Endocannabinoid-Mediated Control of Synaptic Transmission

2009 ◽  
Vol 89 (1) ◽  
pp. 309-380 ◽  
Author(s):  
Masanobu Kano ◽  
Takako Ohno-Shosaku ◽  
Yuki Hashimotodani ◽  
Motokazu Uchigashima ◽  
Masahiko Watanabe
Keyword(s):  
Synaptic Transmission ◽  
Intracellular Signaling ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
New Era ◽  
Behavioral Studies ◽  
Electrophysiological Studies ◽  
The Brain ◽  
Subsequent Identification

The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for cannabinoid research and also established a new concept how diffusible messengers modulate synaptic efficacy and neural activity. The last 7 years have witnessed remarkable advances in our understanding of the endocannabinoid system. It is now well accepted that endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid CB1 receptors, and cause transient and long-lasting reduction of neurotransmitter release. In this review, we aim to integrate our current understanding of functions of the endocannabinoid system, especially focusing on the control of synaptic transmission in the brain. We summarize recent electrophysiological studies carried out on synapses of various brain regions and discuss how synaptic transmission is regulated by endocannabinoid signaling. Then we refer to recent anatomical studies on subcellular distribution of the molecules involved in endocannabinoid signaling and discuss how these signaling molecules are arranged around synapses. In addition, we make a brief overview of studies on cannabinoid receptors and their intracellular signaling, biochemical studies on endocannabinoid metabolism, and behavioral studies on the roles of the endocannabinoid system in various aspects of neural functions.

scholarly journals Distribution of the Cannabinoid Receptor Type 1 in the Brain of the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal

2021 ◽  
Vol 15 ◽  
Author(s):  
Alejando Fuerte-Hortigón ◽  
Jaime Gonçalves ◽  
Laura Zeballos ◽  
Rubén Masa ◽  
Ricardo Gómez-Nieto ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
Audiogenic Seizure ◽  
Type I ◽  
Sound Stimulation ◽  
Differential Distribution ◽  
Central Type ◽  
Anatomical Basis

The endocannabinoid system modulates epileptic seizures by regulating neuronal excitability. It has become clear that agonist activation of central type I cannabinoid receptors (CB1R) reduces epileptogenesis in pre-clinical animal models of epilepsy. The audiogenic seizure-prone hamster GASH/Sal is a reliable experimental model of generalized tonic-clonic seizures in response to intense sound stimulation. However, no studies hitherto had investigated CB1R in the GASH/Sal. Although the distribution of CB1R has been extensively studied in mammalian brains, their distribution in the Syrian golden hamster brain also remains unknown. The objective of this research is to determine by immunohistochemistry the differential distribution of CB1R in the brains of GASH/Sal animals under seizure-free conditions, by comparing the results with wild-type Syrian hamsters as controls. CB1R in the GASH/Sal showed a wide distribution in many nuclei of the central nervous system. These patterns of CB1R-immunolabeling are practically identical between the GASH/Sal model and control animals, varying in the intensity of immunostaining in certain regions, being slightly weaker in the GASH/Sal than in the control, mainly in brain regions associated with epileptic networks. The RT-qPCR analysis confirms these results. In summary, our study provides an anatomical basis for further investigating CB1R in acute and kindling audiogenic seizure protocols in the GASH/Sal model as well as exploring CB1R activation via exogenously administered cannabinoid compounds.

scholarly journals Sex in the brain: hormones and sex differences

2016 ◽  
Vol 18 (4) ◽  
pp. 373-383 ◽  
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Genetic Factors ◽  
Motor Coordination ◽  
Brain Regions ◽  
New Era ◽  
Brain Functions ◽  
Opioid Sensitivity ◽  
Males And Females ◽  
The Brain

Contrary to popular belief, sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Many neural and behavioral functions are affected by estrogens, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that we are entering a new era in our ability to understand and appreciate the diversity of gender-related behaviors and brain functions.

scholarly journals A review of efferent cholinergic synaptic transmission in the vestibular periphery and its functional implications

2020 ◽  
Vol 123 (2) ◽  
pp. 608-629 ◽  
Author(s):  
L. A. Poppi ◽  
J. C. Holt ◽  
R. Lim ◽  
A. M. Brichta
Keyword(s):  
Synaptic Transmission ◽  
Vestibular System ◽  
Cellular Mechanisms ◽  
Cholinergic Synaptic Transmission ◽  
Behavioral Studies ◽  
Functional Implications ◽  
Electrophysiological Studies ◽  
Efferent Vestibular System ◽  
Anatomical Characterization

