scholarly journals Cholecystokinin-mediated Neuromodulation of Anxiety and Schizophrenia: A “Dimmer-Switch” Hypothesis

2020 ◽  
Vol 18 ◽  
Author(s):  
Santiago J. Ballaz ◽  
Michel Bourin
Keyword(s):  
Neural Activity ◽  
Panic Attacks ◽  
Inhibitory Interneurons ◽  
Cortical Dynamics ◽  
Reward Circuitry ◽  
Cognitive Component ◽  
Dopaminergic Systems ◽  
The Brain ◽  
Cck2 Receptor ◽  
Cck Release

: Cholecystokin (CCK), the most abundant brain neuropeptide, is involved in relevant behavioral functions like memory, cognition, and reward through its interactions with the opioid and dopaminergic systems in the limbic system. CCK excites neurons by binding two receptors, CCK1 and CCK2, expressed at low and high levels in the brain, respectively. Historically, CCK2 receptors have been related to the induction of panic attacks in humans. Disturbances in brain CCK expression also underlie the physiopathology of schizophrenia, which is attributed to the modulation by CCK1 receptors of the dopamine flux in the basal striatum. Despite this evidence, neither CCK2 receptor antagonists ameliorate human anxiety nor have CCK agonists consistently shown neuroleptic effects in clinical trials. A neglected aspect of the function of brain CCK is its neuromodulatory role in mental disorders. Interestingly, CCK is expressed in pivotal inhibitory interneurons that sculpt cortical dynamics and the flux of nerve impulses across corticolimbic areas and the excitatory projections to mesolimbic pathways. At the basal striatum, CCK modulates the excitability of glutamate, the release of inhibitory GABA, and the discharge of dopamine. Here we focus on how CCK may reduce rather than trigger anxiety by regulating its cognitive component. Adequate levels of CCK release in the basal striatum may control the interplay between cognition and reward circuitry, which is critical in schizophrenia. Hence, it is proposed that disturbances in the excitatory/inhibitory interplay modulated by CCK may contribute to the imbalanced interaction between corticolimbic and mesolimbic neural activity found in anxiety and schizophrenia.

scholarly journals Cholecystokinin and Panic Disorder: Reflections on the History and Some Unsolved Questions

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5657
Author(s):  
Jens F. Rehfeld
Keyword(s):  
Panic Disorder ◽  
Panic Attacks ◽  
Normal Brain ◽  
Brain Functions ◽  
Gut Hormone ◽  
Neuropsychiatric Diseases ◽  
The Common ◽  
Almost All ◽  
The Brain ◽  
Cck2 Receptor

The classic gut hormone cholecystokinin (CCK) and its CCK2-receptor are expressed in almost all regions of the brain. This widespread expression makes CCK by far the most abundant peptidergic transmitter system in the brain. This CNS-ubiquity has, however, complicated the delineation of the roles of CCK peptides in normal brain functions and neuropsychiatric diseases. Nevertheless, the common panic disorder disease is apparently associated with CCK in the brain. Thus, the C-terminal tetrapeptide fragment of CCK (CCK-4) induces, by intravenous administration in a dose-related manner, panic attacks that are similar to the endogenous attacks in panic disorder patients. This review describes the history behind the discovery of the panicogenic effect of CCK-4. Subsequently, the review discusses three unsettled questions about the involvement of cerebral CCK in the pathogenesis of anxiety and panic disorder, including therapeutic attempts with CCK2-receptor antagonists.

Magnetoencephalography and the Cortical Dynamics of Language Processing

2019 ◽  
pp. 114-153
Author(s):  
Riitta Salmelin ◽  
Jan Kujala ◽  
Mia Liljeström
Keyword(s):  
Language Processing ◽  
Language Disorders ◽  
Scientific Data ◽  
Neural Processing ◽  
Powerful Method ◽  
Cortical Dynamics ◽  
Brain Correlates ◽  
Adults And Children ◽  
The Brain ◽  
Selection Of

When seeking to uncover the brain correlates of language processing, timing and location are of the essence. Magnetoencephalography (MEG) offers them both, with the highest sensitivity to cortical activity. MEG has shown its worth in revealing cortical dynamics of reading, speech perception, and speech production in adults and children, in unimpaired language processing as well as developmental and acquired language disorders. The MEG signals, once recorded, provide an extensive selection of measures for examination of neural processing. Like all other neuroimaging tools, MEG has its own strengths and limitations of which the user should be aware in order to make the best possible use of this powerful method and to generate meaningful and reliable scientific data. This chapter reviews MEG methodology and how MEG has been used to study the cortical dynamics of language.

scholarly journals Synergistic Effect of Several Neurotransmitters in PFC-NAc-VTA Neural Circuit for the Anti-Depression Effect of Shuganheweitang in a Chronic Unpredictable Mild Stress Model

2021 ◽  
Vol 16 (3) ◽  
pp. 1934578X2110024
Author(s):  
Xin Chen ◽  
Yuanchun Ma ◽  
Xiongjun Mou ◽  
Hao Liu ◽  
Hao Ming ◽  
...  
Keyword(s):  
Animal Behavior ◽  
Neural Circuit ◽  
Concentration Level ◽  
Brain Regions ◽  
Mild Stress ◽  
Depression Effect ◽  
Monoamine Neurotransmitters ◽  
Reward Circuitry ◽  
High Doses ◽  
The Brain

