Optogenetic Stimulation of Neurons in the Brainstem of Freely Behaving Rats and Mice

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.

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

Frontiers in Neural Circuits ◽

10.3389/fncir.2021.639900 ◽

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.

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

10.1101/2020.11.30.404525 ◽

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

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Faculty Opinions recommendation of Optogenetic stimulation of a hippocampal engram activates fear memory recall.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.14256961.15779281 ◽

2012 ◽

Author(s):

Ted Abel ◽

Robbert Havekes

Keyword(s):

Fear Memory ◽

Memory Recall ◽

Optogenetic Stimulation ◽

Stimulation Of

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Faculty Opinions recommendation of Wireless Optogenetic Stimulation of Oxytocin Neurons in a Semi-natural Setup Dynamically Elevates Both Pro-social and Agonistic Behaviors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738143860.793576394 ◽

2020 ◽

Author(s):

Gerd Kempermann

Keyword(s):

Optogenetic Stimulation ◽

Stimulation Of

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Incerto-thalamic modulation of fear via GABA and dopamine

Neuropsychopharmacology ◽

10.1038/s41386-021-01006-5 ◽

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.

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

Scientific Reports ◽

10.1038/s41598-021-82773-5 ◽

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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Direct optogenetic stimulation of smooth muscle cells to control gastric contractility

10.1055/s-0041-1733752 ◽

2021 ◽

Author(s):

R Patejdl ◽

M Vogt ◽

B Schulz ◽

A Wagdi ◽

J Lebert ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Muscle Cells ◽

Optogenetic Stimulation ◽

Stimulation Of

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Striatal dopamine mediates hallucination-like perception in mice

Science ◽

10.1126/science.abf4740 ◽

2021 ◽

Vol 372 (6537) ◽

pp. eabf4740

Author(s):

K. Schmack ◽

M. Bosc ◽

T. Ott ◽

J. F. Sturgill ◽

A. Kepecs

Keyword(s):

Psychotic Disorders ◽

Neural Circuit ◽

Dopamine Neurons ◽

Striatal Dopamine ◽

Model Organisms ◽

High Confidence ◽

Optogenetic Stimulation ◽

The Brain ◽

Central Symptom ◽

Stimulation Of

Hallucinations, a central symptom of psychotic disorders, are attributed to excessive dopamine in the brain. However, the neural circuit mechanisms by which dopamine produces hallucinations remain elusive, largely because hallucinations have been challenging to study in model organisms. We developed a task to quantify hallucination-like perception in mice. Hallucination-like percepts, defined as high-confidence false detections, increased after hallucination-related manipulations in mice and correlated with self-reported hallucinations in humans. Hallucination-like percepts were preceded by elevated striatal dopamine levels, could be induced by optogenetic stimulation of mesostriatal dopamine neurons, and could be reversed by the antipsychotic drug haloperidol. These findings reveal a causal role for dopamine-dependent striatal circuits in hallucination-like perception and open new avenues to develop circuit-based treatments for psychotic disorders.

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