It has been over 60 years since peripheral efferent vestibular terminals were first identified in mammals, and yet the function of the efferent vestibular system remains obscure. One reason for the lack of progress may be due to our deficient understanding of the peripheral efferent synapse. Although vestibular efferent terminals were identified as cholinergic less than a decade after their anatomical characterization, the cellular mechanisms that underlie the properties of these synapses have had to be inferred. In this review we examine how recent mammalian studies have begun to reveal both nicotinic and muscarinic effects at these terminals and therefore provide a context for fast and slow responses observed in classic electrophysiological studies of the mammalian efferent vestibular system, nearly 40 years ago. Although incomplete, these new results together with those of recent behavioral studies are helping to unravel the mysterious and perplexing action of the efferent vestibular system. Armed with this information, we may finally appreciate the behavioral framework in which the efferent vestibular system operates.

Memory Engrams in the Neocortex

2020 ◽  
pp. 107385842094152
Author(s):  
Svenja Brodt ◽  
Steffen Gais
Keyword(s):  
Posterior Parietal Cortex ◽  
Brain Regions ◽  
Loss Of Function ◽  
Noninvasive Methods ◽  
New Era ◽  
Parallel Memory ◽  
Memory Representations ◽  
Posterior Parietal ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

While in the past much of our knowledge about memory representations in the brain has relied on loss-of-function studies in which whole brain regions were temporarily inactivated or permanently lesioned, the recent development of new methods has ushered in a new era of downright “engram excitement.” Animal research is now able to specifically label, track, and manipulate engram cells in the brain. While early studies have mostly focused on single brain regions like the hippocampus, recently more and more evidence for brain-wide distributed engram networks is emerging. Memory research in humans has also picked up pace, fueled by promising magnetic resonance imaging (MRI)-based methods like diffusion-weighted MRI (DW-MRI) and brain decoding. In this review, we will outline recent advancements in engram research, with a focus on human data and neocortical representations. We will illustrate the available noninvasive methods for the detection of engrams in different neocortical regions like the medial prefrontal cortex and the posterior parietal cortex and discuss evidence for systems consolidation and parallel memory encoding. Finally, we will explore how reactivation and prior knowledge can lead to and enhance engram formation in the neocortex.

scholarly journals Modulation of Network Oscillatory Activity and GABAergic Synaptic Transmission by CB1 Cannabinoid Receptors in the Rat Medial Entorhinal Cortex

2008 ◽  
Vol 2008 ◽  
pp. 1-12 ◽  
Author(s):  
Nicola H. Morgan ◽  
Ian M. Stanford ◽  
Gavin L. Woodhall
Keyword(s):  
Synaptic Transmission ◽  
Cannabinoid Receptors ◽  
Brain Regions ◽  
Synaptic Activity ◽  
Network Activity ◽  
Oscillatory Activity ◽  
Gabaergic Neurotransmission ◽  
Network Oscillations ◽  
Gabaergic Synaptic Transmission

Cannabinoids modulate inhibitory GABAergic neurotransmission in many brain regions. Within the temporal lobe, cannabinoid receptors are highly expressed, and are located presynaptically at inhibitory terminals. Here, we have explored the role of type-1 cannabinoid receptors (CB1Rs) at the level of inhibitory synaptic currents and field-recorded network oscillations. We report that arachidonylcyclopropylamide (ACPA; 10 M), an agonist at CB1R, inhibits GABAergic synaptic transmission onto both superficial and deep medial entorhinal (mEC) neurones, but this has little effect on network oscillations in beta/gamma frequency bands. By contrast, the CB1R antagonist/inverse agonist LY320135 (500 nM), increased GABAergic synaptic activity and beta/gamma oscillatory activity in superficial mEC, was suppressed, whilst that in deep mEC was enhanced. These data indicate that cannabinoid-mediated effects on inhibitory synaptic activity may be constitutively active in vitro, and that modulation of CB1R activation using inverse agonists unmasks complex effects of CBR function on network activity.