Depression, a major worldwide mental disorder, leads to massive disability and can result in death. The PFC-NAc-VTA neuro circuit is related to emotional, neurovegetative, and cognitive functions, which emerge as a circuit-level framework for understanding reward deficits in depression. Neurotransmitters, which are widely distributed in different brain regions, are important detected targets for the evaluation of depression. Shuganheweitang (SGHWT) is a popular prescription in clinical therapy for depression. In order to investigate its possible pharmacodynamics and anti-depressive mechanism, the complex plant material was separated into different fractions. These in low and high doses, along with low and high doses of SGHWT were tested in animal behavior tests. The low and high doses of SGHWT were more effective than the various fractions, which indicate the importance of synergistic function in traditional Chinese medicine. Furthermore, amino acid (GABA, Glu) and monoamine neurotransmitters (DA, 5-HT, NA, 5-HIAA) in the PFC-NAc-VTA neuro circuit were investigated by UPLC-MS/MS. The level trend of DA and 5-HT were consistent in the PFC-NAc-VTA neuro circuit, whereas 5-HIAA was decreased in the PFC, Glu was decreased in the PFC and VTA, and NA and GABA were decreased in the NAc. The results indicate that the pathogenesis of depression is associated with dysfunction of the PFC-NAc-VTA neural circuit, mainly through the neural projection effects of neurotransmitters associated with various brain regions in the neural circuit. PCA and OPLS-DA score plots demonstrated the similarities of individuals within each group and the differences among the groups. In this study, SGHWT could regulate the concentration level of different neurotransmitters in the PFC-NAc-VTA neuro circuit to improve the depression, which benefitted from the recognition of the brain reward circuitry in mood disorders.

Beyond the Reward Pathway: Coding Reward Magnitude and Error in the Rat Subthalamic Nucleus

2009 ◽  
Vol 102 (4) ◽  
pp. 2526-2537 ◽  
Author(s):  
Sylvie Lardeux ◽  
Remy Pernaud ◽  
Dany Paleressompoulle ◽  
Christelle Baunez
Keyword(s):  
Subthalamic Nucleus ◽  
Firing Pattern ◽  
Sucrose Solution ◽  
Critical Role ◽  
The Other ◽  
Reward Circuitry ◽  
Reward Delivery ◽  
Reward Pathway ◽  
Subthalamic Neurons ◽  
The Brain

It was recently shown that subthalamic nucleus (STN) lesions affect motivation for food, cocaine, and alcohol, differentially, according to either the nature of the reward or the preference for it. The STN may thus code a reward according to its value. Here, we investigated how the firing of subthalamic neurons is modulated during expectation of a predicted reward between two possibilities (4 or 32% sucrose solution). The firing pattern of neurons responding to predictive cues and to reward delivery indicates that STN neurons can be divided into subpopulations responding specifically to one reward and less or giving no response to the other. In addition, some neurons (“oops” neurons) specifically encode errors as they respond only during error trials. These results reveal that the STN plays a critical role in ascertaining the value of the reward and seems to encode that value differently depending on the magnitude of the reward. These data highlight the importance of the STN in the reward circuitry of the brain.

scholarly journals Harmonic Brain Modes: A Unifying Framework for Linking Space and Time in Brain Dynamics

2017 ◽  
Vol 24 (3) ◽  
pp. 277-293 ◽  
Author(s):  
Selen Atasoy ◽  
Gustavo Deco ◽  
Morten L. Kringelbach ◽  
Joel Pearson
Keyword(s):  
Neural Activity ◽  
Brain Activity ◽  
Activity Patterns ◽  
Structural Connectivity ◽  
Building Blocks ◽  
Mental States ◽  
Brain Dynamics ◽  
Space And Time ◽  
Wide Range ◽  
The Brain

A fundamental characteristic of spontaneous brain activity is coherent oscillations covering a wide range of frequencies. Interestingly, these temporal oscillations are highly correlated among spatially distributed cortical areas forming structured correlation patterns known as the resting state networks, although the brain is never truly at “rest.” Here, we introduce the concept of harmonic brain modes—fundamental building blocks of complex spatiotemporal patterns of neural activity. We define these elementary harmonic brain modes as harmonic modes of structural connectivity; that is, connectome harmonics, yielding fully synchronous neural activity patterns with different frequency oscillations emerging on and constrained by the particular structure of the brain. Hence, this particular definition implicitly links the hitherto poorly understood dimensions of space and time in brain dynamics and its underlying anatomy. Further we show how harmonic brain modes can explain the relationship between neurophysiological, temporal, and network-level changes in the brain across different mental states ( wakefulness, sleep, anesthesia, psychedelic). Notably, when decoded as activation of connectome harmonics, spatial and temporal characteristics of neural activity naturally emerge from the interplay between excitation and inhibition and this critical relation fits the spatial, temporal, and neurophysiological changes associated with different mental states. Thus, the introduced framework of harmonic brain modes not only establishes a relation between the spatial structure of correlation patterns and temporal oscillations (linking space and time in brain dynamics), but also enables a new dimension of tools for understanding fundamental principles underlying brain dynamics in different states of consciousness.

