scholarly journals A circadian output circuit controls sleep-wake arousal threshold in Drosophila

2018 ◽  
Author(s):  
Fang Guo ◽  
Meghana Holla ◽  
Madelen M. Díaz ◽  
Michael Rosbash
Keyword(s):  
Brain Regions ◽  
Central Complex ◽  
Discrete Subset ◽  
Vision Navigation ◽  
Arousal Threshold ◽  
Ellipsoid Body ◽  
Wake Patterns ◽  
Circadian Pacemakers ◽  
Diurnal Sleep

SummaryThe Drosophila core circadian circuit contains distinct groups of interacting neurons that give rise to diurnal sleep-wake patterns. Previous work showed that a subset of Dorsal Neurons 1 (DN1s) are sleep-promoting through their inhibition of activity-promoting circadian pacemakers. Here we show that these anterior-projecting DNs (APDNs) also “exit” the circadian circuitry and communicate with the homeostatic sleep center in higher brain regions to regulate sleep and sleep-wake arousal threshold. These APDNs connect to a small discrete subset of tubercular-bulbar neurons, which are connected in turn to specific sleep-centric Ellipsoid Body (EB)-Ring neurons of the central complex. Remarkably, activation of the APDNs produces sleep-like oscillations in the EB and also raises the arousal threshold, which requires neurotransmission throughout the circuit. The data indicate that this APDN-TuBusup-EB circuit temporally regulates sleep-wake arousal threshold in addition to the previously defined role of the TuBu-EB circuit in vision, navigation and attention.

scholarly journals The G Protein-Coupled Glutamate Receptors as Novel Molecular Targets in Schizophrenia Treatment—A Narrative Review

2021 ◽  
Vol 10 (7) ◽  
pp. 1475
Author(s):  
Waldemar Kryszkowski ◽  
Tomasz Boczek
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Glutamate Release ◽  
Molecular Targets ◽  
Brain Regions ◽  
Psychotic Symptoms ◽  
Unknown Etiology ◽  
Metabotropic Glutamate ◽  
G Protein Coupled

Schizophrenia is a severe neuropsychiatric disease with an unknown etiology. The research into the neurobiology of this disease led to several models aimed at explaining the link between perturbations in brain function and the manifestation of psychotic symptoms. The glutamatergic hypothesis postulates that disrupted glutamate neurotransmission may mediate cognitive and psychosocial impairments by affecting the connections between the cortex and the thalamus. In this regard, the greatest attention has been given to ionotropic NMDA receptor hypofunction. However, converging data indicates metabotropic glutamate receptors as crucial for cognitive and psychomotor function. The distribution of these receptors in the brain regions related to schizophrenia and their regulatory role in glutamate release make them promising molecular targets for novel antipsychotics. This article reviews the progress in the research on the role of metabotropic glutamate receptors in schizophrenia etiopathology.

scholarly journals The Protective Role of Brain CYP2J in Parkinson’s Disease Models

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yueran Li ◽  
Jinhua Wu ◽  
Xuming Yu ◽  
Shufang Na ◽  
Ke Li ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Regions ◽  
Protective Role ◽  
Neural Cells ◽  
Endogenous Substrates ◽  
6 Hydroxydopamine ◽  
Myd88 Signaling ◽  
Lps Treatment

CYP2J proteins are present in the neural cells of human and rodent brain regions. The aim of this study was to investigate the role of brain CYP2J in Parkinson’s disease. Rats received right unilateral injection with lipopolysaccharide (LPS) or 6-hydroxydopamine (6-OHDA) in the substantia nigra following transfection with or without the CYP2J3 expression vector. Compared with LPS-treated rats, CYP2J3 transfection significantly decreased apomorphine-induced rotation by 57.3% at day 12 and 47.0% at day 21 after LPS treatment; moreover, CYP2J3 transfection attenuated the accumulation of α-synuclein. Compared with the 6-OHDA group, the number of rotations by rats transfected with CYP2J3 decreased by 59.6% at day 12 and 43.5% at day 21 after 6-OHDA treatment. The loss of dopaminergic neurons and the inhibition of the antioxidative system induced by LPS or 6-OHDA were attenuated following CYP2J3 transfection. The TLR4-MyD88 signaling pathway was involved in the downregulation of brain CYP2J induced by LPS, and CYP2J transfection upregulated the expression of Nrf2 via the inhibition of miR-340 in U251 cells. The data suggest that increased levels of CYP2J in the brain can delay the pathological progression of PD initiated by inflammation or neurotoxins. The alteration of the metabolism of the endogenous substrates (e.g., AA) could affect the risk of neurodegenerative disease.