Cannabinoids and the Brain

2017 ◽  
Author(s):  
Linda A. Parker
Keyword(s):  
Cannabinoid Receptors ◽  
Legal Status ◽  
Therapeutic Potential ◽  
Scientific Discovery ◽  
Scientific Evidence ◽  
Endocannabinoid System ◽  
Preclinical Research ◽  
Pain Anxiety ◽  
Scientific Investigations ◽  
The Brain

Cannabinoids and the Brain introduces an informed general audience to the scientific discovery of the endocannabinoid system and recent preclinical research that explains its importance in brain functioning. The endocannabinoids, anandamide and 2-AG, act on the same cannabinoid receptors, that are activated by the primary psychoactive compound found in marijuana, Δ‎9-tetrahydrocannabinol (THC). Therefore, the scientific investigations of the functions of the endocannabinoid system are guided by the known effects of marijuana on the brain and body. The book reviews the scientific evidence of the role that the endocannabinoid system plays in regulating emotion, anxiety, depression, psychosis, reward and addiction, learning and memory, feeding, nausea/vomiting, pain, epilepsy, and other neurological disorders. Anecdotal reports are linked with the current scientific literature on the medicinal benefits of marijuana. Cannabis contains over 80 chemicals that have closely related structures, called cannabinoids, but the only major mood-altering constituent is THC. Another major plant cannabinoid is cannabidiol (CBD), which is not psychoactive; yet, considerable recent preclinical research reviewed in various chapters reveals that CBD has promising therapeutic potential in treatment of pain, anxiety, nausea and epilepsy. Only recently, has research been conducted with some of the other compounds found in cannabis. The subject matter of the book is extremely timely in light of the current ongoing debate not only about medical marijuana, but also about its legal status.

scholarly journals Adaptive and multifunctional hydrogel hybrid probes for long-term sensing and modulation of neural activity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Seongjun Park ◽  
Hyunwoo Yuk ◽  
Ruike Zhao ◽  
Yeong Shin Yim ◽  
Eyob W. Woldeghebriel ◽  
...  
Keyword(s):  
Foreign Body ◽  
Brain Regions ◽  
Foreign Body Response ◽  
Behavioral Studies ◽  
Hydrogel Matrix ◽  
Underlying Mechanisms ◽  
Hybrid Devices ◽  
The Brain ◽  
Body Response

AbstractTo understand the underlying mechanisms of progressive neurophysiological phenomena, neural interfaces should interact bi-directionally with brain circuits over extended periods of time. However, such interfaces remain limited by the foreign body response that stems from the chemo-mechanical mismatch between the probes and the neural tissues. To address this challenge, we developed a multifunctional sensing and actuation platform consisting of multimaterial fibers intimately integrated within a soft hydrogel matrix mimicking the brain tissue. These hybrid devices possess adaptive bending stiffness determined by the hydration states of the hydrogel matrix. This enables their direct insertion into the deep brain regions, while minimizing tissue damage associated with the brain micromotion after implantation. The hydrogel hybrid devices permit electrophysiological, optogenetic, and behavioral studies of neural circuits with minimal foreign body responses and tracking of stable isolated single neuron potentials in freely moving mice over 6 months following implantation.

Cannabidiolɗs Role as a Potential Target in the Treatment for Schizophrenia

2017 ◽  
Vol 41 (S1) ◽  
pp. S631-S631
Author(s):  
A. Carvalho ◽  
J. Felgueiras ◽  
T. Abreu ◽  
C. Freitas ◽  
J. Silva
Keyword(s):  
Endocannabinoid System ◽  
Brain Regions ◽  
Great Promise ◽  
Novel Therapy ◽  
Considerable Uncertainty ◽  
Wide Range ◽  
Competing Interest ◽  
The Individual ◽  
The Brain

ObjectivesSchizophrenia is a debilitating psychiatric disorder which places a significant emotional and economic strain on the individual and society-at-large. Unfortunately, currently available therapeutic strategies do not provide adequate relief and some patients are treatment-resistant. Therefore there is urgent need for the development of mechanistically different and less side effect prone antipsychotic compounds. Recently, the endocannabinoid system has emerged as a potential therapeutic target for pharmacotherapy that is involved in a wide range of disorders, including schizophrenia. Modulation of this system by the main psychoactive component in cannabis, Δ9tetrahydrocannabinol (THC), induces acute psychotic effects and cognitive impairment. However, the non-psychotropic, plant-derived cannabinoid agent cannabidiol shows great promise for the treatment of psychosis, and is associated with fewer extrapyramidal side effects than conventional antipsychotic drugs.MethodsThe aim of this review is to analyse the involvement of the endocannabinoid system in schizophrenia and the potential role of cannabidiol in its treatment.Results and conclusionsThere is still considerable uncertainty about the mechanism of action of cannabidiol as well as the brain regions which are thought to mediate its putative antipsychotic effect. Further data is warrant before this novel therapy can be introduced into clinical practice.Disclosure of interestThe authors have not supplied their declaration of competing interest

scholarly journals A Brief Background on Cannabis: From Plant to Medical Indications

