Project description
Understanding cognitive flexibility deficiencies
The cognitive flexibility required for behavioural adaptation to environmental changes is attributed primarily to the prefrontal cortex (PFC). However, the exact mechanisms underlying these processes remain largely unknown. Inhibitory GABAergic interneurons seem to have a central role in this process. Interestingly, different interneurons subsets exhibit different anatomical and physiological characteristics suggesting distinct functionality. The EU-funded GinieEffect will combine genetic, imaging and behavioural techniques in freely moving mice with in silico studies to dissect the effects of long-term dysregulation of different interneurons subsets on the PFC circuit function. The results will advance our understanding of cognitive flexibility mechanisms and will allow the development of new therapeutic strategies for several disorders with cognitive flexibility defects.
Objective
Covid-19 pandemic has highlighted the importance of making decisions and adjusting our behavioural strategy to tackle unexpected changes in our environment. The cognitive flexibility required to modify behaviour when the rules change is ascribed primarily to the prefrontal cortex (PFC), but the exact mechanisms underlying this phenomenon remain unknown. Inhibitory GABAergic interneurons (INs) seem to play a key role in this process by modulating the primary excitatory pyramidal neurons’ activity in the PFC. Indeed, individuals who have deficits in these INs, a common feature in many mental disorders, often fail to adjust their behaviour to a rule change, even though their ability to learn an initial rule remains intact. The two, main IN subsets, Parvalbumin-positive (PV) and Somatostatin-positive (SST) have different anatomical and physiological characteristics suggesting distinct functions. We, thus, hypothesize distinct roles for each subtype: PV cells may control the gain in pyramidal neuron activity, thereby affecting behaviour. SST cells, however, may control the ability to learn a new rule via plasticity in dendrites, thereby affecting behaviour, but leaving pyramidal neurons activity intact. Combining genetic, imaging and behavioural techniques in freely moving mice with in silico studies, we will dissect the effects of of long-term dysregulation of PV and SST INs on the PFC circuit function, with respect to flexible behaviour. Our experimental results will be fed to a computational model of the PFC circuit to further investigate how interneuronal control of information affects cognitive flexibility and to explore mechanisms that can reverse cognitive flexibility defects. Unravelling the mechanistic role of cognitive flexibility in the PFC will not only further our understanding of a complex brain function. It will also open new avenues for developing therapeutic approaches for numerous mental disorders, thus ameliorating a large societal and economic burden.
Fields of science
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
70013 Irakleio
Greece