Circdyn · Optical Interrogation of Hippocampal Dentate Granule Circuit Dynamics in Health and Disease
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-01-01 → 2018-12-31
- EU contribution
- €175,420
- Participants
- 1
- Scheme
- MSCA-IF
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Results in brief
Optical Interrogation of Hippocampal Dentate Granule Circuit Dynamics in Health and Disease
The specific objectives of my H2020 MSCA proposal was to establish a decision-making task amenable to all-optical recording, and apply large-scale, chronic calcium imaging in awake behaving mice to measure neural activity to determine their causal role in such behavior and to test for a potential contribution of neural circuit alterations in animal models of neurodevelopmental disorders such as Rett syndrome (RTT). This work is extended to study decision-making in behavioural flexibility that we are about to submit as a manuscript. The work on behavioural flexibility is now extended to RTT animals that show deficiency of cognitive flexibility. Understanding neural correlates of brain dynamics in health and brain disorders is a fundamental yet long-standing challenge of neuroscience. With the advancement of several ground-breaking neurotechnological tools for studying neural circuits in an unprecedented spatio-temporal resolution, we have started to understand mechanisms underlying behaviour-dependent circuit dynamics and their alterations in brain disorders. Rodent models of neurodevelopmental disorders have provided an important tool to study dysfunctions at cellular, molecular and circuit levels as well (Banerjee et al. 2019 BRAIN). Our overall objective is to study neural correlates of complex cognitive behaviour and identify mechanisms that would allow us to study cognitive dysfunctions seen in neurodevelopmental disorders in the autism spectrum.
Data: CORDIS, © European Union
Project objective
Understanding the cellular and synaptic basis of memory remains a central goal of modern neuroscience. Physical traces of memory exist as an enduring, experience-dependent change in neural activity in response to learning. In the hippocampus, a key region of the mammalian brain involved in memory formation and recall, new neurons are continually generated in the dentate gyrus (DG) where they form an integral part of the existing functional circuitry. Despite its key position in the hippocampal formation, however, the function of DG and its adult-born neurons in vivo has not been carefully investigated. Here, by applying transgenic and optogenetic approaches – including multicolour genetically encoded activity reporters – together with longitudinal two-photon imaging, we aim to study functional dynamics and plastic changes in DG in health and disorder. We propose that activity patterns in DG cell populations show activity-dependent changes during learning and construct a cellular and circuit basis for contextual memory engrams. We will also investigate how synaptic alterations in excitation-inhibition balance and defects in adult neurogenesis in DG lead to neurological disorders such as Rett syndrome.
Original text from CORDIS.
Participants
- UNIVERSITAT ZURICH · ZurichCoordinatorSwitzerland
Links
Data: CORDIS, © European Union