scholarly journals Chemogenetic modulation of histaminergic neurons in the tuberomammillary nucleus alters territorial aggression and wakefulness

2021 ◽  
Author(s):  
Fumito Naganuma ◽  
Tadaho Nakamura ◽  
Hiroshi Kuroyanagi ◽  
Masato Tanaka ◽  
Takeo Yoshikawa ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Nrem Sleep ◽  
Cre Recombinase ◽  
Designer Drugs ◽  
Brain Histamine ◽  
Tuberomammillary Nucleus ◽  
Territorial Aggression ◽  
Neuronal Populations ◽  
Histaminergic Neurons ◽  
Aggressive Behaviours

Abstract Designer receptor activated by designer drugs (DREADDs) techniques are widely used to modulate the activities of specific neuronal populations during behavioural tasks. However, DREADDs-induced modulation of histaminergic neurons in the tuberomammillary nucleus (HATMN neurons) has produced inconsistent effects on the sleep–wake cycle, possibly due to the use of Hdc-Cre mice driving Cre recombinase and DREADDs activity outside the targeted region. Moreover, previous DREADDs studies have not examined locomotor activity and aggressive behaviours, which are also regulated by brain histamine levels. In the present study, we investigated the effects of HATMN activation and inhibition on the locomotor activity, aggressive behaviours and sleep–wake cycle of Hdc-Cre mice with minimal non-target expression of Cre-recombinase. Chemoactivation of HATMN moderately enhanced locomotor activity in a novel open field. Activation of HATMN neurons significantly enhanced aggressive behaviour in the resident–intruder test. Wakefulness was increased and non-rapid eye movement (NREM) sleep decreased for an hour by HATMN chemoactivation. Conversely HATMN chemoinhibition decreased wakefulness and increased NREM sleep for 6 hours. These changes in wakefulness induced by HATMN modulation were related to vigilance status transition. These results indicate the influences of HATMN neurons on exploratory activity, territorial aggression, and wake maintenance.

scholarly journals Chemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fumito Naganuma ◽  
Tadaho Nakamura ◽  
Hiroshi Kuroyanagi ◽  
Masato Tanaka ◽  
Takeo Yoshikawa ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Nrem Sleep ◽  
Cre Recombinase ◽  
Designer Drugs ◽  
Brain Histamine ◽  
Territorial Aggression ◽  
Neuronal Populations ◽  
Histaminergic Neurons ◽  
Tuberomamillary Nucleus ◽  
Aggressive Behaviours

AbstractDesigner receptor activated by designer drugs (DREADDs) techniques are widely used to modulate the activities of specific neuronal populations during behavioural tasks. However, DREADDs-induced modulation of histaminergic neurons in the tuberomamillary nucleus (HATMN neurons) has produced inconsistent effects on the sleep–wake cycle, possibly due to the use of Hdc-Cre mice driving Cre recombinase and DREADDs activity outside the targeted region. Moreover, previous DREADDs studies have not examined locomotor activity and aggressive behaviours, which are also regulated by brain histamine levels. In the present study, we investigated the effects of HATMN activation and inhibition on the locomotor activity, aggressive behaviours and sleep–wake cycle of Hdc-Cre mice with minimal non-target expression of Cre-recombinase. Chemoactivation of HATMN moderately enhanced locomotor activity in a novel open field. Activation of HATMN neurons significantly enhanced aggressive behaviour in the resident–intruder test. Wakefulness was increased and non-rapid eye movement (NREM) sleep decreased for an hour by HATMN chemoactivation. Conversely HATMN chemoinhibition decreased wakefulness and increased NREM sleep for 6 h. These changes in wakefulness induced by HATMN modulation were related to the maintenance of vigilance state. These results indicate the influences of HATMN neurons on exploratory activity, territorial aggression, and wake maintenance.

scholarly journals The Interaction Between the Ventrolateral Preoptic Nucleus and the Tuberomammillary Nucleus in Regulating the Sleep-Wakefulness Cycle

2020 ◽  
Vol 14 ◽  
Author(s):  
Juan Cheng ◽  
Fang Wu ◽  
Mingrui Zhang ◽  
Ding Ding ◽  
Sumei Fan ◽  
...  
Keyword(s):  
Nrem Sleep ◽  
Sleep Time ◽  
Preoptic Nucleus ◽  
Flip Flop ◽  
Excitatory Neurotransmitter ◽  
Tuberomammillary Nucleus ◽  
Histaminergic Neurons ◽  
Electrode Recording ◽  
The Central Nervous System ◽  
Ventrolateral Preoptic Nucleus

