scholarly journals 0154 Role of Noradrenergic Projection to the Preoptic Area in Regulation of Arousal

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A61-A61
Author(s):  
H Antila ◽  
I Kwak ◽  
I Covarrubias ◽  
J Baik ◽  
J Hong ◽  
...  
Keyword(s):  
Preoptic Area ◽  
Brain Regions ◽  
Brain State ◽  
Research Fellowship ◽  
Optogenetic Stimulation ◽  
Long Time ◽  
Brain States ◽  
Stimulation Of

Abstract Introduction Locus coeruleus (LC) is a noradrenergic nucleus in the brainstem involved in the regulation of attention, arousal, mood and sensory gating. LC projects to multiple brain regions and recent development of novel systems neuroscience tools allows the dissection of projection-specific LC function in more detail. One of the regions with noradrenergic projection is the preoptic area of the hypothalamus (POA). POA has been shown to contain neurons that are important for regulating sleep, and we have examined the function of the LC projection to the POA in sleep and arousal. Methods We used optogenetics, chemogenetics, fiber photometry and in vivo electrophysiology to study the function of LC noradrenergic projection to the POA. Results Norepinephrine release in the POA fluctuates with brain state changes indicating that the LC to POA projection may be involved in regulating sleep and arousal. Optogenetic stimulation of LC fibers in the POA promotes wakefulness. Furthermore, optogenetic stimulation of the LC fibers in the POA modulates the activity of sleep- and wake-active neurons. Conclusion We have identified the role of the LC noradrenergic projection to the POA in the regulation of brain states. Stimulation of the LC fibers in the POA promotes wakefulness and modulates the activity dynamics of sleep- and wake-active neurons in the POA. Our results provide more detailed information about the role of this specific projection, which has been known to exist for a long time, but with insufficient in vivo evidence of its precise function. Support Sigrid Juselius foundation, Alfred P. Sloan Research Fellowship in Neuroscience, The Whitehall foundation grant, McCabe Fund Award, NARSAD Young Investigator Award.

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 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 In Vivo Optogenetic Stimulation of Neocortical Excitatory Neurons Drives Brain-State-Dependent Inhibition

2011 ◽  
Vol 21 (19) ◽  
pp. 1593-1602 ◽  
Author(s):  
Celine Mateo ◽  
Michael Avermann ◽  
Luc J. Gentet ◽  
Feng Zhang ◽  
Karl Deisseroth ◽  
...  
Keyword(s):  
Brain State ◽  
Optogenetic Stimulation ◽  
State Dependent ◽  
Excitatory Neurons ◽  
Dependent Inhibition ◽  
Stimulation Of

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 Opposing Influence of Sensory and Motor Cortical Input on Striatal Circuitry and Choice Behavior

2018 ◽  
Author(s):  
Christian R. Lee ◽  
Alex J. Yonk ◽  
Joost Wiskerke ◽  
Kenneth G. Paradiso ◽  
James M. Tepper ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Dorsal Striatum ◽  
Behavioral Effect ◽  
Projection Neurons ◽  
Cortical Input ◽  
Optogenetic Stimulation ◽  
Main Input ◽  
Opposing Effects ◽  
Stimulation Of

SummaryThe striatum is the main input nucleus of the basal ganglia and is a key site of sensorimotor integration. While the striatum receives extensive excitatory afferents from the cerebral cortex, the influence of different cortical areas on striatal circuitry and behavior is unknown. Here we find that corticostriatal inputs from whisker-related primary somatosensory (S1) and motor (M1) cortex differentially innervate projection neurons and interneurons in the dorsal striatum, and exert opposing effects on sensory-guided behavior. Optogenetic stimulation of S1-corticostriatal afferents in ex vivo recordings produced larger postsynaptic potentials in striatal parvalbumin (PV)-expressing interneurons than D1- or D2-expressing spiny projection neurons (SPNs), an effect not observed for M1-corticostriatal afferents. Critically, in vivo optogenetic stimulation of S1-corticostriatal afferents produced task-specific behavioral inhibition, which was bidirectionally modulated by striatal PV interneurons. Optogenetic stimulation of M1 afferents produced the opposite behavioral effect. Thus, our results suggest opposing roles for sensory and motor cortex in behavioral choice via distinct influences on striatal circuitry.

