Serotonin Neuron Diversity in the Dorsal Raphe

Andrade, Rodrigo; Haj‐Dahmane, Samir

doi:10.1021/cn300224n

Cited by 50 publications

(27 citation statements)

References 36 publications

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“…Different populations of 5-HTergic neurons in the dorsal raphe (DR) nucleus exist that differentially contribute to the response to stress. As mentioned before differentiation of subpopulations of 5-HT neurons could also be a factor contributing to the development of anxiety disorders (Gaspar and Lillesaar, 2012; Andrade and Haj-Dahmane, 2013). Although Jasinska et al (2012) hypothesize this mechanism mainly for depression, there is no a priory reason why anxiety disorders would not be mediated by this or a similar mechanism.…”

Section: Translational Studies Into Anxietymentioning

confidence: 85%

“…Moreover, Pet1 knock-out mice showed reduced anxiety-like behavior in conflict-tests, but increased fear in aversive conditioning paradigms. Thus, Pet1 plays an important role in the acquisition and maintenance of 5-HT identity (Gaspar and Lillesaar, 2012; Andrade and Haj-Dahmane, 2013). These findings suggest that the differentiation of subpopulations of 5-HT neurons could also be a factor contributing to the development of anxiety disorders.…”

Section: Preclinical Genetic Approaches To Anxietymentioning

confidence: 99%

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The role of the serotonergic and GABA system in translational approaches in drug discovery for anxiety disorders

2013

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There is ample evidence that genetic factors play an important role in anxiety disorders. In support, human genome-wide association studies have implicated several novel candidate genes. However, illumination of such genetic factors involved in anxiety disorders has not resulted in novel drugs over the past decades. A complicating factor is the heterogeneous classification of anxiety disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) and diverging operationalization of anxiety used in preclinical and clinical studies. Currently, there is an increasing focus on the gene × environment (G × E) interaction in anxiety as genes do not operate in isolation and environmental factors have been found to significantly contribute to the development of anxiety disorders in at-risk individuals. Nevertheless, extensive research on G × E mechanisms in anxiety has not resulted in major breakthroughs in drug discovery. Modification of individual genes in rodent models has enabled the specific study of anxiety in preclinical studies. In this context, two extensively studied neurotransmitters involved in anxiety are the gamma-aminobutyric acid (GABA) and 5-HT (5-hydroxytryptamine) system. In this review, we illustrate the complex interplay between genes and environment in anxiety processes by reviewing preclinical and clinical studies on the serotonin transporter (5-HTT), 5-HT1A receptor, 5-HT2 receptor, and GABAA receptor. Even though targets from the serotonin and GABA system have yielded drugs with known anxiolytic efficacy, the relation between the genetic background of these targets and anxiety symptoms and development of anxiety disorders is largely unknown. The aim of this review is to show the vast complexity of genetic and environmental factors in anxiety disorders. In light of the difficulty with which common genetic variants are identified in anxiety disorders, animal models with translational validity may aid in elucidating the neurobiological background of these genes and their possible role in anxiety. We argue that, in addition to human genetic studies, translational models are essential to map anxiety-related genes and to enhance our understanding of anxiety disorders in order to develop potentially novel treatment strategies.

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Section: Translational Studies Into Anxietymentioning

confidence: 85%

Section: Preclinical Genetic Approaches To Anxietymentioning

confidence: 99%

The role of the serotonergic and GABA system in translational approaches in drug discovery for anxiety disorders

2013

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“…Lastly, we identified neuron populations extrinsic to the olfactory system which provide strong input to the CSDn at locations within the protocerebrum and in select food-associated AL glomeruli, respectively. Population-level diversity and heterogeneity allow modulatory neurons to influence a diverse range of behaviors, often in a context-dependent manner [3-5, 8-16, 87, 88]. Our study illustrates the extent to which a single serotonergic neuron can have distinct connectivity within and across olfactory brain regions.…”

Section: Discussionmentioning

confidence: 92%

“…In mammals, one ubiquitous neuromodulator, serotonin, is released by tens of thousands to hundreds of thousands of neurons which originate in the raphe nuclei and project throughout the brain [6, 7]. Serotonergic raphe neurons are highly diverse in their projections, connectivity, and electrophysiological properties, and are implicated in a wide breadth of behaviors and physiological processes [4, 8–16]. Further, the raphe system receives monosynaptic input from up to 80 anatomical areas [8, 9].…”

Section: Introductionmentioning

confidence: 99%

The wiring logic of an identified serotonergic neuron that spans sensory networks

