Topic: dorsal raphe nucleus

The in vivo responses of dorsal raphe nucleus (DRN) serotonin neurons to emotionally-salient stimuli are a puzzle. Existing theories centred on reward, surprise, salience, and uncertainty individually account for some aspects of serotonergic activity but not others. Combining ideas from reinforcement learning (RL) theory with recent insights into the signal processing features of the DRN, here we find a unifying perspective in a prospective code for value. Such a code is both biologically realistic---it arises from strong spike-frequency adaptation in serotonin neurons coupled with slow decodi

Serotonin (5-HT) is implicated in decision-making, such as signaling prediction errors and cue values, as well as to the regulation of behavioral states of wakefulness and arousal, but the relationship between these two domains of function is not well understood. On one hand, serotonin activity is negatively associated with locomotor behavior, which has been seen as behavioral inhibition. On the other hand, serotonin transients are also associated with surprise or uncertainty, as well as novelty responses, including exploration-related facial movements (e.g., whisking, sniffing). Because ther

Neuromodulatory systems play a crucial role in the brain, driving rapid, global changes in neuronal computation and learning. While the dopaminergic system is thought to broadcast 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

It was previously reported that the nitric oxide synthase (NOS) inhibitor agmatine had anxiolytic and antidepressant-like effects in rodents (Aglawe et al Brain Res Bull 167:37, 2021). Since serotonergic (5-HT) neurons of the dorsal raphe nucleus (DRN), expressing NOS, had lower excitability than the non-NOS expressing ones (Gartside et al Eur J Neurosci 51:1881, 2020), the anxiolytic and antidepressant-like effects of agmatine might involve stimulation of 5-HT neurons of the DRN. The present study aimed to examine this hypothesis. Acute and chronic effects of agmatine were tested. In acute ex

Around 280 million people worldwide suffer from depression. However, treatment for this mood disorder is ineffective in 30% of patients. An important target for the treatment of depression is the dorsal raphe nucleus (DRN), which is the main source of serotonin (5-HT) to the forebrain. Previous research has shown that mecamylamine (Mec) increases the activity of 5-HT neurons by enhancing glutamate release through activation of α4β2 nicotinic receptors (nAChRs), while inhibiting GABAergic release by inhibiting α7 nAChRs in the DRN. This mechanism may explain its antidepressant properties. Howev

Parkinson’s disease (PD) is usually thought of as a motor disorder, although non-motor symptoms may precede the motor manifestations and are a key component of the PD. Among these, depression and anxiety are most prevalent symptoms and caused a greater symptomatic burden in women than in men. 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

We have reported that two types of ERs, ERa and ERb, are differentially involved in the estrogenic regulation of various kinds of social behaviors in both sexes of mice. In contrast to ERa-dependent action, the neuronal mechanisms of ERb action are still largely unknown. Using the ERb-RFPtg mouse line, we found a differential distribution of ERb from ERa at the “cellular level” in each of the ERb-rich brain regions in the social behavior neural network, such as the medial amygdala (MeA), lateral septum, and midbrain dorsal raphe nucleus (DRN). To further determine the functions of these ERb-ex

Current rehabilitation for stroke primarily relies on physiotherapy. 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 Dorsal Raphe Nucleus (DRN) is the largest of the serotonergic nuclei, but it also comprises a wide variety of neuronal subpopulations, including dopaminergic cells (DRNDA) and astrocytes, which may represent a source of local DRN modulation. The DRN participates in a wide range of behavioral responses related to the processing of aversive stimuli, leading to anxiety state. While the role of DRN5-HT and DRNDA in valence processing is emerging, the contribution of DRN astrocytes (DRNAstro), as well as the underpinning cellular mechanisms, remain elusive. Unpublished data from the lab indicat

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

The dorsal raphe nucleus (DRN) contains the largest population of serotonergic (5-HT) neurons in the central nervous system. The DRN modulates a wide range of physiological functions and brain states, mostly due to its widespread and heterogeneous projections. Evidence suggests that the DRN comprises different sub-systems with distinct neurotransmitter phenotype, connectivity and function. These sub-systems are difficult to characterize in the complex mammalian DRN. To overcome this, we address these questions in zebrafish larvae, leveraging their simpler and conserved DRN.Here, we establish a

Sharp wave ripples (SWR) represent synchronized activity of neuronal population in the mammalian hippocampus. They are thought to be associated with memory reactivation, transfer, and consolidation during sleep and awake immobility. In adults, it was shown that some subtypes of SWR are triggering precise activation across cortical areas accompanied by strong inhibition in subcortical areas (Logothetis et. al. 2012, Pedrosa et. al 2022) while other subtypes preferentially activates neuromodulatory structures such as the dorsal raphe nucleus and the locus coeruleus (Ramirez-Villega et. al 2015).

