posturo-locomotor deficits, comparable to unilateral vestibular deafferentation models. During optogenetic stimulation, the support surface dramatically increased in VNVGluT2+ mice, and rapidly fell back to baseline after stimulation, whilst it remained unchanged during similar stimulation of VNGAD2+ mice. This effect persisted when vestibular compensation was removed. Posturo-locomotor alterations evoked in VNVGluT2+ animals were still present immediately after stimulation, while they disappeared 1h later. Overall, these results indicate a fundamental role for VNVGluT2+ neurons in balance and posturo-locomotor functions, but not for VNGAD2+ neurons, in this specific context. This new optogenetic approach will be useful to characterize the role of the different VN neuronal populations involved in vestibular physiology and pathophysiology.HighlightsFor the first time, Vestibular nuclei were optogenetically stimulated in free-moving animals, to asses for glutamatergic and GABAergic neurons functions in posturo-locomotor behaviors.Brief optogenetic activation of VNVGluT2+, but not VNGAD2+, induced immediate and strong postural deficit.Stimulation of VNVGluT2+ neurons provoked an imbalance with continuous effect on locomotion for a short period of time after stimulation.These results are comparable to the classical vestibular deafferentation models during their peak of deficit, and set optogenetic stimulation as a new model to study vestibular deficits.

scholarly journals Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway

2020 ◽  
Author(s):  
Ya-Dong Li ◽  
Yan-Jia Luo ◽  
Wei Xu ◽  
Jing Ge ◽  
Yoan Cherasse ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Gabaergic Neurons ◽  
Population Activity ◽  
Lateral Habenula ◽  
Optogenetic Stimulation ◽  
Ventral Tegmental ◽  
Stimulation Of

Abstract The ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits of the VP in the control of wakefulness remain poorly understood. In the present study, we sought to elucidate the specific role of VP GABAergic neurons in controlling sleep–wake behaviors in mice. Fiber photometry revealed that the population activity of VP GABAergic neurons was increased during physiological transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep. Moreover, chemogenetic and optogenetic manipulations were leveraged to investigate a potential causal role of VP GABAergic neurons in initiating and/or maintaining arousal. In vivo optogenetic stimulation of VP GABAergic neurons innervating the ventral tegmental area (VTA) strongly promoted arousal via disinhibition of VTA dopaminergic neurons. Functional in vitro mapping revealed that VP GABAergic neurons, in principle, inhibited VTA GABAergic neurons but also inhibited VTA dopaminergic neurons. In addition, optogenetic stimulation of terminals of VP GABAergic neurons revealed that they promoted arousal by innervating the lateral hypothalamus, but not the mediodorsal thalamus or lateral habenula. The increased wakefulness chemogenetically evoked by VP GABAergic neuronal activation was completely abolished by pretreatment with dopaminergic D1 and D2/D3 receptor antagonists. Furthermore, activation of VP GABAergic neurons increased exploration time in both the open-field and light–dark box tests but did not modulate depression-like behaviors or food intake. Finally, chemogenetic inhibition of VP GABAergic neurons decreased arousal. Taken together, our findings indicate that VP GABAergic neurons are essential for arousal related to motivation.

scholarly journals 0074 Inhibitory Neurons in the Dorsomedial Medulla Promote REM Sleep

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A30-A30
Author(s):  
J Stucynski ◽  
A Schott ◽  
J Baik ◽  
J Hong ◽  
F Weber ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Nrem Sleep ◽  
Inhibitory Neurons ◽  
Brain State ◽  
Sleep Regulation ◽  
Optogenetic Stimulation ◽  
Electrophysiological Recordings ◽  
Stimulation Of

Abstract Introduction The neural circuits controlling rapid eye movement (REM) sleep, and in particular the role of the medulla in regulating this brain state, remains an active area of study. Previous electrophysiological recordings in the dorsomedial medulla (DM) and electrical stimulation experiments suggested an important role of this area in the control of REM sleep. However the identity of the involved neurons and their precise role in REM sleep regulation are still unclear. Methods The properties of DM GAD2 neurons in mice were investigated through stereotaxic injection of CRE-dependent viruses in conjunction with implantation of electrodes for electroencephalogram (EEG) and electromyogram (EMG) recordings and optic fibers. Experiments included in vivo calcium imaging (fiber photometry) across sleep and wake states, optogenetic stimulation of cell bodies, chemogenetic excitation and suppression (DREADDs), and connectivity mapping using viral tracing and optogenetics. Results Imaging the calcium activity of DM GAD2 neurons in vivo indicates that these neurons are most active during REM sleep. Optogenetic stimulation of DM GAD2 neurons reliably triggered transitions into REM sleep from NREM sleep. Consistent with this, chemogenetic activation of DM GAD2 neurons increased the amount of REM sleep while inhibition suppressed its occurrence and enhanced NREM sleep. Anatomical tracing revealed that DM GAD2 neurons project to several areas involved in sleep / wake regulation including the wake-promoting locus coeruleus (LC) and the REM sleep-suppressing ventrolateral periaquaductal gray (vlPAG). Optogenetic activation of axonal projections from DM to LC, and DM to vlPAG was sufficient to induce REM sleep. Conclusion These experiments demonstrate that DM inhibitory neurons expressing GAD2 powerfully promote initiation of REM sleep in mice. These findings further characterize the dorsomedial medulla as a critical structure involved in REM sleep regulation and inform future investigations of the REM sleep circuitry. Support R01 HL149133

