Decoding the neuron-astrocyte dialogue that supports cognitive processing

Cognitive functioning is the intellectual activity that includes mental processes, such as, attention, learning and memory, executive function, verbal fluency, and working memory. In the neuroscience field, thousands of studies linked these computational processes to specific brain regions, and within these, to defined cellular circuits that operate in excitatory-inhibitory balances. These balances are required for normal cognitive processing, while its malfunction often leads to cognitive deficits. Brain circuits are composed of neuron ensembles and glial cells. In the last thirty years, the classical paradigm that brain computation is based exclusively on neuronal processing has been challenged by the emerging body of evidence describing dynamic neuron-glia interactions within brain circuits. Astrocytes – a type of glia that is found in large numbers throughout the mammalian brain – are highly active and dynamic cells, influencing a myriad of processes from homeostatic control to synaptic modulation. The neuron-astrocyte dialogue is nowadays widely accepted, and it has been demonstrated in several brain regions, namely those responsible for cognitive computation such as the hippocampus and the cortex. As expected, recent studies from us and others showed that these interactions at the cellular level are critical for the computation of complex cognitive behaviors.
The main objective of this project is to dissect the cellular mechanisms by which astrocytes influence cognitive functions processed by the prefrontal cortex. This main goal will be addressed by using different strategies to rescue cognitive function impaired in models of astrocytic dysfunction.

Funding Agency

FCT; Bial Foundation

Project Reference

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Project Members

João Oliveira

Principal Investigator Project Leader

Daniela Abreu

PhD Student

João F Viana

PhD Student

João Machado

PhD Student

Main Project Outcomes

Publications:
– Oliveira J, Araque A. 2022 Astrocyte regulation of neural circuit activity and network states. Glia. In press
Escartin C, Galea E, … Oliveira JF, … Sofroniew MV, Verkhratsky A. (2021) Reactive astrocyte nomenclature, definitions, and future directions. Nature Neuroscience 1–14.
Batiuk MY, Martirosyan A, Wahis J, Vin F de, Marneffe C, Kusserow C, Koeppen J, Viana JF, Oliveira JF, Voet T, Ponting CP, Belgard TG, Holt MG. (2020) Identification of region-specific astrocyte subtypes at single cell resolution. Nature Communications 11:1–15. IF=11.9;
Guerra-Gomes S, Sousa N, Pinto L, Oliveira JF (2018) Functional roles of astrocyte calcium elevations: from synapses to behavior. Front Cell Neurosci 11:427.
Sardinha VM, Guerra-Gomes S, Caetano I, Tavares G, Martins M, Reis JS, Correia JS, Teixeira-Castro A, Pinto L, Sousa N, Oliveira JF (2017) Astrocytic signaling supports hippocampal–prefrontal theta synchronization and cognitive function. Glia 65:1944–1960.
Tavares G, Martins M, Correia JS, Sardinha VM, Guerra-Gomes S, Neves SP das, Marques F, Sousa N, Oliveira JF. (2016). Employing an open-source tool to assess astrocyte tridimensional structure. Brain Structure Function 1–11.
Oliveira JF, Sardinha VM, Guerra-Gomes S, Araque A, Sousa N (2015). Do stars govern our actions? Astrocyte involvement in rodents’ behavior. Trends in Neurosciences 38:535–549.
Lima A, Sardinha VM, Oliveira AF, Reis M, Mota C, Silva MA, Marques F, Cerqueira JJ, Pinto L, Sousa N, Oliveira JF (2014) Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats. Molecular Psychiatry 19, 834–841.

Awards/grants:
2019: Travel Grant Marie Curie Alumni Association
2019: IBRO/PERC Grant – ICVS Satellite Meeting
2012: Marie Curie Intereuropean Fellowship

Projects: 8 as PI (4 ongoing) – 1.2+ million euro

Patent: PPP117831 (provisional)