Neuronal circuits located in the midbrain play a critical role in controlling defensive behavior. However, it is still elusive how different neuron types contribute to distinct behavioral outcomes during the presence of threat. In this study, we investigated neurons expressing vasoactive intestinal polypeptide (VIP) in the ventral periaqueductal gray (PAG) and dorsal raphe nucleus in mice. These VIP-expressing neurons also expressed tyrosine hydroxylase (TH), a marker for dopaminergic cells. Using viral tracing conducted in Vip-Cre mice, we observed that these VIP-expressing neurons innervated

Cognitive flexibility is a function of the prefrontal cortex (PFC) that allows shifting strategies to adjust performance in changing environments. The dorsal raphe nucleus (DRN) provides most of the serotonergic inputs to the PFC. Clinical and pharmacological evidence suggests that prefrontal impairments or serotonergic alterations affect cognitive flexibility. However, the neuronal correlates of cognitive flexibility are largely unknown, and whether modulation of the neuronal activity in the DRN affects flexible behaviors remains unclear. We investigated how projections from the DRN modulate

The dorsal tegmentum including the ventrolateral PAG (vlPAG) and dorsal raphe nucleus (DRN) plays a critical role in controlling anxiety, fear memory formation, autonomic processes and most particularly, it is involved in descending modulation of pain processing. It has been shown that different neuron types, such as dopaminergic and serotonergic cells are part of this circuitry – besides the glutamatergic and GABAergic neurons – however their functions remained unclear. Here, we explored the neuronal activity in the vlPAG and DRN in urethane-anesthetized mice in response to different types of

The parabrachial nucleus (PBN) relays gustatory information as well as negative emotions. It sends dense projections to the ventral tegmental area (VTA), a heterogeneous brain region that regulates motivational behaviors. Nevertheless, the function of PBN-to-VTA connection remains elusive. To characterize the functional roles of PBN-to-VTA pathway, we first applied dual-viral retrograde tracing to specifically label VTA-projecting PBN cells. By combining c-Fos immunostainings with different behavior paradigms, we found that VTA-projecting PBN cells are significantly activated by negative affec

Chronic exposure to stressors is associated with the emergence of psychiatric disorders, but the underlying mechanisms are unclear. We previously showed that developmental chronic unpredictable stress (CUS) diminishes the habituation of dorsal raphe nucleus (DRN) serotonergic (5-HT) neurons to acute stressors and enhances anxiety-like responses. Here, we investigated whether the change in 5-HT DRN habitution underlies CUS-induced behavioural alterations. We exposed larval zebrafish to the CUS, subsequently ablated DRN 5-HT neurons using chemogenetics and assessed different types of anxiety-lik

The striatum is the predominant input structure of the striatum, receiving converging glutamatergic and GABAergic inputs from cortical and subcortical regions. It also receives modulatory input from midbrain dopamine neurons which has been shown to be critical for motor initiation, learning and reward. Additionally, the striatum also receives serotonergic input with one third of serotonergic neurons projecting from the dorsal raphe nucleus (DRN) to the striatum. Here, we studied the impact of 5-HT on the interactions between Cholinergic interneurons (ChINs). ChINs are key modulators of striata

The degeneration of dopamine neurons of the substantia nigra pars compacta is well-known in motor symptoms of Parkinson’s disease (PD). However, other dopaminergic populations degenerate and give rise to non-motor symptoms such as anxiety which has a high prevalence in PD patients and strongly affects quality of life. One of these structures, the dorsal raphe nucleus (DRN), has been identified as a potential structure involved in anxiety and depression in PD. Indeed, the dopaminergic neurons of the DRN degenerate in PD, and a part of them co-releases the vaso-intestinal peptide (VIP) onto two

The dorsal raphe nucleus (DRN) modulates diverse behaviors and brain functions through its extensive serotonergic projections across the forebrain. Recent studies showed that vertebrate DRN is composed of distinct types of molecularly defined and topographically organized populations of neurons that are evolutionarily conserved. However, how and what do these topographically organized DRN neuron ensembles communicate to the forebrain, and the role of DRN in forebrain computations and animal behavior remain elusive. Here, we employed two-photon calcium imaging in juvenile zebrafish to investiga