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Discovery of new pathways controlling the serotonergic system.

With the aid of new methods, a research team at Karolinska Institutet have developed a detailed map of the networks of the brain that control the neurotransmitter serotonin. The study, published in the scientific journal Neuron, may lead to new knowledge on a number of psychiatric conditions and the development of new pharmaceuticals.

The neurotransmitter serotonin controls impulsivity, mood and our cognitive functions, among other things, and comes from the serotonergic neurons, the neurons that produce serotonin. So that humans have good mental health and normal behaviour, it is important that there is correctly regulated activity among these neurons. The activity is governed by other neurons from different regions of the brain via direct links, known as synapses, on the serotonergic neurons. Imbalance in the serotonergic system can lead to depression, Parkinson’s disease, schizophrenia and autism, among other things.

So far it has been impossible to study in detail how different types of nerve cells are interlinked and how the brain’s networks control behaviour. Consequently, there has also been a lack of knowledge of which nerve cells control the activity of the serotonergic neurons. But with the help of new methods, researchers at Karolinska Institutet can now investigate how the various networks of the brain are organised and how they work. The team has established which networks of the brain control the serotonergic neurons.

The researchers have created a new type of map of the neurons’ contacts and discovered new pathways that control the serotonergic system. These networks were previously unknown and are very interesting in terms of how they help he medical community to understand how the serotonergic system works, which could also help researchers to understand certain mental illnesses.

In order to map out which neurons have direct contact with serotonergic neurons, the researchers established a method in which these cells were marked with a rabies virus which produced a fluorescent marker. Via genetic manipulation, the rabies virus was then spread to all of the neurons directly linked to the serotonergic neurons. The researchers thereby gained a very detailed, three-dimensional image of the networks of the brain that control serotonin. Using optogenetics, a method in which light is used to control the activity of neurons, the researchers were then able to manipulate select networks and thus study their effect on the serotonergic neurons.

Via mapping, the researchers discovered a network in the frontal lobe which is associated with cognition and well-being and which controls the serotonergic neurons. Researchers also found that serotonin can be controlled from new types of neurons in the basal ganglia, an area of the cerebrum which among other things controls movement, well-being and decision-making; a discovery which may have significance for conditions such as Parkinson’s disease.

The team are very optimistic that the revolution they are now seeing in brain research could also lead to entirely new and effective medicine in the field of psychiatry.

Source:  Karolinska Institutet

 

Whole-Brain Model and Hyperdirect Circuitry of Monosynaptic Inputs onto Serotonergic Neurons.  (A) A whole-brain model of selected prominent monosynaptic inputs onto serotonergic neurons.  Inputs shown onto serotonergic neurons (5-HT) from isocortex (ACA, AI, RSP), striatum (STRd, STRv), caudal pallidum (PALc), thalamus (LH, MTN), central amygdala nucleus (CEA), and hypothalamus (LHA, ZI). Line thickness represents input numbers.  (B) An updated circuitry model based on the cell-type-specific inputs to serotonergic neurons (5-HT). Conventional model adapted from Nakamura (2013). Excitatory inputs depicted with circles, inhibitory inputs with rectangles.  Colour scheme is based on the Allen reference mouse brain atlas.  Meletis et al 2014.
Whole-Brain Model and Hyperdirect Circuitry of Monosynaptic Inputs onto Serotonergic Neurons. (A) A whole-brain model of selected prominent
monosynaptic inputs onto serotonergic neurons. Inputs shown onto serotonergic neurons (5-HT) from isocortex (ACA, AI, RSP), striatum (STRd, STRv), caudal pallidum (PALc), thalamus (LH, MTN), central amygdala nucleus (CEA), and hypothalamus (LHA, ZI). Line thickness represents input numbers. (B) An updated circuitry model based on the cell-type-specific inputs to serotonergic neurons (5-HT). Conventional model adapted from Nakamura (2013). Excitatory inputs depicted with circles, inhibitory inputs with rectangles. Colour scheme is based on the Allen reference mouse brain atlas. Meletis et al 2014.

 

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2 thoughts on “Discovery of new pathways controlling the serotonergic system. Leave a comment

  1. Role of Serotonin and Dopamine System Interactions in the Neurobiology of Impulsive Aggression and its Co-occurrence with other Clinical Disorders

    I am posting a comment which is a similar topic and one fairly interesting analogous to the piece you blogged about that grabbed my eye.Upon some research in peer-reviewed journals, namely in the National Institutes of Health, the paper I have titled above (and cited below) proposes a modified diathesis-stress model of impulsive aggression in which the underlying biological datasets may be deficient serotonergic function in the ventral prefrontal cortex of the brain.

    This underlying disposition can be manifested behaviorally, as impulsive aggression towards oneself and others, and as depression under precipitating life stressors. Substance abuse associated with impulsive aggression is understood in the context of dopamine dysregulation resulting from serotonergic deficiency.

    What I find exciting about the “end result” (my speak” as the eternal optimist for our future as humans, solving (also~dare I say; the future’s research directions in the areas of disease and disorder)…well, are (in my opinion) positive.

    I think I got fairly long winded in my excitement, so anyway, the neurobiology of impulsive aggression and its disorders in the future will focus on the interaction between serotonin and dopamine, because of their well-established relations with impulsive aggression and their significance in explaining these disorders, or co-occurring disorders along with other clinical disorders.
    .
    Dongju Seo, Christopher J. Patrick, Patrick J. Kennealy
    Aggress Violent Behav. Author manuscript; available in PMC 2009 October 1.

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