Shape Memory Alloy Actuatable Woven Neural Probes

2018 ◽  
Author(s):  
Gabriella Shull ◽  
Jay Jia Hu ◽  
Justin Buschnyj ◽  
Henry Koon ◽  
Julianna Abel ◽  
...  
Keyword(s):  
Shape Memory Alloy ◽  
Shape Memory ◽  
Neural Activity ◽  
Inflammatory Responses ◽  
Neural Probes ◽  
Thermally Induced ◽  
Tissue Phantom ◽  
Computer Interfaces ◽  
Ordered Array ◽  
The Brain

The ability to sense neural activity using electrodes has allowed scientists to use this information to temporarily restore movement in paralyzed individuals using brain-computer interfaces (BCI). However, current electrodes do not provide chronic recording of the brain due to the inflammatory response of the immune system caused by the large (∼ 20–80 μm) size of the shanks, and the mechanical mismatch of the shanks relative to the brain. Electrode designs are evolving to use small (< 15 μm) flexible neural probes to minimize inflammatory responses and enable chronic use. However, their flexibility limits the scalability — it is challenging to assemble 3D arrays of such electrodes, to insert the arrays of flexible neural probes into the brain without buckling, and to uniformly distribute them into large areas of the brain. Thus, we created Shape Memory Alloy (SMA) actuated Woven Neural Probes (WNPs). A linear array of 32 flexible insulated microwires were interwoven with SMA wires resulting in an ordered array of parallel electrodes. SMA WNPs were shaped to an initial constricted profile for reliable insertion into a tissue phantom. Following insertion, the SMA wires were used as actuators to unravel the constricted WNP to distribute electrodes across large volumes. We demonstrated that the WNPs could be inserted into the brain without buckling and record neural activity. In separate experiments, we showed that the SMA could mechanically distribute the WNPs via thermally induced actuation. This work thus highlights the potential of actuatable WNPs to be used as a platform for neural recording.

scholarly journals Microglia, Cytokines, and Neural Activity: Unexpected Interactions in Brain Development and Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Austin Ferro ◽  
Yohan S. S. Auguste ◽  
Lucas Cheadle
Keyword(s):  
Brain Development ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Neural Activity ◽  
Signaling Molecules ◽  
Evolutionary Strategy ◽  
Inflammatory Signaling ◽  
Peripheral Tissues ◽  
And Function ◽  
The Brain

Intercellular signaling molecules such as cytokines and their receptors enable immune cells to communicate with one another and their surrounding microenvironments. Emerging evidence suggests that the same signaling pathways that regulate inflammatory responses to injury and disease outside of the brain also play powerful roles in brain development, plasticity, and function. These observations raise the question of how the same signaling molecules can play such distinct roles in peripheral tissues compared to the central nervous system, a system previously thought to be largely protected from inflammatory signaling. Here, we review evidence that the specialized roles of immune signaling molecules such as cytokines in the brain are to a large extent shaped by neural activity, a key feature of the brain that reflects active communication between neurons at synapses. We discuss the known mechanisms through which microglia, the resident immune cells of the brain, respond to increases and decreases in activity by engaging classical inflammatory signaling cascades to assemble, remodel, and eliminate synapses across the lifespan. We integrate evidence from (1) in vivo imaging studies of microglia-neuron interactions, (2) developmental studies across multiple neural circuits, and (3) molecular studies of activity-dependent gene expression in microglia and neurons to highlight the specific roles of activity in defining immune pathway function in the brain. Given that the repurposing of signaling pathways across different tissues may be an important evolutionary strategy to overcome the limited size of the genome, understanding how cytokine function is established and maintained in the brain could lead to key insights into neurological health and disease.

scholarly journals Robust and distributed neural representation of action values

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Eun Ju Shin ◽  
Yunsil Jang ◽  
Soyoun Kim ◽  
Hoseok Kim ◽  
Xinying Cai ◽  
...  
Keyword(s):  
Neural Activity ◽  
Statistical Tests ◽  
Brain Structures ◽  
Surrogate Data ◽  
Neural Representation ◽  
Decision Variables ◽  
Multiple Regions ◽  
Serial Correlations ◽  
Action Value ◽  
The Brain

Studies in rats, monkeys, and humans have found action-value signals in multiple regions of the brain. These findings suggest that action-value signals encoded in these brain structures bias choices toward higher expected rewards. However, previous estimates of action-value signals might have been inflated by serial correlations in neural activity and also by activity related to other decision variables. Here, we applied several statistical tests based on permutation and surrogate data to analyze neural activity recorded from the striatum, frontal cortex, and hippocampus. The results show that previously identified action-value signals in these brain areas cannot be entirely accounted for by concurrent serial correlations in neural activity and action value. We also found that neural activity related to action value is intermixed with signals related to other decision variables. Our findings provide strong evidence for broadly distributed neural signals related to action value throughout the brain.

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