scholarly journals Optogenetic Stimulation of the Corticothalamic Pathway Affects Relay Cells and GABAergic Neurons Differently in the Mouse Visual Thalamus

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e45717 ◽  
Author(s):  
Chris W. D. Jurgens ◽  
Karen A. Bell ◽  
A. Rory McQuiston ◽  
William Guido
Keyword(s):  
Gabaergic Neurons ◽  
Visual Thalamus ◽  
Optogenetic Stimulation ◽  
Stimulation Of

Central nystagmus. III. Functional correlations of mesodiencephalic nystagmogenic center

1959 ◽  
Vol 197 (2) ◽  
pp. 454-460 ◽  
Author(s):  
F. Bergmann ◽  
J. Lachmann ◽  
M. Monnier ◽  
P. Krupp
Keyword(s):  
Electrical Stimulation ◽  
Eye Movements ◽  
Vestibular Nuclei ◽  
Rabbit Brain ◽  
Vestibular Nystagmus ◽  
Posterior Commissure ◽  
Common Substrate ◽  
The Common ◽  
Stimulation Of

Transverse cuts at various levels of the rabbit brain stem have different effects on vestibular nystagmus and on central nystagmus elicited by electrical stimulation of the mesodiencephalic nystagmogenic area. While transections rostral to the sensitive region enhance both, probably by elimination of inhibitory influences from cortex or retina, transections caudal to this region, but rostral to the colliculi, abolish central nystagmus only. Transections at the level of the inferior colliculus abolish vestibular nystagmus only, while intermediate cuts may eliminate either response. When central nystagmus alone survives, its character is changed in a specific way indicating the important role of the vestibular nuclei in normal central nystagmus. These observations lead to an approximate localization of the common substrate for conjugate eye movements involved both in central and vestibular nystagmus. Longitudinal cuts through the posterior commissure provoke a temporary disconjugated nystagmus not described hitherto.

THE ROLE OF THE TESTIS IN THE RELEASE OF GONADOTROPHINS FROM THE HYPOPHYSIS

1962 ◽  
Vol 40 (2) ◽  
pp. 175-187 ◽  
Author(s):  
A. M. Taira ◽  
A. A. Tarkhan
Keyword(s):  
Leydig Cells ◽  
Interstitial Cells ◽  
Female Rats ◽  
List Type ◽  
Adult Rats ◽  
Male And Female Rats ◽  
Short Period ◽  
The One ◽  
Spermatogenic Epithelium

ABSTRACT To study the role of the spermatogenic epithelium and of the interstitial cells of Leydig in the release of the pituitary gonadotrophins, groups of normal, cryptorchid and castrated adult rats were joined parabiotically to immature male and female rats for a period of seven days. On examination of the genital organs of different recipients, it has been concluded that: In normal rats, there is no appreciable release of any gonadotrophin during the short period of parabiosis. The spermatogenic epithelium inhibits the release of FSH, while the interstitial cells liberate a hormone that inhibits the release of ICSH. Release of the gonadotrophin which causes luteinisation of the granulosa cells is not activated by cryptorchidism or castration. This gonadotrophin is different from the one responsible for stimulation of growth and functional activity of the Leydig cells. The term »LH« is better confined to the former and »ICSH« to the latter gonadotrophin. ICSH not only acts on the testis but also on the ovary and indirectly on the uterus; this action has been discussed.

066 Noradrenaline and acetylcholine inhibit sleep-promoting neurons of ventrolateral preoptic area through a local GABAergic circuit

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A27-A28
Author(s):  
Roberto De Luca ◽  
Stefano Nardone ◽  
Lin Zhu ◽  
Elda Arrigoni
Keyword(s):  
Muscarinic Receptors ◽  
Inhibitory Action ◽  
Preoptic Area ◽  
Brain Slices ◽  
Inhibitory Effect ◽  
Gabaergic Neurons ◽  
Optogenetic Stimulation ◽  
Direct Inhibitory Effect ◽  
Afferent Inputs ◽  
Stimulation Of