Coates

Calle-Schuler

Helmick

et al. 2020

Preprint

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19Serotonergic neurons modulate diverse physiological and behavioral processes in a 20 context-dependent manner, based on their complex connectivity. However, their 21 connectivity has not been comprehensively explored at a single-cell resolution. Using a 22 whole-brain EM dataset we determined the wiring logic of a broadly projecting 23 serotonergic neuron (the "CSDn") in Drosophila. Within the antennal lobe (AL; first-order 24 olfactory region), the CSDn receives glomerulus-specific input and preferentially targets 25 distinct local interneuron subtypes. Furthermore, the wiring logic of the CSDn differs 26 between olfactory regions. The CSDn innervates the AL and lateral horn (LH), yet does 27 not maintain the same synaptic relationship with individual projection neurons that also 28 span both regions. Consistent with this, the CSDn has more distributed connectivity in 29 the LH relative to the AL, preferentially synapsing with principal neuron types based on 30 presumptive transmitter content. Lastly, we identify protocerebral neurons that provide 31 abundant synaptic input to the CSDn. Our study demonstrates how an individual 32 modulatory neuron can interact with local networks and integrate input from non-33 olfactory sources. 35Introduction 36 Every neural network receives modulatory input from a variety of sources [1, 2], 37 and in some cases from heterogeneous populations of neurons that release the same 38 modulatory transmitter [3][4][5]. In mammals, one ubiquitous neuromodulator, serotonin, is 39 released by tens of thousands to hundreds of thousands of neurons which originate in 40 the raphe nuclei and project throughout the brain [6, 7]. Serotonergic raphe neurons are 41 highly diverse in their projections, connectivity, and electrophysiological properties, and 42 2 are implicated in a wide breadth of behaviors and physiological processes [4,[8][9][10][11][12][13][14][15][16]. 43 Further, the raphe system receives monosynaptic input from up to 80 anatomical areas 44 [8, 9]. As a result, a significant amount of work has focused on disentangling the 45 functional and behavioral roles of serotonergic neurons. Several recent studies have 46 suggested that serotonergic raphe neurons may be organized into functional 47 subpopulations based on neuroanatomy, electrophysiology, and behavior [4, 12,[17][18][19][20][21]. 48For example, two parallel sub-systems of serotonergic raphe neurons collateralize 49 complimentarily and are both activated by reward, yet have opposing responses to 50 aversive stimuli and promote distinct behaviors [18]. Sparse neuron reconstructions in 51 mice show that a single serotonin neuron can interconnect the olfactory bulb, piriform 52 cortex, and anterior olfactory nucleus [19], demonstrating that a single serotonergic 53 neuron can arborize several processing stages within the same sensory modality. Thus, 54 determining the precise patterns of connectivity of single serotonergic neurons within 55 and across the brain regions will be critical for understanding t...

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“…AgNOR-параметры определяли раздельно в каждом из подъядер DRN: вентральном, вентролатеральном, дорсальном, межфасцикулярном [8]. В одном гистологическом препарате исследовали в среднем 20 наиболее крупных нейронов (магноциты) с хорошо различимыми границами ядер и областей AgNOR.…”

Section: материал и методыunclassified

The characteristic of protein biosynthesis in brain neurons with chronic alcohol intoxication

Morozov

Velenko

2018

Sud.-med. ekspert.

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The objective of the present study was to evaluate the possibilities for the use of the changes in the AgNOR staining patterns in the neurons of the dorsal raphe nucleus (DRN) for the purposes of the medical differential diagnostics of the cases of death from chronic alcohol intoxication. We elucidated the characteristics of the activity of protein biosynthesis including the number and the area of the nucleoli in the nuclei of the neurons of the individuals who had died from chronic alcohol intoxication (n=20) in comparison with the subjects of the control group (n=13). To reveal the morphological structures associated with protein biosynthesis in the nucleoli of the serotoninergic neurons of the dorsal raphe nucleus in the brain, the histological preparations were stained with the use of the silver-staining technique for nucleolar organizer regions (AgNOR). The comparative statistical analysis of the results thus obtained with the calculated confidence coefficients was carried out. The aggregated analysis of all the dorsal raphe subnuclei revealed the impairment of the AgNOR staining characteristics in the neurons of the subjects who had died from chronic alcohol intoxication in comparison with those of the subjects comprising the control group. It is concluded that the results of the study can be used for differential diagnostics of deaths from chronic alcohol intoxication and other causes.

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Serotonin Neuron Diversity in the Dorsal Raphe

Cited by 50 publications

References 36 publications

The role of the serotonergic and GABA system in translational approaches in drug discovery for anxiety disorders

The role of the serotonergic and GABA system in translational approaches in drug discovery for anxiety disorders

The wiring logic of an identified serotonergic neuron that spans sensory networks

The characteristic of protein biosynthesis in brain neurons with chronic alcohol intoxication

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