scholarly journals Serotonergic neurons signal reward and punishment on multiple timescales

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Jeremiah Y Cohen ◽  
Mackenzie W Amoroso ◽  
Naoshige Uchida
Keyword(s):  
Dopaminergic Neurons ◽  
Large Fraction ◽  
Neuron Activity ◽  
Serotonergic Neuron ◽  
Serotonergic Neurons ◽  
Tonic Firing ◽  
Multiple Timescales ◽  
Firing Rates ◽  
The Brain ◽  
Reward And Punishment

Serotonin's function in the brain is unclear. One challenge in testing the numerous hypotheses about serotonin's function has been observing the activity of identified serotonergic neurons in animals engaged in behavioral tasks. We recorded the activity of dorsal raphe neurons while mice experienced a task in which rewards and punishments varied across blocks of trials. We ‘tagged’ serotonergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to light. We found three main features of serotonergic neuron activity: (1) a large fraction of serotonergic neurons modulated their tonic firing rates over the course of minutes during reward vs punishment blocks; (2) most were phasically excited by punishments; and (3) a subset was phasically excited by reward-predicting cues. By contrast, dopaminergic neurons did not show firing rate changes across blocks of trials. These results suggest that serotonergic neurons signal information about reward and punishment on multiple timescales.

scholarly journals Nonexocytotic serotonin release tonically suppresses serotonergic neuron activity

2015 ◽  
Vol 145 (3) ◽  
pp. 225-251 ◽  
Author(s):  
Boris Mlinar ◽  
Alberto Montalbano ◽  
Gilda Baccini ◽  
Francesca Tatini ◽  
Rolando Berlinguer Palmini ◽  
...  
Keyword(s):  
Serotonin Release ◽  
Raphe Nuclei ◽  
Neuron Activity ◽  
Release Mechanism ◽  
Serotonergic Neuron ◽  
Firing Activity ◽  
Serotonergic Neurons ◽  
Simple Diffusion ◽  
Inwardly Rectifying Potassium Channels ◽  
Raphé Nuclei

The firing activity of serotonergic neurons in raphe nuclei is regulated by negative feedback exerted by extracellular serotonin (5-HT)o acting through somatodendritic 5-HT1A autoreceptors. The steady-state [5-HT]o, sensed by 5-HT1A autoreceptors, is determined by the balance between the rates of 5-HT release and reuptake. Although it is well established that reuptake of 5-HTo is mediated by 5-HT transporters (SERT), the release mechanism has remained unclear. It is also unclear how selective 5-HT reuptake inhibitor (SSRI) antidepressants increase the [5-HT]o in raphe nuclei and suppress serotonergic neuron activity, thereby potentially diminishing their own therapeutic effect. Using an electrophysiological approach in a slice preparation, we show that, in the dorsal raphe nucleus (DRN), continuous nonexocytotic 5-HT release is responsible for suppression of phenylephrine-facilitated serotonergic neuron firing under basal conditions as well as for autoinhibition induced by SSRI application. By using 5-HT1A autoreceptor-activated G protein–gated inwardly rectifying potassium channels of patched serotonergic neurons as 5-HTo sensors, we show substantial nonexocytotic 5-HT release under conditions of abolished firing activity, Ca2+ influx, vesicular monoamine transporter 2–mediated vesicular accumulation of 5-HT, and SERT-mediated 5-HT transport. Our results reveal a cytosolic origin of 5-HTo in the DRN and suggest that 5-HTo may be supplied by simple diffusion across the plasma membrane, primarily from the dense network of neurites of serotonergic neurons surrounding the cell bodies. These findings indicate that the serotonergic system does not function as a sum of independently acting neurons but as a highly interdependent neuronal network, characterized by a shared neurotransmitter pool and the regulation of firing activity by an interneuronal, yet activity-independent, nonexocytotic mechanism.

Comparison of Cytocidal Activities of L-DOPA and Dopamine in S. cerevisiae and C. glabrata

2020 ◽  
Vol 16 (1) ◽  
pp. 90-93
Author(s):  
Carmen E. Iriarte ◽  
Ian G. Macreadie
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Candida Glabrata ◽  
High Sensitivity ◽  
Time Dependent ◽  
Colony Forming Units ◽  
Dependent Cell ◽  
The Brain

Background: Parkinson's Disease results from a loss of dopaminergic neurons, and reduced levels of the neurotransmitter dopamine. Parkinson's Disease treatments involve increasing dopamine levels through administration of L-DOPA, which can cross the blood brain barrier and be converted to dopamine in the brain. The toxicity of dopamine has previously studied but there has been little study of L-DOPA toxicity. Methods: We have compared the toxicity of dopamine and L-DOPA in the yeasts, Saccharomyces cerevisiae and Candida glabrata by cell viability assays, measuring colony forming units. Results: L-DOPA and dopamine caused time-dependent cell killing in Candida glabrata while only dopamine caused such effects in Saccharomyces cerevisiae. The toxicity of L-DOPA is much lower than dopamine. Conclusion: Candida glabrata exhibits high sensitivity to L-DOPA and may have advantages for studying the cytotoxicity of L-DOPA.

