scholarly journals Freely behaving mice can brake and turn during optogenetic stimulation of the Mesencephalic Locomotor Region

2020 ◽  
Author(s):  
Cornelis Immanuel van der Zouwen ◽  
Joël Boutin ◽  
Maxime Fougère ◽  
Aurélie Flaive ◽  
Mélanie Vivancos ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Environmental Cues ◽  
List Type ◽  
Dependent Manner ◽  
Turn Angle ◽  
Mesencephalic Locomotor Region ◽  
Optogenetic Stimulation ◽  
Limb Kinematics ◽  
Freely Behaving ◽  
Stimulation Of

AbstractBackgroundStimulation of the Mesencephalic Locomotor Region (MLR) is increasingly considered as a target to improve locomotor function in Parkinson’s disease, spinal cord injury and stroke. A key function of the MLR is to control the speed of forward symmetrical locomotor movements. However, the ability of freely moving mammals to integrate environmental cues to brake and turn during MLR stimulation is poorly documented.Objective/hypothesisWe investigated whether freely behaving mice could brake or turn based on environmental cues during MLR stimulation.MethodsWe stimulated the cuneiform nucleus in mice expressing channelrhodopsin in Vglut2-positive neurons in a Cre-dependent manner (Vglut2-ChR2-EYFP) using optogenetics. We detected locomotor movements using deep learning. We used patch-clamp recordings to validate the functional expression of channelrhodopsin and neuroanatomy to visualize the stimulation sites.ResultsOptogenetic stimulation of the MLR evoked locomotion and increasing laser power increased locomotor speed. Gait diagram and limb kinematics were similar during spontaneous and optogenetic-evoked locomotion. Mice could brake and make sharp turns (∼90⁰) when approaching a corner during MLR stimulation in an open-field arena. The speed during the turn was scaled with the speed before the turn, and with the turn angle. In a reporter mouse, many Vglut2-ZsGreen neurons were immunopositive for glutamate in the MLR. Patch-clamp recordings in Vglut2-ChR2-EYFP mice show that blue light evoked short latency spiking in MLR neurons.ConclusionMLR glutamatergic neurons are a relevant target to improve locomotor activity without impeding the ability to brake and turn when approaching an obstacle, thus ensuring smooth and adaptable navigation.Highlights-Mice brake and turn when approaching the arena’s corner during MLR-evoked locomotion-Speed decrease is scaled to speed before the turn during MLR-evoked locomotion-Turn angle is scaled to turn speed during MLR-evoked locomotion-Gait and limb kinematics are similar during spontaneous and MLR-evoked locomotion

scholarly journals Freely Behaving Mice Can Brake and Turn During Optogenetic Stimulation of the Mesencephalic Locomotor Region

2021 ◽  
Vol 15 ◽  
Author(s):  
Cornelis Immanuel van der Zouwen ◽  
Joël Boutin ◽  
Maxime Fougère ◽  
Aurélie Flaive ◽  
Mélanie Vivancos ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Open Field ◽  
Environmental Cues ◽  
Dependent Manner ◽  
Mesencephalic Locomotor Region ◽  
Optogenetic Stimulation ◽  
Cuneiform Nucleus ◽  
Cord Injury ◽  
Freely Behaving ◽  
Stimulation Of

A key function of the mesencephalic locomotor region (MLR) is to control the speed of forward symmetrical locomotor movements. However, the ability of freely moving mammals to integrate environmental cues to brake and turn during MLR stimulation is poorly documented. Here, we investigated whether freely behaving mice could brake or turn, based on environmental cues during MLR stimulation. We photostimulated the cuneiform nucleus (part of the MLR) in mice expressing channelrhodopsin in Vglut2-positive neurons in a Cre-dependent manner (Vglut2-ChR2-EYFP) using optogenetics. We detected locomotor movements using deep learning. We used patch-clamp recordings to validate the functional expression of channelrhodopsin and neuroanatomy to visualize the stimulation sites. In the linear corridor, gait diagram and limb kinematics were similar during spontaneous and optogenetic-evoked locomotion. In the open-field arena, optogenetic stimulation of the MLR evoked locomotion, and increasing laser power increased locomotor speed. Mice could brake and make sharp turns (~90°) when approaching a corner during MLR stimulation in the open-field arena. The speed during the turn was scaled with the speed before the turn, and with the turn angle. Patch-clamp recordings in Vglut2-ChR2-EYFP mice show that blue light evoked short-latency spiking in MLR neurons. Our results strengthen the idea that different brainstem neurons convey braking/turning and MLR speed commands in mammals. Our study also shows that Vglut2-positive neurons of the cuneiform nucleus are a relevant target to increase locomotor activity without impeding the ability to brake and turn when approaching obstacles, thus ensuring smooth and adaptable navigation. Our observations may have clinical relevance since cuneiform nucleus stimulation is increasingly considered to improve locomotion function in pathological states such as Parkinson’s disease, spinal cord injury, or stroke.

