Introducing the brain:astrocyte epigenetic control of neuron (Introduction)

by David Turell , Friday, June 16, 2023, 18:30 (315 days ago) @ David Turell

Helps explain brain adaption to new stimuli:

https://www.sciencemagazinedigital.org/sciencemagazine/library/item/16_june_2023/410885...

"Sardar et al. report a newly identified role for the monoamine neurotransmitter serotonin in inducing epigenetic histone modifications in astrocytes that alter inhibitory neurotransmitter signaling and ultimately sculpt olfactory processing and behavior in mice.

"Astrocytes are an integral part of brain circuits: They undergo intracellular calcium fluctuations in response to physiological sensory-driven neuronal activity that elicit the calcium-dependent release of neuroactive molecules that affect neural activity, plasticity, and behavior. It is becoming evident that the influence of astrocytes on neurons is multifold and is specific to developmental stages, brain regions, activity regimes, and pathophysiological states. Hence, the regulation of neuronal activity by astrocytes is remarkably specific yet flexible.

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"Sardar et al. identify a mechanism through which neuronal activity induces transcriptomic changes in astrocytes, which in turn drive epigenetic changes and regulate olfactory sensory processing in mice. They show that neuronal activity, artificially evoked using chemogenetics or physiologically triggered through olfactory stimulation, induces widespread changes in gene expression in astrocytes in a brain region–dependent manner. The expression of immediate early genes—a set of genes that are rapidly and transiently expressed in response to various stimuli—were specific to astrocytes and included transcription factors such as SOX9. The evoked neuronal activity increases binding of SOX9 to the promoter of the solute carrier family 22 member 3 (Slc22a3) gene. This gene encodes the monoamine transporter organic cation transporter 3 (OCT3), which contributes to the uptake of serotonin. SOX9-mediated upregulation of Slc22a3 expression was specific to the olfactory bulb; deleting Sox9 did not affect Slc22a3 expression in the cortex or hippocampus. This up-regulation in OCT3 expression increases levels of astroglial serotonin, which enters the nucleus to drive histone serotonylation.

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"What is the role of such histone modification? Using conditional deletion of Slc22a3, Sardar et al. show that Slc22a3 up-regulation induced by histone serotonylation increases the expression of monoamine oxidase B (MAOB), a biosynthetic enzyme of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Increased MAOB expression was associated with enhanced levels of GABA and its release by astrocytes, leading to increases in inhibitory synaptic transmission. Behaviorally, the GABA-mediated olfactory sensory processing allows responses to scents and ultimately contributes to odor detection and discrimination in mice. This translated to an enhancement of the ability of mice to detect new scents present at low concentration and to distinguish between structurally similar odorants.

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"What may be the advantage of such activity-dependent epigenetic regulation in several cell types? Considering that an astrocyte contacts hundreds of thousands of synapses, downstream effects of histone serotonylation could be broadcast to a large neuronal population. This is particularly suitable for the circuit-wide plasticity that is needed to discriminate scents.
Could other neuromodulators, such as catecholamines and histamine, also modulate changes that adaptively affect synaptic and circuit functions? Both the potential diversity in histone monoaminylation and regional specificities highlighted in the study of Sardar et al. could support the tailored regulation of gene expression according to local activity-dependent needs."

Comment: the knowledge of astrocyte activity is growing rapidly and contributes to our realizing just how complex is our brains underlying design. Not by chance.