The ventrolateral preoptic nucleus (VLPO) in the anterior hypothalamus and the tuberomammillary nucleus (TMN) in the posterior hypothalamus are critical regions which involve the regulation of sleep-wakefulness flip-flop in the central nervous system. Most of the VLPO neurons are sleep-promoting neurons, which co-express γ-aminobutyric acid (GABA) and galanin, while TMN neurons express histamine (HA), a key wake-promoting neurotransmitter. Previous studies have shown that the two regions are innervated between each other, but how to regulate the sleep-wake cycle are not yet clear. Here, bicuculline (Bic), a GABAA-receptor antagonist, L-glutamate (L-Glu), an excitatory neurotransmitter, and triprolidine (Trip), a HA1 receptor (HRH1) inhibitor, were bilaterally microinjected into TMN or VLPO after surgically implanting the electroencephalogram (EEG) and electromyography (EMG) electrode recording system. Microinjecting L-Glu into VLPO during the night significantly increased the NREM sleep time, and this phenomenon was weakened after selectively blocking GABAA receptors with Bic microinjected into TMN. Those results reveal that VLPO neurons activated, which may inhibit TMN neurons inducing sleep via GABAA receptors. On the contrary, exciting TMN neurons by L-Glu during the day, the wakefulness time was significantly increased. These phenomena were reversed by blocking HRH1 with Trip microinjected into VLPO. Those results reveal that TMN neuron activating may manipulate VLPO neurons via HRH1, and induce wakefulness. In conclusion, VLPO GABAergic neurons and TMN histaminergic neurons may interact with each other in regulating the sleep-wake cycle.

scholarly journals Pathway-dependent regulation of sleep dynamics in a network model of the sleep-wake cycle

2019 ◽  
Author(s):  
Charlotte Héricé ◽  
Shuzo Sakata
Keyword(s):  
Computational Model ◽  
Eye Movement ◽  
Network Model ◽  
Rem Sleep ◽  
Synaptic Weight ◽  
Nrem Sleep ◽  
Cell Types ◽  
Brain Areas ◽  
Neuronal Populations ◽  
Neural Populations

AbstractSleep is a fundamental homeostatic process within the animal kingdom. Although various brain areas and cell types are involved in the regulation of the sleep-wake cycle, it is still unclear how different pathways between neural populations contribute to its regulation. Here we address this issue by investigating the behavior of a simplified network model upon synaptic weight manipulations. Our model consists of three neural populations connected by excitatory and inhibitory synapses. Activity in each population is described by a firing-rate model, which determines the state of the network. Namely wakefulness, rapid eye movement (REM) sleep or non-REM (NREM) sleep. By systematically manipulating the synaptic weight of every pathway, we show that even this simplified model exhibits non-trivial behaviors: for example, the wake-promoting population contributes not just to the induction and maintenance of wakefulness, but also to sleep induction. Although a recurrent excitatory connection of the REM-promoting population is essential for REM sleep genesis, this recurrent connection does not necessarily contribute to the maintenance of REM sleep. The duration of NREM sleep can be shortened or extended by changes in the synaptic strength of the pathways from the NREM-promoting population. In some cases, there is an optimal range of synaptic strengths that affect a particular state, implying that the amount of manipulations, not just direction (i.e., activation or inactivation), needs to be taken into account. These results demonstrate pathway-dependent regulation of sleep dynamics and highlight the importance of systems-level quantitative approaches for sleep-wake regulatory circuits.Author SummarySleep is essential and ubiquitous across animal species. Over the past half-century, various brain areas, cell types, neurotransmitters, and neuropeptides have been identified as part of a sleep-wake regulating circuitry in the brain. However, it is less explored how individual neural pathways contribute to the sleep-wake cycle. In the present study, we investigate the behavior of a computational model by altering the strength of connections between neuronal populations. This computational model is comprised of a simple network where three neuronal populations are connected together, and the activity of each population determines the current state of the model, that is, wakefulness, rapid-eye-movement (REM) sleep or non-REM (NREM) sleep. When we alter the connection strength of each pathway, we observe that the effect of such alterations on the sleep-wake cycle is highly pathway-dependent. Our results provide further insights into the mechanisms of sleep-wake regulation, and our computational approach can complement future biological experiments.

scholarly journals Thyrotropin-releasing hormone-containing axons innervate histaminergic neurons in the tuberomammillary nucleus

2012 ◽  
Vol 1488 ◽  
pp. 72-80 ◽  
Author(s):  
Anna Sárvári ◽  
Erzsébet Farkas ◽  
Andrea Kádár ◽  
Györgyi Zséli ◽  
Tamás Füzesi ◽  
...  
Keyword(s):  
Thyrotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Tuberomammillary Nucleus ◽  
Histaminergic Neurons

Whole Cell Recordings From Visualized Neurons in the Inner Laminae of the Functionally Intact Spinal Cord

2009 ◽  
Vol 102 (1) ◽  
pp. 590-597 ◽  
Author(s):  
Jason Dyck ◽  
Simon Gosgnach
Keyword(s):  
Neural Network ◽  
Spinal Cord ◽  
Locomotor Activity ◽  
Patch Clamp ◽  
Lumbar Spinal Cord ◽  
Whole Cell ◽  
Neuronal Populations ◽  
Cell Patch Clamp ◽  
Whole Cell Patch Clamp