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 Scanned optogenetic control of mammalian somatosensory input to map input-specific behavioral outputs

2020 ◽  
Author(s):  
Ara Schorscher-Petcu ◽  
Flóra Takács ◽  
Liam E. Browne
Keyword(s):  
Action Potential ◽  
Stimulus Intensity ◽  
Behavioral Responses ◽  
Behavioral Measures ◽  
Optogenetic Stimulation ◽  
Somatosensory Input ◽  
Sensory Motor ◽  
Freely Behaving ◽  
Somatosensory Stimuli ◽  
Stimulation Of

AbstractSomatosensory stimuli guide and shape behavior, from immediate protective reflexes to longer-term learning and high-order processes related to pain and touch. However, somatosensory inputs are challenging to control in awake mammals due to the diversity and nature of contact stimuli. Application of cutaneous stimuli is currently limited to relatively imprecise methods as well as subjective behavioral measures. The strategy we present here overcomes these difficulties by achieving spatiotemporally precise, remote and dynamic optogenetic stimulation of skin by projecting light to a small defined area in freely-behaving mice. We mapped behavioral responses to specific nociceptive inputs and revealed a sparse code for stimulus intensity: using the first action potential, the number of activated nociceptors governs the timing and magnitude of rapid protective pain-related behavior. The strategy can be used to define specific behavioral repertoires, examine the timing and nature of reflexes, and dissect sensory, motor, cognitive and motivational processes guiding behavior.

scholarly journals A peptidergic amygdala microcircuit modulates sexually dimorphic contextual fear

2020 ◽  
Author(s):  
AK Rajbhandari ◽  
JC Octeau ◽  
S Gonzalez ◽  
ZT Pennington ◽  
J Trott ◽  
...  
Keyword(s):  
Fear Extinction ◽  
Sexually Dimorphic ◽  
Dependent Manner ◽  
Post Traumatic Stress ◽  
Pac1 Receptor ◽  
Contextual Fear ◽  
Optogenetic Stimulation ◽  
Post Traumatic ◽  
Stimulation Of

AbstractTrauma can cause dysfunctional fear regulation leading some to develop disorders like post-traumatic stress disorder (PTSD). The amygdala regulates fear, and, PACAP and PAC1 receptors are linked to PTSD symptom severity at genetic/epigenetic levels, with a strong link in females with PTSD. We discovered a PACAPergic projection from the basomedial amygdala (BMA) to the medial intercalated cells (mICCs). In vivo optogenetic stimulation of this pathway increased cfos expression in mICCs, decreased fear retention and increased fear extinction. Selective deletion of PAC1 receptors from the mICCs in females reduced fear acquisition, but enhanced fear generalization and reduced fear extinction in males. Optogenetic stimulation of the BMA-mICCs PACAPergic pathway produced excitatory postsynaptic currents (EPSCs) in mICCs neurons, which was enhanced by PAC1 receptor antagonist, PACAP 6-38. Our findings show that mICCs modulate contextual fear in a dynamic and sex-dependent manner via the microcircuit containing the BMA and mICCs, dependent on behavioral state.

scholarly journals Optogenetic stimulation of long-range inputs and functional characterization of connectivity in patch-clamp recordings in mouse brain slices

2018 ◽  
Author(s):  
Louis Richevaux ◽  
Louise Schenberg ◽  
Mathieu Beraneck ◽  
Desdemona Fricker
Keyword(s):  
Patch Clamp ◽  
Long Range ◽  
Brain Slices ◽  
Cell Type ◽  
Patch Clamp Recording ◽  
Axon Terminals ◽  
Optogenetic Stimulation ◽  
Cell Type Specific ◽  
The Brain ◽  
Stimulation Of

Knowledge of cell type specific synaptic connectivity is a crucial prerequisite for understanding brain wide neuronal circuits. The functional investigation of long-range connections requires targeted recordings of single neurons combined with the specific stimulation of identified distant inputs. This is often difficult to achieve with conventional, electrical stimulation techniques, because axons from converging upstream brain areas may intermingle in the target region. The stereotaxic targeting of a specific brain region for virus-mediated expression of light sensitive ion channels allows to selectively stimulate axons coming from that region with light. Intracerebral stereotaxic injections can be used in well-delimited structures, such as the anterodorsal thalamic nuclei, and also in other subcortical or cortical areas throughout the brain. Here we describe a set of techniques for precise stereotaxic injection of viral vectors expressing channelrhodopsin in the anterodorsal thalamus, followed by photostimulation of their axon terminals in hippocampal slices. In combination with whole-cell patch clamp recording from a postsynaptically connected presubicular neuron, photostimulation of thalamic axons allows the detection of functional synaptic connections, their pharmacological characterization, and the evaluation of their strength in the brain slice preparation. We demonstrate that axons originating in the anterodorsal thalamus ramify densely in presubicular layers 1 and 3. The photostimulation of Chronos expressing thalamic axon terminals in presubiculum initiates short latency postsynaptic responses in a presubicular layer3 neuron, indicating a monosynaptic connection. In addition, biocytin filling of the recorded neuron and posthoc revelation confirms the layer localization and pyramidal morphology of the postsynaptic neuron. Taken together, the optogenetic stimulation of long-range inputs in ex vivo brain slices is a useful method to determine the cell-type specific functional connectivity from distant brain regions.