scholarly journals Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (3) ◽  
pp. 1059
Author(s):  
Bodo C. Melnik
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Dopaminergic Neurons ◽  
Vagal Nerve ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
The Brain

Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D.

scholarly journals Importance of Nanoparticles for the Delivery of Antiparkinsonian Drugs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 508
Author(s):  
Sara Silva ◽  
António J. Almeida ◽  
Nuno Vale
Keyword(s):  
Side Effects ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Pharmacokinetic Profile ◽  
The Elderly ◽  
Motor Symptoms ◽  
Administration Routes ◽  
Pharmaceutical Therapy ◽  
Drug Pharmacokinetic ◽  
The Brain

Parkinson’s disease (PD) affects around ten million people worldwide and is considered the second most prevalent neurodegenerative disease after Alzheimer’s disease. In addition, there is a higher risk incidence in the elderly population. The main PD hallmarks include the loss of dopaminergic neurons and the development of Lewy bodies. Unfortunately, motor symptoms only start to appear when around 50–70% of dopaminergic neurons have already been lost. This particularly poses a huge challenge for early diagnosis and therapeutic effectiveness. Actually, pharmaceutical therapy is able to relief motor symptoms, but as the disease progresses motor complications and severe side-effects start to appear. In this review, we explore the research conducted so far in order to repurpose drugs for PD with the use of nanodelivery systems, alternative administration routes, and nanotheranostics. Overall, studies have demonstrated great potential for these nanosystems to target the brain, improve drug pharmacokinetic profile, and decrease side-effects.

Finite Difference Time Domain Simulations of Hybrid Neurotransducers Based Optical Microlasers

2020 ◽  
Author(s):  
Maurizio Manzo ◽  
Omar Cavazos
Keyword(s):  
Finite Difference ◽  
Chronic Traumatic Encephalopathy ◽  
Numerical Technique ◽  
Well Being ◽  
Infrared Light ◽  
Neuron Activity ◽  
Living Matter ◽  
Brain Functions ◽  
Laser Modes ◽  
The Brain

Abstract Different pathologies such as Alzheimer’s, Parkinson’s, Wilson’s diseases, and chronic traumatic encephalopathy due to blasts and impacts affect the brain functions altering the neuronal electrical activity. An important aspect of the brain study is the use of non-invasive, non-surgical methodologies that are suitable to the well-being of the patients. Only a portion of the electromagnetic field can be detected by applying sensors outside the scalp; in addition, surgery is often involved if sensors are applied in the subcutaneous region of the skull. Optical techniques applied to biomedical research and diagnostics have been spread during the last decades. For example, near infrared light (NIR) of spectral range goes from 800 nm to 1300 nm, it is harmless radiation for the living tissue, and can penetrate the living matter in depth as, it turns out that most of the living matter is transparent to the NIR light. Optical microlasers have been recently proposed as neurotransducers for minimally invasive neuron activity detection for the next generation of brain-computer interface (BCI) systems. They are lightweight, require low power consumption and exhibit low latency. This novel sensor that can be made of biocompatible material is coupled with a voltage sensitive dye; the fluorescence of the dye, which is excited by an external light source, is used to generate optical (laser) modes. Any variation in the neurons’ membrane electric potential via evanescent field’s perturbation turn affect the shifting of these laser modes. In order to reduce the energy required to power these devices and to improve their optical emission, metal nanoparticles can be coupled in order to use their plasmonic effect. In this paper, finite-difference timedomain (FDTD) numerical technique is used to analyze the performances on a dye-doped microlaser. Purcell effect and resonant wavelengths are observed.

A bimodal probe for fluorescence and synchrotron X-ray fluorescence imaging of dopaminergic neurons in brain

2022 ◽  
Author(s):  
Meiling Yan ◽  
Tingting Zuo ◽  
Jichao Zhang ◽  
Yiyang Wang ◽  
Ying Zhu ◽  
...  
Keyword(s):  
Fluorescence Imaging ◽  
Immunoglobulin G ◽  
Dopaminergic Neurons ◽  
X Ray ◽  
Erythrosine B ◽  
The Brain

A bimodal probe, erythrosine B (EB) conjugated immunoglobulin G complex (EB/IgG), has been developed for fluorescence and synchrotron X-ray fluorescence (SXRF) imaging of dopaminergic neurons in the brain.

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