scholarly journals Role of Endogenous Cannabinoids in Synaptic Signaling

2003 ◽  
Vol 83 (3) ◽  
pp. 1017-1066 ◽  
Author(s):  
TAMÁS F. FREUND ◽  
ISTVÁN KATONA ◽  
DANIELE PIOMELLI
Keyword(s):  
Neurotransmitter Release ◽  
Cannabinoid Receptor ◽  
Activity Patterns ◽  
Physiological Effect ◽  
Network Activity ◽  
Signal Molecules ◽  
Synaptic Signaling ◽  
Endogenous Cannabinoids ◽  
The Brain

Freund, Tamás F., István Katona, and Daniele Piomelli. Role of Endogenous Cannabinoids in Synaptic Signaling. Physiol Rev 83: 1017–1066, 2003; 10.1152/physrev.00004.2003.—Research of cannabinoid actions was boosted in the 1990s by remarkable discoveries including identification of endogenous compounds with cannabimimetic activity (endocannabinoids) and the cloning of their molecular targets, the CB1 and CB2 receptors. Although the existence of an endogenous cannabinoid signaling system has been established for a decade, its physiological roles have just begun to unfold. In addition, the behavioral effects of exogenous cannabinoids such as delta-9-tetrahydrocannabinol, the major active compound of hashish and marijuana, await explanation at the cellular and network levels. Recent physiological, pharmacological, and high-resolution anatomical studies provided evidence that the major physiological effect of cannabinoids is the regulation of neurotransmitter release via activation of presynaptic CB1 receptors located on distinct types of axon terminals throughout the brain. Subsequent discoveries shed light on the functional consequences of this localization by demonstrating the involvement of endocannabinoids in retrograde signaling at GABAergic and glutamatergic synapses. In this review, we aim to synthesize recent progress in our understanding of the physiological roles of endocannabinoids in the brain. First, the synthetic pathways of endocannabinoids are discussed, along with the putative mechanisms of their release, uptake, and degradation. The fine-grain anatomical distribution of the neuronal cannabinoid receptor CB1 is described in most brain areas, emphasizing its general presynaptic localization and role in controlling neurotransmitter release. Finally, the possible functions of endocannabinoids as retrograde synaptic signal molecules are discussed in relation to synaptic plasticity and network activity patterns.

scholarly journals The role of CYP2D in rat brain in methamphetamine-induced striatal dopamine and serotonin release and behavioral sensitization

2021 ◽  
Author(s):  
Marlaina R. Stocco ◽  
Ahmed A. El-Sherbeni ◽  
Bin Zhao ◽  
Maria Novalen ◽  
Rachel F. Tyndale
Keyword(s):  
Neurotransmitter Release ◽  
Behavioral Sensitization ◽  
Serotonin Release ◽  
Striatal Dopamine ◽  
Irreversible Inhibitor ◽  
Drug Concentrations ◽  
Metabolite Concentrations ◽  
The Brain

Abstract Rationale Cytochrome P450 2D (CYP2D) enzymes metabolize many addictive drugs, including methamphetamine. Variable CYP2D metabolism in the brain may alter CNS drug/metabolite concentrations, consequently affecting addiction liability and neuropsychiatric outcomes; components of these can be modeled by behavioral sensitization in rats. Methods To investigate the role of CYP2D in the brain in methamphetamine-induced behavioral sensitization, rats were pretreated centrally with a CYP2D irreversible inhibitor (or vehicle) 20 h prior to each of 7 daily methamphetamine (0.5 mg/kg subcutaneous) injections. In vivo brain microdialysis was used to assess brain drug and metabolite concentrations, and neurotransmitter release. Results CYP2D inhibitor (versus vehicle) pretreatment enhanced methamphetamine-induced stereotypy response sensitization. CYP2D inhibitor pretreatment increased brain methamphetamine concentrations and decreased the brain p-hydroxylation metabolic ratio. With microdialysis conducted on days 1 and 7, CYP2D inhibitor pretreatment exacerbated stereotypy sensitization and enhanced dopamine and serotonin release in the dorsal striatum. Day 1 brain methamphetamine and amphetamine concentrations correlated with dopamine and serotonin release, which in turn correlated with the stereotypy response slope across sessions (i.e., day 1 through day 7), used as a measure of sensitization. Conclusions CYP2D-mediated methamphetamine metabolism in the brain is sufficient to alter behavioral sensitization, brain drug concentrations, and striatal dopamine and serotonin release. Moreover, day 1 methamphetamine-induced neurotransmitter release may be an important predictor of subsequent behavioral sensitization. This suggests the novel contribution of CYP2D in the brain to methamphetamine-induced behavioral sensitization and suggests that the wide variation in human brain CYP2D6 may contribute to differential methamphetamine responses and chronic effects.