Electroencephalographic Recordings of Focal Seizures in Patients Affected by Periventricular Nodular Heterotopia: Role of the Heterotopic Nodules in the Genesis of Epileptic Discharges

2004 ◽  
Vol 19 (3) ◽  
pp. 369-377
Author(s):  
Giorgio Battaglia ◽  
Silvana Franceschetti ◽  
Luisa Chiapparini ◽  
Elena Freri ◽  
Stefania Bassanini ◽  
...  
Keyword(s):  
Brain Regions ◽  
Periventricular Nodular Heterotopia ◽  
Focal Seizures ◽  
Ictal Eeg ◽  
Epileptic Discharges ◽  
Nodular Heterotopia ◽  
Eeg Recordings ◽  
Drug Resistant Epilepsy ◽  
Video Eeg

Patients affected by periventricular nodular heterotopia are frequently characterized by focal drug-resistant epilepsy. To investigate the role of periventricular nodules in the genesis of seizures, we analyzed the electroencephalographic (EEG) features of focal seizures recorded by means of video-EEG in 10 patients affected by different types of periventricular nodular heterotopia and followed for prolonged periods of time at the epilepsy center of our institute. The ictal EEG recordings with surface electrodes revealed common features in all patients: all seizures originated from the brain regions where the periventricular nodular heterotopia were located; EEG patterns recorded on the leads exploring the periventricular nodular heterotopia were very similar both at the onset and immediately after the seizure's end in all patients. Our data suggest that seizures are generated by abnormal anatomic circuitries, including the heterotopic nodules and adjacent cortical areas. The major role of heterotopic neurons in the genesis and propagation of epileptic discharges must be taken into account when planning surgery for epilepsy in patients with periventricular nodular heterotopia. ( J Child Neurol 2005;20:369—377).

scholarly journals Activity in the brain’s valuation and mentalizing networks is associated with propagation of online recommendations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elisa C. Baek ◽  
Matthew Brook O’Donnell ◽  
Christin Scholz ◽  
Rui Pei ◽  
Javier O. Garcia ◽  
...  
Keyword(s):  
Social Media ◽  
Word Of Mouth ◽  
Mental States ◽  
Brain Regions ◽  
Prior Work ◽  
Opinion Change ◽  
Wide Range ◽  
The Mind ◽  
Mentalizing System

AbstractWord of mouth recommendations influence a wide range of choices and behaviors. What takes place in the mind of recommendation receivers that determines whether they will be successfully influenced? Prior work suggests that brain systems implicated in assessing the value of stimuli (i.e., subjective valuation) and understanding others’ mental states (i.e., mentalizing) play key roles. The current study used neuroimaging and natural language classifiers to extend these findings in a naturalistic context and tested the extent to which the two systems work together or independently in responding to social influence. First, we show that in response to text-based social media recommendations, activity in both the brain’s valuation system and mentalizing system was associated with greater likelihood of opinion change. Second, participants were more likely to update their opinions in response to negative, compared to positive, recommendations, with activity in the mentalizing system scaling with the negativity of the recommendations. Third, decreased functional connectivity between valuation and mentalizing systems was associated with opinion change. Results highlight the role of brain regions involved in mentalizing and positive valuation in recommendation propagation, and further show that mentalizing may be particularly key in processing negative recommendations, whereas the valuation system is relevant in evaluating both positive and negative recommendations.

