Introducing the brain: astrocyte actions (Introduction)

by David Turell , Monday, December 12, 2022, 18:40 (494 days ago) @ David Turell

In control of synapses:

https://medicalxpress.com/news/2022-12-highlights-role-astrocytes-synaptic-vta.html

"Researchers at the CNR Institute of Neuroscience and the University of Padua, the Italian Institute of Technology (IIT) and the Polytechnic University of Le Marche in Italy have recently carried out a study investigating the so far elusive role of astrocytes in the so-called ventral tegmental area (VTA), a hub of the mesocorticolimbic circuitry that plays fundamental roles in cognition, locomotion, reward, motivation and aversion. Their findings, published in Nature Neuroscience, suggest that astrocytes participate to the synaptic regulation of VTA dopamine neurons.

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"The key idea behind the research by Carmignoto and his colleagues is that the functioning of the brain relies on a network of highly interacting neurons and astrocytes. In their recent study, they set out to specifically examine the role of astrocytes in the VTA circuitry, which was rarely explored in previous literature.

"Past findings suggest that the release of dopamine and endocannabinoids at the level of dopaminergic neuronal dendrites can act on both presynaptic terminals and postsynaptic neurons to modulate activity in the VTA. Carmignoto and his colleagues set out to explore the possibility that these previously reported neuronal signals also recruit astrocytes, which in turn modulate VTA synaptic circuitry.

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"'In light of the results we obtain, we propose that astrocytes are activated by dopamine and endocannabinoids. Indeed, in collaboration with Fiorenzo Conti's group, we provide evidence that burst-firing neurons induce recurring calcium elevations in nearby astrocytes through activation of both dopamine type-2 and endocannabinoid type-1 receptors."

"Carmignoto and his colleagues then conducted a series of experiments using an electron microscope, which confirmed that dopamine type-2 and endocannabinoid type-1 receptors were co-expressed in astrocytes. Using pharmacological and genetic techniques, they also demonstrated that the activation of these two receptors in astrocytes, probably followed by the release of glutamate, play a key role in regulating synaptic transmission onto VTA dopaminergic neurons.

"Finally, the researchers used chemogenetic tools to selectively activate astrocytes in the VTA of living mice and observe resulting activity in the region. Their observation revealed that astrocytes regulate the burst firing of VTA dopamine neurons and induce hyperlocomotion.

"'We identified a hitherto unknown, sex and age-dependent, astrocyte-mediated mechanism of long-term synaptic potentiation of the excitatory transmission onto VTA dopaminergic neurons," Carmignoto said. "Consistent with the key role that the excitatory transmission exerts on the firing activity of VTA dopaminergic neurons, in collaboration with Annalisa Muntoni in Cagliari and Francesco Papaleo in Genova, we found that in vivo astrocyte activation increases the burst firing of dopamine neurons in the VTA and induces locomotor hyperactivity, a behavior that is known to be associated with increased activity of VTA dopaminergic neurons.

"'This is, in our opinion, an important observation, as the burst firing of VTA dopamine neurons is the code used by dopamine neurons to regulate dopamine release at multiple VTA target regions, thereby controlling various behavioral states including reward and aversion, learning, motivation, attention and locomotor activity."

"Overall, the recent work by this team of researchers advances the hypothesis that the reciprocal communication between astrocytes and neurons in the VTA plays a crucial role in the manifestation of dopamine-dependent behaviors. These behaviors are known to be associated with numerous psychiatric conditions, including obsessive-compulsive disorder and drug addiction."

Comment: more complexity found in the control systems in the brain with astrocytes shown to be so active.