Abstract Introduction The ventrolateral preoptic (VLPO) nucleus is a key area involved in the initiation and maintenance of sleep. During wakefulness, sleep-promoting galanin neurons in the VLPO are directly inhibited by arousal signals including noradrenaline and acetylcholine. We have found that while these neurotransmitters directly inhibit VLPO galanin neurons, they also activate GABAergic neurons in the VLPO that do not express galanin. We propose that when activated by monoaminergic and cholinergic inputs, these local VLPO GABAergic neurons provide an additional inhibition of the VLPO galanin sleep-promoting neurons. We tested this model in brain slices in mice. Methods We studied VLPO galanin neurons in mouse brain slices using patch-clamp recordings. We recorded from fluorescently labeled VLPO galanin neurons following the injection of a cre-dependent AAV encoding for mCherry, into the VLPO of Gal-cre mice. For the optogenetic studies we expressed channelrhodopsin-2 (ChR-2) in VLPO VGAT neurons and mCherry in galanin neurons by injecting a flp-dependent and a cre-dependent AAV encoding respectively for ChR2 and mCherry into the VLPO of VGAT-flp::Gal-cre mice. We photo-stimulated local GABAergic neurons and recorded from labeled VLPO galanin neurons. Noradrenaline, carbachol and receptor antagonists were bath-applied. Results Noradrenaline and carbachol inhibited VLPO galanin neurons by alpha-2 and muscarinic receptors and these effects were maintained in the presence of tetrodotoxin (TTX) indicating, as previously proposed, a direct inhibitory effect of noradrenaline and carbachol on VLPO galanin neurons. In addition, both noradrenaline and carbachol increased the frequency of spontaneous inhibitory post-synaptic currents (sIPSCs) of VLPO galanin neurons, suggesting an additional inhibitory action on VLPO galanin neurons. Finally, optogenetic stimulation of local VLPO GABAergic neurons produced short latency, TTX-resistant, opto-evoked IPSCs in VLPO galanin neurons. Both noradrenaline and carbachol increased the amplitude of these opto-evoked IPSCs by the activation of alpha-1 and muscarinic receptors. Conclusion Our results demonstrate that noradrenaline and acetylcholine inhibit VLPO galanin neurons directly and indirectly. Both noradrenaline and acetylcholine increase GABAergic afferent inputs to VLPO galanin neurons by activating local GABAergic neurons. We propose that during wakefulness this feedforward inhibition provides additional inhibition of VLPO galanin sleep-promoting neurons. Support (if any) NS091126 and HL149630

scholarly journals Differential roles of pyramidal and fast-spiking, GABAergic neurons in the control of glioma cell proliferation

2020 ◽  
Author(s):  
Elena Tantillo ◽  
Eleonora Vannini ◽  
Chiara Cerri ◽  
Cristina Spalletti ◽  
Antonella Colistra ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Pyramidal Neurons ◽  
Visual Stimulation ◽  
Afferent Input ◽  
Gabaergic Neurons ◽  
Optogenetic Stimulation ◽  
Glioma Cell Proliferation ◽  
Fast Spiking ◽  
Stimulation Of

AbstractRecent studies have demonstrated an active role for neurons in glioma progression. Specifically, peritumoral neurons establish functional excitatory synapses with glioma cells, and optogenetic stimulation of cortical pyramidal neurons drives tumor progression. However, the specific role of different subsets of cortical neurons, such as GABAergic interneurons, remains unexplored. Here, we directly compared the effects of optogenetic stimulation of pyramidal cells vs. fast-spiking, GABAergic neurons. In mice inoculated with GL261 cells into the motor cortex, we show that optogenetic stimulation of pyramidal neurons enhances glioma cell proliferation. In contrast, optogenetic stimulation of fast-spiking, parvalbumin-positive interneurons reduces proliferation as measured by BrdU incorporation and Ki67 immunolabelling. Since both principal cells and fast-spiking interneurons are directly activated by sensory afferent input, we next placed tumors in the occipital cortex to test the impact of visual stimulation/deprivation. We report that total lack of visual input via dark rearing enhances the density of proliferating glioma cells, while daily visual stimulation by gratings of different spatial frequencies and contrast reduces tumor growth. The effects of sensory input are region-specific, as visual deprivation has no significant effect on tumor proliferation in mice with gliomas in the motor cortex. We also report that sensory stimulation combined with temozolomide administration delays the loss of visual responses in peritumoral neurons. Altogether, these data demonstrate complex effects of different neuronal subtypes in the control of glioma proliferation.HighlightsActivity of GABAergic neurons reduces glioma cell proliferationLevels of sensory afferent input regulate tumor proliferationEffects of sensory input are region-specific

scholarly journals Optogenetic Stimulation of GABAergic Neurons in the Globus Pallidus Produces Hyperkinesia

2018 ◽  
Vol 12 ◽  
Author(s):  
Jun Tian ◽  
Yaping Yan ◽  
Wang Xi ◽  
Rui Zhou ◽  
Huifang Lou ◽  
...  
Keyword(s):  
Globus Pallidus ◽  
Gabaergic Neurons ◽  
Optogenetic Stimulation ◽  
Stimulation Of

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

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