scholarly journals A pretectal command system controls hunting behaviour

2019 ◽  
Author(s):  
Paride Antinucci ◽  
Mónica Folgueira ◽  
Isaac H. Bianco
Keyword(s):  
Calcium Imaging ◽  
List Type ◽  
Specific Population ◽  
Predatory Behaviour ◽  
Larval Zebrafish ◽  
Optogenetic Stimulation ◽  
Hunting Behaviour ◽  
Action Sequences ◽  
Innate Behaviour ◽  
Stimulation Of

AbstractFor many species, hunting is an innate behaviour that is crucial for survival, yet the circuits that control predatory action sequences are poorly understood. We used larval zebrafish to identify a command system that controls hunting. By combining calcium imaging with a virtual hunting assay, we identified a discrete pretectal region that is selectively active when animals initiate hunting. Targeted genetic labelling allowed us to examine the function and morphology of individual cells and identify two classes of pretectal neuron that project to ipsilateral optic tectum or the contralateral tegmentum. Optogenetic stimulation of single neurons of either class was able to induce sustained hunting sequences, in the absence of prey. Furthermore, laser ablation of these neurons impaired prey-catching and prevented induction of hunting by optogenetic stimulation of the anterior-ventral tectum. In sum, we define a specific population of pretectal neurons that functions as a command system to drive predatory behaviour.Key findingsPretectal neurons are recruited during hunting initiationOptogenetic stimulation of single pretectal neurons can induce predatory behaviourAblation of pretectal neurons impairs huntingPretectal cells comprise a command system controlling hunting behaviour

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 Amygdala controls saccade and gaze physically, motivationally, and socially

2019 ◽  
Author(s):  
Kazutaka Maeda ◽  
Ken-ichi Inoue ◽  
Jun Kunimatsu ◽  
Masahiko Takada ◽  
Okihide Hikosaka
Keyword(s):  
Social Interaction ◽  
Contralateral Side ◽  
Central Nucleus ◽  
List Type ◽  
Optogenetic Stimulation ◽  
Control Behavior ◽  
Emotional Events ◽  
Goal Directed Behavior ◽  
New Framework ◽  
Stimulation Of

AbstractThe amygdala is uniquely sensitive to emotional events. However, it is not understood whether and how the amygdala uses such emotional signals to control behavior, especially eye movements. We therefore injected muscimol (GABAAagonist) into the central nucleus of amygdala (CeA) in monkeys. This unilateral temporary inactivation suppressed saccades to contralateral but not ipsilateral targets, resulting in longer latencies, hypometric amplitudes, and slower velocity. During free viewing of movies, gaze was distributed mostly in the ipsilateral hemifield. Moreover, CeA inactivation disrupted the tendency of gaze toward social interaction images, which were normally focused on continuously. Conversely, optogenetic stimulation of CeA facilitated saccades to the contralateral side. These findings suggest that CeA controls spatially selective gaze and attention in emotional contexts, and provide a new framework for understanding psychiatric disorders related to amygdala dysfunction.HighlightsCentral amygdala facilitates contralateral saccades selectively.Saccade facilitation is related to motivational goals and social interaction.The amygdala thus controls goal-directed behavior based on emotional contexts.

DER EINFLUSS VON RESERPIN AUF DIE ANTITHYREOIDALE WIRKUNG VON KALIUMPERCHLORAT

1962 ◽  
Vol 39 (3) ◽  
pp. 423-430
Author(s):  
H. L. Krüskemper ◽  
F. J. Kessler ◽  
E. Steinkrüger
Keyword(s):  
Thyroid Gland ◽  
Male Rats ◽  
Normal Male ◽  
Tissue Respiration ◽  
List Type ◽  
Morphological Alterations ◽  
Hormone Synthesis ◽  
Stimulation Of

ABSTRACT 1. Reserpine does not inhibit the tissue respiration of liver in normal male rats (in vitro). 2. The decrease of tissue respiration of the liver with simultaneous morphological stimulation of the thyroid gland after long administration of reserpine is due to a minute inhibition of the hormone synthesis in the thyroid gland. 3. The morphological alterations of the thyroid in experimental hypothyroidism due to perchlorate can not be prevented with reserpine.

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