2019 ◽  
Vol 102 (2) ◽  
pp. 412-420 ◽  
Author(s):  
Linda E Klumpers ◽  
David L Thacker
Keyword(s):  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Good Evidence ◽  
The Body ◽  
Post Traumatic Stress ◽  
History Of ◽  
Post Traumatic ◽  
Loss Of Appetite ◽  
Medical Indications ◽  
The Brain

Abstract Cannabis has been used as a medicinal plant for thousands of years. As a result of centuries of breeding and selection, there are now over 700 varieties of cannabis that contain hundreds of compounds, including cannabinoids and terpenes. Cannabinoids are fatty compounds that are the main biological active constituents of cannabis. Terpenes are volatilecompounds that occur in many plants and have distinct odors. Cannabinoids exert their effect on the body by binding to receptors, specifically cannabinoid receptors types 1 and 2. These receptors, together with endogenous cannabinoids and the systems forsynthesis, transport, and degradation, are called the Endocannabinoid System. The two most prevalent and commonly known cannabinoids in the cannabis plantare delta-9-tetrahydrocannabinol (THC) and cannabidiol. The speed, strength, and type of effects of cannabis vary based on the route of administration. THC is rapidly distributed through the body to fattytissues like the brain and is metabolized by the cytochrome P450 system to 11-hydroxy-THC, which is also psychoactive. Cannabis and cannabinoids have been indicated for several medical conditions. There is evidence of efficacy in the symptomatic treatmentof nausea and vomiting, pain, insomnia, post-traumatic stress disorder, anxiety, loss of appetite, Tourette’s syndrome, and epilepsy. Cannabis hasalso been associated with treatment for glaucoma, Huntington’s Disease, Parkinson’s Disease, and dystonia, but thereis not good evidence tosupport its efficacy. Side effects of cannabis include psychosis and anxiety, which can be severe. Here, we provided a summary ofthe history of cannabis,its pharmacology, and its medical uses.

scholarly journals Inherent Sex Differences in the Expression of the Endocannabinoid System within V1M Cortex and PAG of Sprague Dawley Rats

2021 ◽  
Author(s):  
Aidan Levine ◽  
Erika Liktor-Busa ◽  
Austin A Lipinski ◽  
Sarah Couture ◽  
Shreya Balasubramanian ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Chronic Pain ◽  
Sex Differences ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
Sprague Dawley ◽  
Female Population ◽  
Sprague Dawley Rats ◽  
Chronic Pain Conditions

Abstract Background: Several chronic pain disorders, such as migraine and fibromyalgia, have an increased prevalence in the female population. The underlying mechanisms of this sex-biased prevalence have yet to be thoroughly documented but could be related to endogenous differences in neuromodulators in pain networks, including the endocannabinoid system. The cellular endocannabinoid system is comprised of the endogenous lipid signals 2-AG (2-arachidonoylglycerol) and AEA (anandamide); the enzymes that synthesize and degrade them; and the cannabinoid receptors. The relative prevalence of different components of the endocannabinoid system in specific brain regions may alter responses to endogenous and exogenous ligands. Methods: Brain tissue from naïve male and female Sprague Dawley rats was harvested from V1M cortex, periaqueductal gray, trigeminal nerve, and trigeminal nucleus caudalis. Tissue was analyzed for relative levels of endocannabinoid enzymes, ligands, and receptors via mass spectrometry, unbiased proteomic analysis, and immunohistochemistry. Results: Mass spectrometry revealed cortical AEA levels were significantly higher in males compared to females (p<0.001), whereas 2-AG levels in periaqueductal grey were significantly higher in females compared to males (p<0.0001). Immunohistochemistry followed by unbiased proteomics confirmed the prevalence of 2-AG-endocannabinoid system enzymes in the female PAG.Conclusions: Our results suggest that sex differences exist in the endocannabinoid system in two CNS regions relevant to cortical spreading depression (V1M cortex) and descending modulatory networks in pain/anxiety (PAG). These basal differences in endogenous endocannabinoid mechanisms may facilitate the development of chronic pain conditions and may also underlie sex differences in response to therapeutic intervention.

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