scholarly journals Neuronal circuits overcome imbalance in excitation and inhibition by adjusting connection numbers

2021 ◽  
Vol 118 (12) ◽  
pp. e2018459118
Author(s):  
Nirit Sukenik ◽  
Oleg Vinogradov ◽  
Eyal Weinreb ◽  
Menahem Segal ◽  
Anna Levina ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Activity ◽  
Network Activity ◽  
Neuronal Circuitry ◽  
Inhibitory Cell ◽  
Single Cell Activity ◽  
Hippocampal Cultures ◽  
Cell Fractions ◽  
The Brain

The interplay between excitation and inhibition is crucial for neuronal circuitry in the brain. Inhibitory cell fractions in the neocortex and hippocampus are typically maintained at 15 to 30%, which is assumed to be important for stable dynamics. We have studied systematically the role of precisely controlled excitatory/inhibitory (E/I) cellular ratios on network activity using mice hippocampal cultures. Surprisingly, networks with varying E/I ratios maintain stable bursting dynamics. Interburst intervals remain constant for most ratios, except in the extremes of 0 to 10% and 90 to 100% inhibitory cells. Single-cell recordings and modeling suggest that networks adapt to chronic alterations of E/I compositions by balancing E/I connectivity. Gradual blockade of inhibition substantiates the agreement between the model and experiment and defines its limits. Combining measurements of population and single-cell activity with theoretical modeling, we provide a clearer picture of how E/I balance is preserved and where it fails in living neuronal networks.

Role of AMPA Receptor Desensitization and the Side Effects of a DMSO Vehicle on Reticulospinal EPSPs and Locomotor Activity

2005 ◽  
Vol 94 (6) ◽  
pp. 3951-3960 ◽  
Author(s):  
Nataliya A. Tsvyetlynska ◽  
Russell H. Hill ◽  
Sten Grillner
Keyword(s):  
Nmda Receptors ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Pattern Generation ◽  
Network Activity ◽  
Excitatory Postsynaptic Potential ◽  
Receptor Desensitization ◽  
Neuronal Network Activity ◽  
The Brain

Activation of the vertebrate locomotor network is mediated by glutamatergic synaptic drive, normally initiated by the brain stem. Previous investigations have studied the role of glutamate receptors, especially NMDA receptors, in generating and regulating locomotor pattern generation. Few studies, however, have focused on the role of AMPA receptors in shaping network activity, especially with regard to their rapid desensitization. It is important to determine whether AMPA receptor desensitization plays a role in regulating neuronal network activity. We examined this question on both the network and synaptic levels in the lamprey ( Lampetra fluviatilis) spinal cord using a selective and potent inhibitor of AMPA receptor desensitization, cyclothiazide (CTZ). The solvent dimethyl sulfoxide (DMSO) is commonly used to dissolve this drug, as well as many others. Unexpectedly, the vehicle alone already at 0.02%, but not at 0.01%, caused significant increases in excitatory postsynaptic potential (EPSP) amplitudes and NMDA-induced locomotor frequency. The results indicate that DMSO may have a profound influence when used ≥0.02%, a concentration 10–50 times less than that most commonly used. Subsequently we applied CTZ concentrations ≤10 μM (DMSO ≤0.01%). CTZ (1.25–5 μM) caused an appreciable and significant increase in EPSPs mediated by non-NMDA receptors and in both AMPA- and NMDA-induced locomotor frequency, but no effects on EPSPs mediated by NMDA receptors. From the effects of CTZ it is apparent that AMPA receptor desensitization plays an important role in determining locomotor frequency and that this is likely a result of its limiting function on AMPA receptor–mediated EPSPs.

