Do stars govern our actions? Astrocyte involvement in rodent behavior

Oliveira, João Filipe; Sardinha, Vanessa Morais; Guerra‐Gomes, Sónia; Araque, Alfonso; Sousa, Nuno

doi:10.1016/j.tins.2015.07.006

Cited by 153 publications

(127 citation statements)

References 115 publications

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“…Through glutamate uptake, astrocytes are also involved in higher brain functions, such as learning and memory114546. We demonstrate here that EAAT2 operates over a highly controlled range to allow the emergence of bidirectional STDP.…”

Section: Discussionmentioning

confidence: 76%

“…Astrocytes actively control various synaptic functions and, therefore, play a key role in the modulation of neuronal activity11124546. Control of neuronal computation by astrocytes is via the release and uptake of transmitters, such as glutamate.…”

Section: Discussionmentioning

confidence: 99%

“…A few studies have reported effects of changes in EAAT2 expression on behaviour46. The pharmacological blockade of EAAT2 with DHK impairs spatial memory and induces depression and anhedonia and ceftriaxone has been reported to display antidepressant effects46.…”

Section: Discussionmentioning

confidence: 99%

“…The pharmacological blockade of EAAT2 with DHK impairs spatial memory and induces depression and anhedonia and ceftriaxone has been reported to display antidepressant effects46. EAAT2 downregulation in striatum is also found in a rat model of depression59.…”

Section: Discussionmentioning

confidence: 99%

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Astrocytes gate Hebbian synaptic plasticity in the striatum

Valtcheva

Venance

2016

Nat Commun

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Astrocytes, via excitatory amino-acid transporter type-2 (EAAT2), are the major sink for released glutamate and contribute to set the strength and timing of synaptic inputs. The conditions required for the emergence of Hebbian plasticity from distributed neural activity remain elusive. Here, we investigate the role of EAAT2 in the expression of a major physiologically relevant form of Hebbian learning, spike timing-dependent plasticity (STDP). We find that a transient blockade of EAAT2 disrupts the temporal contingency required for Hebbian synaptic plasticity. Indeed, STDP is replaced by aberrant non-timing-dependent plasticity occurring for uncorrelated events. Conversely, EAAT2 overexpression impairs the detection of correlated activity and precludes STDP expression. Our findings demonstrate that EAAT2 sets the appropriate glutamate dynamics for the optimal temporal contingency between pre- and postsynaptic activity required for STDP emergence, and highlight the role of astrocytes as gatekeepers for Hebbian synaptic plasticity.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Astrocytes gate Hebbian synaptic plasticity in the striatum

Valtcheva

Venance

2016

Nat Commun

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“…Astrocytes provide crucial metabolic and structural support (3,4) and are key players in neurotransmission (5-7) and behavior (8). The status of many major redox couples in the brain is also regulated by astrocytes (9), through their high content of antioxidant compounds and enzymes (10) and by the constitutive stabilization of the master antioxidant transcriptional activator, nuclear factor erythroid 2-related factor 2 (Nrf2) (11).…”

mentioning

confidence: 99%

Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes

López-Fabuel

Douce

Logan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

307

245

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Neurons depend on oxidative phosphorylation for energy generation, whereas astrocytes do not, a distinctive feature that is essential for neurotransmission and neuronal survival. However, any link between these metabolic differences and the structural organization of the mitochondrial respiratory chain is unknown. Here, we investigated this issue and found that, in neurons, mitochondrial complex I is predominantly assembled into supercomplexes, whereas in astrocytes the abundance of free complex I is higher. The presence of free complex I in astrocytes correlates with the severalfold higher reactive oxygen species (ROS) production by astrocytes compared with neurons. Using a complexomics approach, we found that the complex I subunit NDUFS1 was more abundant in neurons than in astrocytes. Interestingly, NDUFS1 knockdown in neurons decreased the association of complex I into supercomplexes, leading to impaired oxygen consumption and increased mitochondrial ROS. Conversely, overexpression of NDUFS1 in astrocytes promoted complex I incorporation into supercomplexes, decreasing ROS. Thus, complex I assembly into supercomplexes regulates ROS production and may contribute to the bioenergetic differences between neurons and astrocytes.redox | brain | bioenergetics | lactate | glycolysis T he brain is a metabolically demanding organ (1) that requires tight cooperation between neurons and astrocytes (2). Astrocytes provide crucial metabolic and structural support (3, 4) and are key players in neurotransmission (5-7) and behavior (8). The status of many major redox couples in the brain is also regulated by astrocytes (9), through their high content of antioxidant compounds and enzymes (10) and by the constitutive stabilization of the master antioxidant transcriptional activator, nuclear factor erythroid 2-related factor 2 (Nrf2) (11). Thus, astrocytes are equipped to protect themselves when exposed to excess reactive oxygen species (ROS) (12) and reactive nitrogen species (13,14). Moreover, astrocytes also provide nearby neurons with protective antioxidant precursors through a cell-signaling mechanism involving glutamate receptor activation by neurotransmission (11,15,16). The tight coupling between astrocytes and neurons therefore helps in energy and redox metabolism during normal brain function.Intriguingly, the ATP used by neurons is supplied by oxidative phosphorylation, whereas most energy needs of astrocytes are met by glycolysis (17). In fact, the survival of neurons requires oxidative phosphorylation (18,19). The different energy metabolisms of the two cell types are closely coupled, with astrocytes releasing the glycolytic end product, lactate, which is used by neighboring neurons to drive oxidative phosphorylation (20)(21)(22). As the molecular mechanisms underlying the markedly different modes of ATP production in the two cell types are not understood, we investigated whether the organization of the mitochondrial respiratory chain in brain cells could contribute. Here, we report that the extent of supercomplex f...

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Morphometric analysis of astrocytes in vocal production circuits of common marmoset (Callithrix jacchus)

Turk

SheikhBahaei

2021

J of Comparative Neurology

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Astrocytes, the star-shaped glial cells, are the most abundant non-neuronal cell population in the central nervous system. They play a key role in modulating activities of neural networks, including those involved in complex motor behaviors. Common marmosets (Callithrix jacchus), the most vocal non-human primate (NHP), have been usedto study the physiology of vocalization and social vocal production. However, the neural circuitry involved in vocal production is not fully understood. In addition, even less is known about the involvement of astrocytes in this circuit. To understand the role, that astrocytes may play in the complex behavior of vocalization, the initial step may be to study their structural properties in the cortical and subcortical regions that are known to be involved in vocalization. Here, in the common marmoset, we identify all astrocytic subtypes seen in other primate's brains, including intralaminar astrocytes. In addition, we reveal detailed structural characteristics of astrocytes and perform morphometric analysis of astrocytes residing in the cortex and midbrain regions that are associated with vocal production. We found that cortical astrocytes in these regions illustrate a higher level of complexity when compared to those in the midbrain. We hypothesize that this complexity that is expressed in cortical astrocytes may reflect their functions to meet the metabolic/structural needs of these regions.

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Do stars govern our actions? Astrocyte involvement in rodent behavior

Cited by 153 publications

References 115 publications

Astrocytes gate Hebbian synaptic plasticity in the striatum

Astrocytes gate Hebbian synaptic plasticity in the striatum

Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes

Morphometric analysis of astrocytes in vocal production circuits of common marmoset (Callithrix jacchus)

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