scholarly journals Optogenetic spatial and temporal control of cortical circuits on a columnar scale

2016 ◽  
Vol 115 (2) ◽  
pp. 1043-1062 ◽  
Author(s):  
Arani Roy ◽  
Jason J. Osik ◽  
Neil J. Ritter ◽  
Shen Wang ◽  
James T. Shaw ◽  
...  
Keyword(s):  
Visual Stimulation ◽  
Liquid Crystal Display ◽  
Brain Regions ◽  
Cortical Activation ◽  
Mammalian Brain ◽  
Optogenetic Stimulation ◽  
Brain Surface ◽  
Stimulation System ◽  
Circuit Function ◽  
Stimulation Of

Many circuits in the mammalian brain are organized in a topographic or columnar manner. These circuits could be activated—in ways that reveal circuit function or restore function after disease—by an artificial stimulation system that is capable of independently driving local groups of neurons. Here we present a simple custom microscope called ProjectorScope 1 that incorporates off-the-shelf parts and a liquid crystal display (LCD) projector to stimulate surface brain regions that express channelrhodopsin-2 (ChR2). In principle, local optogenetic stimulation of the brain surface with optical projection systems might not produce local activation of a highly interconnected network like the cortex, because of potential stimulation of axons of passage or extended dendritic trees. However, here we demonstrate that the combination of virally mediated ChR2 expression levels and the light intensity of ProjectorScope 1 is capable of producing local spatial activation with a resolution of ∼200–300 μm. We use the system to examine the role of cortical activity in the experience-dependent emergence of motion selectivity in immature ferret visual cortex. We find that optogenetic cortical activation alone—without visual stimulation—is sufficient to produce increases in motion selectivity, suggesting the presence of a sharpening mechanism that does not require precise spatiotemporal activation of the visual system. These results demonstrate that optogenetic stimulation can sculpt the developing brain.

Possible role of cyclic GMP in stimulus-secretion coupling by salt gland of the duck

1979 ◽  
Vol 237 (5) ◽  
pp. C200-C204 ◽  
Author(s):  
D. J. Stewart ◽  
J. Sax ◽  
R. Funk ◽  
A. K. Sen
Keyword(s):  
Cyclic Amp ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Salt Gland ◽  
Domestic Ducks ◽  
Stimulus Secretion Coupling ◽  
Stimulation Of

Stimulation of salt galnd secretion in domestic ducks in vivo increased the cyclic GMP concentration of the tissue, but had no effect on cyclic AMP levels. Methacholine, which is known to stimulate sodium transport by the glands both in vivo and in vitro, stimulated ouabain-sensitive respiration in salt gland slices. Cyclic GMP stimulated ouabain-sensitive respiration to the same extent as methacholine. Guanylate cyclase stimulators, hydroxylamine and sodium azide, also stimulated ouabain-sensitive respiration. The stimulation of ouabain-sensitive respiration by methacholine was blocked either by atropine or by removal of calcium from the incubation medium. The stimulation of ouabain-sensitive respiration by cyclic GMP still occurred in the absence of calcium. The above observations seem to indicate that cyclic GMP acts as a tertiary link in the process of stimulus-secretion coupling in the tissue.

Role of adrenal catecholamines in cerebrovasodilation evoked from brain stem

1987 ◽  
Vol 252 (6) ◽  
pp. H1183-H1191
Author(s):  
C. Iadecola ◽  
P. M. Lacombe ◽  
M. D. Underwood ◽  
T. Ishitsuka ◽  
D. J. Reis
Keyword(s):  
Brain Function ◽  
Blood Gases ◽  
Brain Regions ◽  
Elevated Plasma ◽  
Regional Cerebral Blood ◽  
Medullary Reticular Formation ◽  
Alpha Chloralose ◽  
The Brain ◽  
Stimulation Of

