serotonergic

Neuromodulation of subjective experience

Many psychoactive substances are used with the aim of altering experience, e.g. as analgesics, antidepressants or antipsychotics. These drugs act on specific receptor systems in the brain, including the opioid, serotonergic and dopaminergic systems. In this talk, I will summarise human drug studies targeting opioid receptors and their role for human experience, with focus on the experience of pain, stress, mood, and social connection. Opioids are only indicated for analgesia, due to their potential to cause addiction. When these regulations occurred, other known effects were relegated to side effects. This may be the cause of the prevalent myth that opioids are the most potent painkillers, despite evidence from head-to-head trials, Cochrane reviews and network meta-analyses that opioids are not superior to non-opioid analgesics in the treatment of acute or chronic non-cancer pain. However, due to the variability and diversity of opioid effects across contexts and experiences, some people under some circumstances may indeed benefit from prolonged treatment. I will present data on individual differences in opioid effects due to participant sex and stress induction. Understanding the effects of these commonly used medications on other aspects of the human experience is important to ensure correct use and to prevent unnecessary pain and addiction risk.

Hunger state-dependent modulation of decision-making in larval Drosophila

It is critical for all animals to make appropriate, but also flexible, foraging decisions, especially when facing starvation. Sensing olfactory information is essential to evaluate food quality before ingestion. Previously, we found that <i>Drosophila</i> larvae switch their response to certain odors from aversion to attraction when food deprived. The neural mechanism underlying this switch in behavior involves serotonergic modulation and reconfiguration of odor processing in the early olfactory sensory system. We now investigate if a change in hunger state also influences other behavioral decisions. Since it had been shown that fly larvae can perform cannibalism, we investigate the effect of food deprivation on feeding on dead conspecifics. We find that fed fly larvae rarely use dead conspecifics as a food source. However, food deprivation largely enhances this behavior. We will now also investigate the underlying neural mechanisms that mediate this enhancement and compare it to the already described mechanism for a switch in olfactory choice behavior. Generally, this flexibility in foraging behavior enables the larva to explore a broader range of stimuli and to expand their feeding choices to overcome starvation.

An in-silico framework to study the cholinergic modulation of the neocortex

Neuromodulators control information processing in cortical microcircuits by regulating the cellular and synaptic physiology of neurons. Computational models and detailed simulations of neocortical microcircuitry offer a unifying framework to analyze the role of neuromodulators on network activity. In the present study, to get a deeper insight in the organization of the cortical neuropil for modeling purposes, we quantify the fiber length per cortical volume and the density of varicosities for catecholaminergic, serotonergic and cholinergic systems using immunocytochemical staining and stereological techniques. The data obtained are integrated into a biologically detailed digital reconstruction of the rodent neocortex (Markram et al, 2015) in order to model the influence of modulatory systems on the activity of the somatosensory cortex neocortical column. Simulations of ascending modulation of network activity in our model predict the effects of increasing levels of neuromodulators on diverse neuron types and synapses and reveal a spectrum of activity states. Low levels of neuromodulation drive microcircuit activity into slow oscillations and network synchrony, whereas high neuromodulator concentrations govern fast oscillations and network asynchrony. The models and simulations thus provide a unifying in silico framework to study the role of neuromodulators in reconfiguring network activity.

Psychological mechanisms and functions of 5-HT and SSRIs in potential therapeutic change: Lessons from the serotonergic modulation of action selection, learning, affect, and social cognition

Uncertainty regarding which psychological mechanisms are fundamental in mediating SSRI treatment outcomes and wide-ranging variability in their efficacy has raised more questions than it has solved. Since subjective mood states are an abstract scientific construct, only available through self-report in humans, and likely involving input from multiple top-down and bottom-up signals, it has been difficult to model at what level SSRIs interact with this process. Converging translational evidence indicates a role for serotonin in modulating context-dependent parameters of action selection, affect, and social cognition; and concurrently supporting learning mechanisms, which promote adaptability and behavioural flexibility. We examine the theoretical basis, ecological validity, and interaction of these constructs and how they may or may not exert a clinical benefit. Specifically, we bridge crucial gaps between disparate lines of research, particularly findings from animal models and human clinical trials, which often seem to present irreconcilable differences. In determining how SSRIs exert their effects, our approach examines the endogenous functions of 5-HT neurons, how 5-HT manipulations affect behaviour in different contexts, and how their therapeutic effects may be exerted in humans – which may illuminate issues of translational models, hierarchical mechanisms, idiographic variables, and social cognition.