The in vitro whole spinal cord preparation has been an invaluable tool for the study of the neural network that underlies walking because it provides a means of recording fictive locomotor activity following surgical and/or pharmacological manipulation. The recent use of molecular genetic techniques to identify discrete neuronal populations in the spinal cord and subsequent studies showing some of these populations to be involved in locomotor activity have been exciting developments that may lead to a better understanding of the structure and mechanism of function of this neural network. It would be of great benefit if the in vitro whole spinal cord preparation could be updated to allow for the direct targeting of genetically defined neuronal populations, allowing each to be characterized physiologically and anatomically. This report describes a new technique that enables the visualization of, and targeted whole cell patch-clamp recordings from, genetically defined populations of neurons while leaving connectivity largely intact. The key feature of this technique is a small notch cut in the lumbar spinal cord that reveals cells located in the intermediate laminae while leaving the ventral portion of the spinal cord—the region containing the locomotor neural network—untouched. Whole cell patch-clamp recordings demonstrate that these neurons are healthy and display large rhythmic depolarizations that are related to electroneurogram bursts recorded from ventral roots during fictive locomotion. Intracellular labeling demonstrates that this technique can also be used to map axonal projection patterns of neurons. We expect that this procedure will greatly facilitate electrophysiological and anatomical study of important neuronal populations that constitute neural networks throughout the CNS.

Changes in the circadian rhythm of spontaneous locomotor activity and drinking behavior by brain histamine depletion

1988 ◽  
Vol 7 ◽  
pp. S190
Author(s):  
Nobuko Itowi ◽  
Atsushi Yamatodani ◽  
Junji Kishino ◽  
Katsuya Nagai ◽  
Hachiro Nakagawa ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Locomotor Activity ◽  
Drinking Behavior ◽  
Spontaneous Locomotor Activity ◽  
Brain Histamine

scholarly journals MATHEMATICAL PHASE MODEL OF NEURAL POPULATIONS INTERACTION IN MODULATION OF REM/NREM SLEEP

2016 ◽  
Vol 21 (6) ◽  
pp. 794-810 ◽  
Author(s):  
Paolo Acquistapace ◽  
Anna P. Candeloro ◽  
Vladimir Georgiev ◽  
Maria L. Manca
Keyword(s):  
Experimental Data ◽  
Eye Movement ◽  
Rem Sleep ◽  
Reaction Diffusion ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Neuronal Populations ◽  
Neural Populations ◽  
Cyclic Oscillation

Aim of the present study is to compare the synchronization of the classical Kuramoto system and the reaction - diffusion space time Landau - Ginzburg model, in order to describe the alternation of REM (rapid eye movement) and NREM (non-rapid eye movement) sleep across the night. These types of sleep are considered as produced by the cyclic oscillation of two neuronal populations that, alternatively, promote and inhibit the REM sleep. Even if experimental data will be necessary, a possible interpretation of the results has been proposed.

scholarly journals Deficiency of the RII  subunit of PKA affects locomotor activity and energy homeostasis in distinct neuronal populations

2013 ◽  
Vol 110 (17) ◽  
pp. E1631-E1640 ◽  
Author(s):  
R. Zheng ◽  
L. Yang ◽  
M. A. Sikorski ◽  
L. C. Enns ◽  
T. A. Czyzyk ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Energy Homeostasis ◽  
Neuronal Populations

scholarly journals Dual orexin and MCH neuron-ablated mice display severe sleep attacks and cataplexy

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Chi Jung Hung ◽  
Daisuke Ono ◽  
Thomas S Kilduff ◽  
Akihiro Yamanaka
Keyword(s):  
Transgenic Mice ◽  
Spectral Power ◽  
Nrem Sleep ◽  
Functional Interaction ◽  
Neuronal Populations ◽  
Orexin Neuron ◽  
Melanin Concentrating Hormone ◽  
The Brain ◽  
Theta Range

Orexin/hypocretin-producing and melanin-concentrating hormone-producing (MCH) neurons are co-extensive in the hypothalamus and project throughout the brain to regulate sleep/wakefulness. Ablation of orexin neurons decreases wakefulness and results in a narcolepsy-like phenotype, whereas ablation of MCH neurons increases wakefulness. Since it is unclear how orexin and MCH neurons interact to regulate sleep/wakefulness, we generated transgenic mice in which both orexin and MCH neurons could be ablated. Double-ablated mice exhibited increased wakefulness and decreased both rapid eye movement (REM) and non-REM (NREM) sleep. Double-ablated mice showed severe cataplexy compared with orexin neuron-ablated mice, suggesting that MCH neurons normally suppress cataplexy. Double-ablated mice also showed frequent sleep attacks with elevated spectral power in the delta and theta range, a unique state that we call ‘delta-theta sleep’. Together, these results indicate a functional interaction between orexin and MCH neurons in vivo that suggests the synergistic involvement of these neuronal populations in the sleep/wakefulness cycle.

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