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 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 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.

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.

scholarly journals Histaminergic neurotransmission as a gateway for the effects of the fat sensing molecule Oleoylethanolamide

2019 ◽  
Author(s):  
Alessia Costa
Keyword(s):  
New Drugs ◽  
Fat Intake ◽  
High Fat ◽  
Signal Molecule ◽  
Brain Histamine ◽  
Histaminergic Neurons ◽  
Aversive Events ◽  
Neuronal Mechanisms ◽  
Potential Interactions ◽  
Shed Light

The histaminergic system is a pleiotropic system that commands general states of metabolism and consciousness, including learning and memorizing both pleasurable and aversive events. Brain histamine mediates the central effects of a signal molecule produced in the intestine, namely oleoylethanolamide (OEA). OEA is released by the enterocytes in response to high fat intake and reduces eating, by indirectly activating a subpopulation of histaminergic neurons. In her thesis, she explored other potential interactions between these two systems in the pursuit of unexplored neuronal mechanisms that may shed light on the mode of action of psychoactive agents and possibly lead to the development of new drugs.

scholarly journals Role of POMC and AgRP neuronal activities on glycaemia in mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Aykut Göktürk Üner ◽  
Onur Keçik ◽  
Paula G. F. Quaresma ◽  
Thiago M. De Araujo ◽  
Hyon Lee ◽  
...  
Keyword(s):  
Neuronal Firing ◽  
Designer Drugs ◽  
Lower Blood Glucose ◽  
Glucose Lowering ◽  
Glucose Levels ◽  
Neuronal Populations ◽  
Blood Glucose Levels ◽  
Lower Blood ◽  
Stimulation Of

Abstract Leptin regulates both feeding and glycaemia primarily through its receptors expressed on agouti-related peptide (AgRP) and pro-opiomelanocortin-expressing (POMC) neurons; however, it is unknown whether activity of these neuronal populations mediates the regulation of these processes. To determine this, we injected Cre-dependent designer receptors exclusively activated by designer drugs (DREADD) viruses into the hypothalamus of normoglycaemic and diabetic AgRP-ires-cre and POMC-cre mice to chemogenetically activate or inhibit these neuronal populations. Despite robust changes in food intake, activation or inhibition of AgRP neurons did not affect glycaemia, while activation caused significant (P = 0.014) impairment in insulin sensitivity. Stimulation of AgRP neurons in diabetic mice reversed leptin’s ability to inhibit feeding but did not counter leptin’s ability to lower blood glucose levels. Notably, the inhibition of POMC neurons stimulated feeding while decreasing glucose levels in normoglycaemic mice. The findings suggest that leptin’s effects on feeding by AgRP neurons are mediated by changes in neuronal firing, while the control of glucose balance by these cells is independent of chemogenetic activation or inhibition. The firing-dependent glucose lowering mechanism within POMC neurons is a potential target for the development of novel anti-diabetic medicines.

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