scholarly journals Possible Clues for Brain Energy Translation via Endolysosomal Trafficking of APP-CTFs in Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Senthilkumar Sivanesan ◽  
Ravi Mundugaru ◽  
Jayakumar Rajadas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ketone Bodies ◽  
Brain Regions ◽  
Pentose Phosphate ◽  
Lactate Shuttle ◽  
Carboxy Terminal ◽  
Brain Energy

Vascular dysfunctions, hypometabolism, and insulin resistance are high and early risk factors for Alzheimer’s disease (AD), a leading neurological disease associated with memory decline and cognitive dysfunctions. Early defects in glucose transporters and glycolysis occur during the course of AD progression. Hypometabolism begins well before the onset of early AD symptoms; this timing implicates the vulnerability of hypometabolic brain regions to beta-secretase 1 (BACE-1) upregulation, oxidative stress, inflammation, synaptic failure, and cell death. Despite the fact that ketone bodies, astrocyte-neuron lactate shuttle, pentose phosphate pathway (PPP), and glycogenolysis compensate to provide energy to the starving AD brain, a considerable energy crisis still persists and increases during disease progression. Studies that track brain energy metabolism in humans, animal models of AD, and in vitro studies reveal striking upregulation of beta-amyloid precursor protein (β-APP) and carboxy-terminal fragments (CTFs). Currently, the precise role of CTFs is unclear, but evidence supports increased endosomal-lysosomal trafficking of β-APP and CTFs through autophagy through a vague mechanism. While intracellular accumulation of Aβ is attributed as both the cause and consequence of a defective endolysosomal-autophagic system, much remains to be explored about the other β-APP cleavage products. Many recent works report altered amino acid catabolism and expression of several urea cycle enzymes in AD brains, but the precise cause for this dysregulation is not fully explained. In this paper, we try to connect the role of CTFs in the energy translation process in AD brain based on recent findings.

scholarly journals Dissociable oscillatory networks support gain and loss processing in human orbitofrontal cortex

2021 ◽  
Author(s):  
Ignacio Saez ◽  
Jack Lin ◽  
Edward Chang ◽  
Josef Parvizi ◽  
Robert T. Knight ◽  
...  
Keyword(s):  
Neural Activity ◽  
Orbitofrontal Cortex ◽  
Low Frequency ◽  
Brain Regions ◽  
Reward Processing ◽  
Neural Oscillations ◽  
Beta Band ◽  
Neuronal Ensembles ◽  
Gain And Loss

AbstractHuman neuroimaging and animal studies have linked neural activity in orbitofrontal cortex (OFC) to valuation of positive and negative outcomes. Additional evidence shows that neural oscillations, representing the coordinated activity of neuronal ensembles, support information processing in both animal and human prefrontal regions. However, the role of OFC neural oscillations in reward-processing in humans remains unknown, partly due to the difficulty of recording oscillatory neural activity from deep brain regions. Here, we examined the role of OFC neural oscillations (<30Hz) in reward processing by combining intracranial OFC recordings with a gambling task in which patients made economic decisions under uncertainty. Our results show that power in different oscillatory bands are associated with distinct components of reward evaluation. Specifically, we observed a double dissociation, with a selective theta band oscillation increase in response to monetary gains and a beta band increase in response to losses. These effects were interleaved across OFC in overlapping networks and were accompanied by increases in oscillatory coherence between OFC electrode sites in theta and beta band during gain and loss processing, respectively. These results provide evidence that gain and loss processing in human OFC are supported by distinct low-frequency oscillations in networks, and provide evidence that participating neuronal ensembles are organized functionally through oscillatory coherence, rather than local anatomical segregation.

scholarly journals Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels

2021 ◽  
Vol 14 ◽  
Author(s):  
Deepanjali Dwivedi ◽  
Upinder S. Bhalla
Keyword(s):  
Ion Channels ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Brain Regions ◽  
Channel Activity ◽  
Current Review ◽  
Cellular Excitability ◽  
M Channels ◽  
Neuronal Functions