Serotonergic activity in the dorsal raphe nucleus through the lens of unsupervised learning

COSYNE 2025

Neuroplastic effects of serotonergic psychedelics at the presynapse

Serotonergic Control of Model-based Decision Making

COSYNE 2022

Serotonergic Control of Model-based Decision Making

COSYNE 2022

Serotonergic neurons of the caudal raphe contribute to sensory processing during adaptive locomotion

FENS Forum 2024

Dissecting the Functional Organization of the Serotonergic System at Whole-Brain Scale in C. elegans

COSYNE 2023

Ethological foraging fingerprints reveal heterogeneous effects of serotonergic neuromodulation

COSYNE 2025

Serotonergic neurons in the dorsal raphe regulate visual attention

COSYNE 2025

Acute stress drives changes in co-transmitter identity in serotonergic neurons that promote sustained fear

Arginine vasopressin increases the excitatory synaptic drive and firing activity of developing serotonergic neurons in neonatal dorsal raphe nucleus

Beyond the reward prediction error: achieving reversal learning with Hebbian cortical plasticity and serotonergic modulation

Characterization of a habenula-driven serotonergic recurrent inhibitory network in dorsal raphe nucleus

Chronic maternal SSRI exposure during the prenatal and/or postnatal period induced vocal behavior deficits and affected serotonergic neurogenesis in the mouse offspring

Descending serotonergic facilitation contribution to DNIC analgesia in prolonged joint inflammatory pain

Developmental Disruption of Erbb4 in Pet1+ Neurons Impairs Serotonergic Sub-System Connectivity and Memory Formation

Early life chronic stress alters zebrafish dorsal raphe serotonergic neuron responses to subsequent stressor exposure

Effects of Neonatal Hypoxia on the Development of Serotonergic Innervation and Cognitive Functions

Impact and subcellular location of serotonergic modulation on retinal ganglion cell signalling

Melatonin Reduces Alcohol Drinking in Rats with Disrupted Function of the Serotonergic System

Modulation of the cortical state by serotonergic (5-HT) receptors: a study combining optogenetic tools and multi-channel electrode recordings in mouse visual cortex

Probing the neural circuit mediating the anxiolytic effects of a serotonergic psychedelic

Regulation of the endocannabinoid system by serotonergic psychedelics: a lipidomic and behavioral study in rodents

The role of serotonergic receptor 5-HTR4 in motor symptoms and L-DOPA-induced dyskinesia in Parkinson’s disease

Serotonergic and dopaminergic neurons in Dorsal Raphe Nucleus: from physiology to Parkinson’s Disease pathology

Serotonergic modulation of neural activity across the mouse brain

Single-axon dynamics of serotonergic neurons in ex vivo systems

Acute and chronic treatment with the nitric oxide synthase inhibitor agmatine stimulates serotonergic neurons in the rat dorsal raphe nucleus

FENS Forum 2024

Cadherin-13 deficiency impacts murine serotonergic circuitries and cognitive function

FENS Forum 2024

Cellular and molecular characterization of serotonergic synapses in a mouse model of depression and raphe synucleinopathy

FENS Forum 2024

Influence of serotonergic modulation in recovery after stroke

FENS Forum 2024

Mapping the projections of serotonergic dorsal raphe neurons in zebrafish

FENS Forum 2024

Neurochemical mechanisms underlying serotonergic modulation of neuroplasticity in humans

FENS Forum 2024

Role of the serotonergic dorsal raphe nucleus in mediating the effects of developmental chronic stress in zebrafish

FENS Forum 2024