We studied whether adrenal medullary catecholamines (CAs) contribute to the metabolically linked increase in regional cerebral blood flow (rCBF) elicited by electrical stimulation of the dorsal medullary reticular formation (DMRF). Rats were anesthetized (alpha-chloralose, 30 mg/kg), paralyzed, and artificially ventilated. The DMRF was electrically stimulated with intermittent trains of pulses through microelectrodes stereotaxically implanted. Blood gases were controlled and, during stimulation, arterial pressure was maintained within the autoregulated range for rCBF. rCBF and blood-brain barrier (BBB) permeability were determined in homogenates of brain regions by using [14C]iodoantipyrine and alpha-aminoisobutyric acid (AIB), respectively, as tracers. Plasma CAs (epinephrine and norepinephrine) were measured radioenzymatically. DMRF stimulation increased rCBF throughout the brain (n = 5; P less than 0.01, analysis of variance) and elevated plasma CAs substantially (n = 4). Acute bilateral adrenalectomy abolished the increase in plasma epinephrine (n = 4), reduced the increases in flow (n = 6) in cerebral cortex (P less than 0.05), and abolished them elsewhere in brain (P greater than 0.05). Comparable effects on rCBF were obtained by selective adrenal demedullation (n = 7) or pretreatment with propranolol (1.5 mg/kg iv) (n = 5). DMRF stimulation did not increase the permeability of the BBB to AIB (n = 5). We conclude that the increases in rCBF elicited from the DMRF has two components, one dependent on, and the other independent of CAs. Since the BBB is impermeable to CAs and DMRF stimulation fails to open the BBB, the results suggest that DMRF stimulation allows, through a mechanism not yet determined, circulating CAs to act on brain and affect brain function.

scholarly journals Parylene photonics: a flexible, broadband optical waveguide platform with integrated micromirrors for biointerfaces

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Jay W. Reddy ◽  
Maya Lassiter ◽  
Maysamreza Chamanzar
Keyword(s):  
Optical Waveguides ◽  
Brain Activity ◽  
Low Loss ◽  
Parylene C ◽  
Optogenetic Stimulation ◽  
Patterned Illumination ◽  
The Brain ◽  
532 Nm ◽  
Stimulation Of

Abstract Targeted light delivery into biological tissue is needed in applications such as optogenetic stimulation of the brain and in vivo functional or structural imaging of tissue. These applications require very compact, soft, and flexible implants that minimize damage to the tissue. Here, we demonstrate a novel implantable photonic platform based on a high-density, flexible array of ultracompact (30 μm × 5 μm), low-loss (3.2 dB/cm at λ = 680 nm, 4.1 dB/cm at λ = 633 nm, 4.9 dB/cm at λ = 532 nm, 6.1 dB/cm at λ = 450 nm) optical waveguides composed of biocompatible polymers Parylene C and polydimethylsiloxane (PDMS). This photonic platform features unique embedded input/output micromirrors that redirect light from the waveguides perpendicularly to the surface of the array for localized, patterned illumination in tissue. This architecture enables the design of a fully flexible, compact integrated photonic system for applications such as in vivo chronic optogenetic stimulation of brain activity.

scholarly journals Pedunculopontine glutamatergic neurons control spike patterning in substantia nigra dopaminergic neurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Daniel J Galtieri ◽  
Chad M Estep ◽  
David L Wokosin ◽  
Stephen Traynelis ◽  
D James Surmeier
Keyword(s):  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Glutamatergic Synapses ◽  
Glutamatergic Neurons ◽  
Oscillatory Mechanisms ◽  
Goal Directed Behavior ◽  
Stimulation Of

Burst spiking in substantia nigra pars compacta (SNc) dopaminergic neurons is a key signaling event in the circuitry controlling goal-directed behavior. It is widely believed that this spiking mode depends upon an interaction between synaptic activation of N-methyl-D-aspartate receptors (NMDARs) and intrinsic oscillatory mechanisms. However, the role of specific neural networks in burst generation has not been defined. To begin filling this gap, SNc glutamatergic synapses arising from pedunculopotine nucleus (PPN) neurons were characterized using optical and electrophysiological approaches. These synapses were localized exclusively on the soma and proximal dendrites, placing them in a good location to influence spike generation. Indeed, optogenetic stimulation of PPN axons reliably evoked spiking in SNc dopaminergic neurons. Moreover, burst stimulation of PPN axons was faithfully followed, even in the presence of NMDAR antagonists. Thus, PPN-evoked burst spiking of SNc dopaminergic neurons in vivo may not only be extrinsically triggered, but extrinsically patterned as well.

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