SK, HCN, and M channels are medium afterhyperpolarization (mAHP)-mediating ion channels. The three channels co-express in various brain regions, and their collective action strongly influences cellular excitability. However, significant diversity exists in the expression of channel isoforms in distinct brain regions and various subcellular compartments, which contributes to an equally diverse set of specific neuronal functions. The current review emphasizes the collective behavior of the three classes of mAHP channels and discusses how these channels function together although they play specialized roles. We discuss the biophysical properties of these channels, signaling pathways that influence the activity of the three mAHP channels, various chemical modulators that alter channel activity and their therapeutic potential in treating various neurological anomalies. Additionally, we discuss the role of mAHP channels in the pathophysiology of various neurological diseases and how their modulation can alleviate some of the symptoms.

scholarly journals AMPed-up adolescents: the role of age in the abuse of amphetamines and its consequences on cognition and prefrontal cortex development

2020 ◽  
Author(s):  
Sara Ruth Westbrook ◽  
Lauren Carrica ◽  
Asia Banks ◽  
Joshua Michael Gulley
Keyword(s):  
Prefrontal Cortex ◽  
Animal Studies ◽  
Drug Effects ◽  
Epidemiological Studies ◽  
Brain Regions ◽  
Vulnerability Factors ◽  
Brain And Behavior ◽  
And Behavior ◽  
Detrimental Impact

Adolescent use of amphetamine and its closely related, methylated version methamphetamine, is alarmingly high in those who use drugs for nonmedical purposes. This raises serious concerns about the potential for this drug use to have a long-lasting, detrimental impact on the normal development of the brain and behavior that is ongoing during adolescence. In this review, we explore recent findings from both human and laboratory animal studies that investigate the consequences of amphetamine and methamphetamine exposure during this stage of life. We highlight studies that assess sex differences in adolescence, as well as those that are designed specifically to address the potential unique effects of adolescent exposure by including groups at other life stages (typically young adulthood). We consider epidemiological studies on age and sex as vulnerability factors for developing problems with the use of amphetamines, as well as human and animal laboratory studies that tap into age differences in use, its short-term effects on behavior, and the long-lasting consequences of this exposure on cognition. We also focus on studies of drug effects in the prefrontal cortex, which is known to be critically important for cognition and is among the later maturing brain regions. Finally, we discuss important issues that should be addressed in future studies so that the field can further our understanding of the mechanisms underlying adolescent use of amphetamines and its outcomes on the developing brain and behavior.

scholarly journals Somatic mutations in Parkinson disease are enriched in synaptic and neuronal processes

2020 ◽  
Author(s):  
Irene Lobon ◽  
Manuel Solis-Moruno ◽  
David Juan ◽  
Ashraf Muhaisen ◽  
Federico Abascal ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Somatic Mutations ◽  
Amplicon Sequencing ◽  
Brain Regions ◽  
Single Nucleotide Variants ◽  
Validation Rate ◽  
Synaptic Functions ◽  
Whole Exome ◽  
Neuronal Processes

The role of somatic mutations in complex diseases, including neurodevelopmental and neurodegenerative disorders, is becoming increasingly clear. To explore their relevance in sporadic Parkinson disease, we performed whole-exome sequencing in blood and four brain regions of ten patients. We identified 59 candidate somatic single nucleotide variants (sSNVs) through sensitive calling and extensive filtering. We validated 27 of them with amplicon-based deep sequencing, with a 70% validation rate for the highest-confidence variants. Most of the sSNVs were exclusively called in blood but were also found in the brain tissues with the ultra-deep amplicon sequencing, demonstrating the strength of multi-tissue sampling designs. We could confirm between 0 and 6 sSNVs per patient and generally those with a shorter lifespan carried more variants. Remarkably, the validated sSNVs are enriched in genes with synaptic functions that are co-expressed with genes previously associated with Parkinson disease.

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