scholarly journals Role of Cannabinoid Receptor in the Brain as It Relates to Drug Reward

2000 ◽  
Vol 84 (3) ◽  
pp. 229-236 ◽  
Author(s):  
Tsuneyuki Yamamoto ◽  
Kohji Takada
Keyword(s):  
Cannabinoid Receptor ◽  
Drug Reward ◽  
The Brain

scholarly journals Whole-central nervous system functional imaging in larval Drosophila

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
William C. Lemon ◽  
Stefan R. Pulver ◽  
Burkhard Höckendorf ◽  
Katie McDole ◽  
Kristin Branson ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nerve Cord ◽  
Ventral Nerve Cord ◽  
Activity Patterns ◽  
Network Activity ◽  
Imaging Data ◽  
Spatiotemporal Resolution ◽  
Functional Connections ◽  
The Brain

Abstract Understanding how the brain works in tight concert with the rest of the central nervous system (CNS) hinges upon knowledge of coordinated activity patterns across the whole CNS. We present a method for measuring activity in an entire, non-transparent CNS with high spatiotemporal resolution. We combine a light-sheet microscope capable of simultaneous multi-view imaging at volumetric speeds 25-fold faster than the state-of-the-art, a whole-CNS imaging assay for the isolated Drosophila larval CNS and a computational framework for analysing multi-view, whole-CNS calcium imaging data. We image both brain and ventral nerve cord, covering the entire CNS at 2 or 5 Hz with two- or one-photon excitation, respectively. By mapping network activity during fictive behaviours and quantitatively comparing high-resolution whole-CNS activity maps across individuals, we predict functional connections between CNS regions and reveal neurons in the brain that identify type and temporal state of motor programs executed in the ventral nerve cord.

Interactions of Excitatory and Inhibitory Feedback Topologies in Facilitating Pattern Separation and Retrieval

2012 ◽  
Vol 24 (1) ◽  
pp. 32-59
Author(s):  
Jane X. Wang ◽  
Michal Zochowski
Keyword(s):  
Memory Management ◽  
Activity Patterns ◽  
Pattern Separation ◽  
Memory Recall ◽  
Cognitive States ◽  
Management Processes ◽  
Inhibitory Feedback ◽  
Global And Local ◽  
The Brain

Within the brain, the interplay between connectivity patterns of neurons and their spatiotemporal dynamics is believed to be intricately linked to the bases of behavior, such as the process of storing, consolidating, and retrieving memory traces. Memory is believed to be stored in the synaptic patterns of anatomical circuitry in the form of increased connectivity densities within subpopulations of neurons. At the same time, memory recall is thought to correspond to activation of discrete areas of the brain corresponding to those memories. Such regional subpopulations can selectively activate during memory recall or retrieval, signifying the process of accessing a single memory or concept. It has been shown previously that recovery of single memory activity patterns is mediated by global neuromodulation signifying transition into different cognitive states such as sleep or awake exploration. We examine how underlying topology can affect memory awake activation and sleep reactivation when such memories share increasing proportions of neurons. The results show that while single memory activation is diminished with increased overlap, pattern separation can be recovered by offsetting excitatory associations between two memories with targeted and heterogeneous inhibitory feedback. Such findings point to the importance of excitatory-to-inhibitory current balance at both the global and local levels in the context of memory retrieval and replay, and highlight the role of network topology in memory management processes.

scholarly journals The role of piriform associative connections in odor categorization

