Serotonin

Why do dorsal raphe serotonin neurons respond to reward, surprise, salience and uncertainty in ways that resist a single explanation? This talk proposes that serotonin activity encodes prospective value: a prediction of cumulative future reward. The model is motivated by the unusually strong and persistent spike-frequency adaptation of these neurons, which may support efficient and accurate predictions. It reproduces important qualitative features of serotonergic responses that earlier models miss and predicts measured in vivo firing rates more accurately than competing accounts. By treating p

…that dorsal raphe (DR) derived serotonin (5HT) controls visual attention. We adopted a behavioral model that captured how mice allocated attention to cued and uncued visual features. Simultaneous photometry recordings showed that DR activity decreas

…a scalar reward prediction error, the serotonin system’s function has been difficult to elucidate, partly due to the heterogeneity of its individual neuronal responses [1]. Although serotonergic neurons are known to respond to various salient events [2] and rewards [3], which can be accounted for by ad-hoc extensions to a reinforcement learning framework, our study presents the first comprehensive, normative framewor

Wearable sensors that detect and quantify biomarkers in retrievable biofluids (e.g., interstitial fluid, sweat, tears) provide information on human dynamic physiological and psychological states. This information can transform health and wellness by providing actionable feedback. Due to outdated and insufficiently sensitive technologies, current on-body sensing systems have capabilities limited to pH, and a few high-concentration electrolytes, metabolites, and nutrients. As such, wearable sensing systems cannot detect key low-concentration biomarkers indicative of stress, inflammation, metabo

【Aims】Epilepsy, a recurrent neurological disease with abnormal neurotransmitter kinetics in the brain, has emerged as a global health concern. The mechanism of epileptic seizures is thought to involve a relative imbalance between excitatory and inhibitory neurotransmitters. Despite the recent advances in clinical and basic research on the pathogenesis of epilepsy, the complex relationship between the neurotransmitter dynamics and behavior with and without antiepileptic drugs (AEDs) during seizures remains unclear. We aimed to investigate the dynamics of neurotransmitters during convulsive seiz

…In the serotonin (5-HT) system alpha-synuclein (a-Syn) aggregates are present and functional changes are involved in the PD prodromal phase and contribute to non-motor symptoms​. Using a mouse model of depression and synucleinopathy in raphe 5-HT neurons, we aim to evaluate: 1- behavioral phenotype, 2- synaptic changes in prefrontal cortex and striatum, and 3- possible sex-based differences. METHODS: Recombinant adeno-associated viral vectors (AAV2/5) encoding wild-type human a-Syn (h-a-Syn) were infused in r

Internal states and behavior are associated with brain-wide changes in the activity of neuronal circuits. Such global shifts are believed to be implemented by changes in neuromodulatory tone. Neuromodulators originate from a few neurons and are released widely throughout the brain to alter the function of target circuits.The amygdala plays an essential role in the processing of emotional stimuli. Salience and synaptic alterations in this region are critical for emotional processing and learning. The amygdala is innervated by all major neuromodulators, yet we know little about the dynamics of n

Neuromodulatory systems, more specifically dopamine, noradrenaline, serotonin, and acetylcholine can dynamically change brain states and rapidly alter information processing of large number of neurons. Therefore, they can play a crucial role in cognitive functions, including learning and memory, and are accordingly severely implicated in neurodegenerative diseases. Interestingly, neuromodulatory systems often regulate seemingly overlapping cognitive processes and show similar modes of action. To reveal possible synergistic or antagonistic relations and to better understand the exact role of th

The splicing factor RBFOX1 exerts a pleiotropic effect on numerous psychiatric and neurodevelopmental disorders; however, the exact working mechanisms remain largely unknown. One potential mechanism that could partially explain the influence of RBFOX1 on some psychiatric traits is through the modulation of the serotonergic system, a common target for medical intervention in psychiatric disorders associated with RBFOX1.Here we studied a rbfox1 mutant zebrafish model, carrying a rbfox1sa15940 allele that expresses a shorter, aberrant rbfox1 mRNA. In the homozygous rbfox1sa15940 zebrafish we obse

…A dysfunctional serotonin (5-HT) system is generally considered a risk factor for depression. We propose the ventromedial prefrontal cortex (vmPFC)-dorsal raphe nucleus (DR) circuit as the key player underlying depressive/anxious disorders in PD, by virtue of its reciprocal connectivity. Female mice overe

…(NA) in the locus coeruleus (LC) and serotonin (5HT3) in the raphe nuclei (RN). For this purpose, male Wistar rats were used, t

…of pharmacologically selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy, persistent symptoms are reported in 40-60% of patients. Hence, we aim to analyze the levels of specific miRNAs and comprehensively evaluate the levels of serotonin, a pivotal neurotransmitter in the context of OCD. In the present study, blood serum was taken from peripheral whole blood s

This study aims to evaluate the contribution of extraembryonic sources of serotonin to prefrontal cortex (PFC) development and understand the placental role and mechanisms of serotonin supplementation to the foetus. To this end, we used mice deficient in serotonin production (TPH1 and TPH2 KO) and serotonin transporters (SERT and OCT3 KO). We assessed serotonin levels in placenta and embryonic brain during different phases of prenatal neurodevelopment using HPLC and immunohistochemistry. Furthermore, we evaluated the PFC maturation and serotonergic wiring by 3D brain ECi imaging in these mice.

