Optogenetic Stimulation of C1 and Retrotrapezoid Nucleus Neurons Causes Sleep State–Dependent Cardiorespiratory Stimulation and Arousal in Rats

Combined optogenetic activation of the retrotrapezoid nucleus (RTN; a CO2/proton-activated brainstem nucleus) with nearby catecholaminergic neurons (C1 and A5), or selective C1 neuron stimulation, increases blood pressure (BP) and breathing, causes arousal from non-rapid eye movement (non-REM) sleep, and triggers sighs. Here we wished to determine which of these physiological responses are elicited when RTN neurons are selectively activated. The left rostral RTN and nearby A5 neurons were transduced with channelrhodopsin-2 (ChR2+) using a lentiviral vector. Very few C1 cells were transduced. BP, breathing, EEG, and neck EMG were monitored. During non-REM sleep, photostimulation of ChR2+ neurons (20s, 2-20 Hz) instantly increased V̇e without changing BP (13 rats). V̇e and BP were unaffected by light in nine control (ChR2−) rats. Photostimulation produced no sighs and caused arousal (EEG desynchronization) more frequently in ChR2+ than ChR2− rats (62 ± 5% of trials vs. 25 ± 2%; P < 0.0001). Six ChR2+ rats then received spinal injections of a saporin-based toxin that spared RTN neurons but destroyed surrounding catecholaminergic neurons. Photostimulation of the ChR2+ neurons produced the same ventilatory stimulation before and after lesion, but arousal was no longer elicited. Overall (all ChR2+ rats combined), ΔV̇e correlated with the number of ChR2+ RTN neurons whereas arousal probability correlated with the number of ChR2+ catecholaminergic neurons. In conclusion, RTN neurons activate breathing powerfully and, unlike the C1 cells, have minimal effects on BP and have a weak arousal capability at best. A5 neuron stimulation produces little effect on breathing and BP but does appear to facilitate arousal.

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Faculty Opinions recommendation of Selective optogenetic stimulation of the retrotrapezoid nucleus in sleeping rats activates breathing without changing blood pressure or causing arousal or sighs.

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

10.3410/f.725430308.793505831 ◽

2015 ◽

Author(s):

James Duffin

Keyword(s):

Blood Pressure ◽

Optogenetic Stimulation ◽

Retrotrapezoid Nucleus ◽

Stimulation Of

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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 State-dependent control of breathing by the retrotrapezoid nucleus.

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

10.3410/f.725410481.793526842 ◽

2017 ◽

Author(s):

Mathias Dutschmann

Keyword(s):

Control Of Breathing ◽

Retrotrapezoid Nucleus ◽

State Dependent

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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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