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Xiaojun Bao ◽  
Louise LG Raguet ◽  
Sydni M Cole ◽  
James D Howard ◽  
Jay A Gottfried
Keyword(s):  
Activity Patterns ◽  
Piriform Cortex ◽  
Discrimination Performance ◽  
Object Identification ◽  
Pattern Separation ◽  
Odor Perception ◽  
Drug Induced ◽  
Multivariate Pattern ◽  
The Brain

Distributed neural activity patterns are widely proposed to underlie object identification and categorization in the brain. In the olfactory domain, pattern-based representations of odor objects are encoded in piriform cortex. This region receives both afferent and associative inputs, though their relative contributions to odor perception are poorly understood. Here, we combined a placebo-controlled pharmacological fMRI paradigm with multivariate pattern analyses to test the role of associative connections in sustaining olfactory categorical representations. Administration of baclofen, a GABA(B) agonist known to attenuate piriform associative inputs, interfered with within-category pattern separation in piriform cortex, and the magnitude of this drug-induced change predicted perceptual alterations in fine-odor discrimination performance. Comparatively, baclofen reduced pattern separation between odor categories in orbitofrontal cortex, and impeded within-category generalization in hippocampus. Our findings suggest that odor categorization is a dynamic process concurrently engaging stimulus discrimination and generalization at different stages of olfactory information processing, and highlight the importance of associative networks in maintaining categorical boundaries.

The Functional Role of Large-scale Brain Network Coordination in Placebo-induced Anxiolysis

2018 ◽  
Vol 29 (8) ◽  
pp. 3201-3210 ◽  
Author(s):  
Benjamin Meyer ◽  
Kenneth S L Yuen ◽  
Victor Saase ◽  
Raffael Kalisch
Keyword(s):  
Functional Role ◽  
Large Scale ◽  
Activity Patterns ◽  
Clinical Importance ◽  
Mental States ◽  
Brain Network ◽  
Anxiety Reduction ◽  
Anterior Cingulate ◽  
Network Activity

Abstract Anxiety reduction through mere expectation of anxiolytic treatment effects (placebo anxiolysis) has enormous clinical importance. Recent behavioral and electrophysiological data suggest that placebo anxiolysis involves reduced vigilance and enhanced internalization of attention; however, the underlying neurobiological mechanisms are not yet clear. Given the fundamental function of intrinsic connectivity networks (ICNs) in basic cognitive processes, we investigated ICN activity patterns associated with externally and internally directed mental states under the influence of an anxiolytic placebo medication. Based on recent findings, we specifically analyzed the functional role of the rostral anterior cingulate cortex (rACC) in coordinating placebo-dependent cue-related (phasic) and cue-unrelated (sustained) network activity. Under placebo, we observed a down-regulation of the entire salience network (SN), particularly in response to threatening cues. The rACC exhibited enhanced cue-unrelated functional connectivity (FC) with the SN, which correlated with reductions in tonic arousal and anxiety. Hence, apart from the frequently reported modulation of aversive cue responses, the rACC appears to be crucially involved in exerting a tonically dampening control over salience-responsive structures. In line with a more internally directed mental state, we also found enhanced FC within the default mode network (DMN), again predicting reductions in anxiety under placebo.

Feelings About Thoughts, Time, and Me

2014 ◽  
Author(s):  
A. D. (Bud) Craig
Keyword(s):  
Functional Role ◽  
Fluid Intelligence ◽  
Insular Cortex ◽  
Energy Utilization ◽  
Network Activity ◽  
Anterior Insular Cortex ◽  
Subjective Awareness ◽  
The Brain

This chapter describes evidence that the anterior insular cortex (AIC) is activated during thoughts, and explains how cognitive feelings are generated in the model of interoceptive and homeostatic integration. Presenting evidence that the AIC engenders subjective awareness and feelings about time, the chapter also shows how a cinemascopic structure in the model of interoceptive feelings can produce awareness across time, as well as musical feelings and subjectivity. It argues that the key functional role of the AIC in humans is the control of network activity in the brain, then relates this concept to studies that suggest a major role of the AIC in fluid intelligence and in behavioral guidance based on energy utilization.

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