…the potential interplay between the serotonin receptors 5-HT1A and 5-HT2C, which play a significant role in the pathology of depression. Experiments were performe

Dysregulation of serotonin (5-HT) transmission has been implicated as a factor in the development of depression. This study determined the effects of Tat on serotonin transporter (SERT), dynamic 5-HT release, and the effect of induction of Tat expression on mobility in the tail-suspension test (TST) in inducible Tat transgenic (iTat-tg) mice. Optimization of recombinant Tat1-86 (rTat1-86) concentration revealed a Ki of 7.2 nM for it inhibiting 5-HT uptake into mouse synaptosomes. SRI-32743 displayed a partial antagonism with 13 nM affinity and 69.5% Emax for inhibiting 5-HT uptake in CHO cells

…Research has found that serotonin plays a crucial role in the neuroplastic processes required for brain reorganisation after a stroke. We investigated whether modulation of serotonergic transmission of the dorsal raphe nucleus (DRN), together with rehabilitation training, leads to an improvement in motor recovery.In a photothrombotic stroke mouse model, lesion volume and localization were assessed following 24h after ischemia with 7T-MRI. We chemogenetically activated or inhibited the DRN through adeno-associated virus (AAV)

The application of biotin ligase or peroxidase fused with specific proteins or subcellular regions, combined with mass spectrometry-based quantitative proteomics, has become a potent approach for unravelling molecular interactions and determining the locations of native proteins based on their proximity. Recent applications of proximity-dependent biotinylation in neuroscience have yielded insights into the composition of sub-synaptic structures, including the synaptic cleft [1].Despite the effectiveness of proximity labelling methods in providing a global perspective on protein-protein interac

…(ACh), norepinephrine (NE) and serotonin (5-HT) in associative learning and the correlation of their release with the reward prediction error (RPE). To address this, we trained mice on a sound detection Pavlovian conditioning task with a 50% reward schedule that allowed examining clean representations of postivite (rewarded trials) and negative RPE (reward omission trials), while we measured DA, ACh, NE and 5-HT release by fiber photometry. Behavioral updating of value representations based on the outcome of the previous trial wa

The urocortin 1 (UCN1)-expressing neurons of the centrally projecting Edinger-Westphal nucleus (EWcp) are affected by the circadian rhythm, hormonal changes, stress and pain that are known to trigger migraine. Here we aimed at investigating the possible role of EWcp in migraine neurobiology.RNAscope in situ hybridization (ISH) combined with immunostaining was used to examine the expression of calcitonin gene-related peptide (CGRP) receptor component (Crcp) in both mouse and human EWcp and dorsal raphe nucleus (DRN). Anterograde and retrograde tracing study investigated the neuroanatomical conn

…and its ‘malfunction’ is shared across serotonin (5-HT)-related neuropsychiatric disorders and often find its origins during development. Proper cortical development is directed by a sequence of intrinsic ( transcription factors, local placental-derived 5-HT) and extrinsic (instructing 5-HT and catecholaminergic afferents) events. Recently, our group has shown a functional interplay between the 5-HT and catecholaminergic prefrontal projection systems during development leading to a distortion in PFC cytoarchitecture. Lack o

…Serotonin has been associated with MDD as a promising factor for over 60 years. However, serotonergic dynamics have only recently been linked to corticolimbic network activity. We aim to investigate the effect of serotonin on corticolimbic network activity, specifically in the media

…can be modulated by increasing serotonin levels by administering selective serotonin reuptake inhibitors (SSRI). However, little is known about the mechanistic background, especially the contribution of intracortical inhibition and facilitation, which depend on gamma-aminobutyric acid (GABA) and glutamate. We aimed to explore the relevance of drivers of plasticity (glutamate- and GABA-dependent processes) for the effects of serotonin enhancement on tDCS-induced plasticity in healthy humans. A crossover, partially double-bli

Maternal care is a crucial aspect of mammalian behavior. Mothers detect signals from their pups, perform specific behaviors essential to their care (nest preparation, nursing, keeping pups warm), and remain motivated to care for them despite danger or fear. These behaviors are well documented in mothers but are also observed in nulliparous rodents, though with notable differences in expression and initiation compared to experienced mothers. This study concentrates on maternal motivation and explores the distinct neuronal mechanisms impacted in dams and nulliparous females. Initially, our findi

Complex interactions between serotonin (5-hydroxytriptamine) and orexin (hypocretin) systems in the CNS modulate diverse physiological processes, including mood regulation, energy homeostasis, and spontaneous physical activity. A portion of this interaction may be explained by G protein-coupled receptor oligomerization, which might influence agonist affinity, efficacy, trafficking, and signal transduction. Orexin receptor 1 (OX1) and 5-hydroxytriptamine 2C receptor (5-HT2C) co-express in diverse neuronal populations and are involved in pathological conditions such as anxiety and eating disorde