Project description
Profiling inhibitory projections to hippocampal-entorhinal networks
The brain’s interconnected networks are carefully orchestrated to enable high-level functions. The hippocampus and entorhinal cortex are interconnected and play a role in learning and memory. The septum, a subcortical structure near the brain’s midline, sends inhibitory inputs to the hippocampal and entorhinal networks. These GABAergic neurons, named for the neurotransmitter they release, modulate neuronal spiking in hippocampal and entorhinal networks that supports spatial- and object-coding. These neurons are vulnerable to degeneration; moreover, medial septum inactivation is associated with cognitive impairments. Funded by the European Research Council, the VulnerableInhibition project aims to elucidate the role of the septal-entorhinal GABAergic projections in episodic memory and spatial navigation dysfunction and investigate mitochondrial dysfunction as a source of their enhanced vulnerability.
Objective
Septal GABAergic projection neurons are considered “pacemaker” cells as they enable the temporal organization of neuronal spike firing in hippocampal and entorhinal networks that support spatial- and object-coding. Accordingly, medial septum inactivation is associated with cognitive impairments, but the specific role of the septal-entorhinal GABAergic projections therein has remained unexplored. This is a pressing question, as we have evidence that septal GABAergic projections exhibit enhanced vulnerability. In mouse models with neurodegeneration, we found that septal GABAergic axons exhibit signs of degeneration when target cells in the entorhinal cortices are not yet impaired. Furthermore, we have evidence for mitochondrial pathology in the degenerating axons. These results prompt the following questions: How does malfunction of septal GABAergic projections translate into dysfunction of downstream networks involved in episodic memory and spatial navigation? What are the mechanisms that render septal GABAergic projections prone to vulnerability?
Employing in vivo electrophysiology combined with optogenetics, behavioral studies, 2-photon imaging of axons and mitochondria in live mice and spatial transcriptomics, we will tackle the following issues: (A) assess how impaired septal GABAergic projections affect spatial- and object-coding in the medial and lateral entorhinal cortex (MEC and LEC), (B) assess the functional consequence thereof on spatial and associative memory in the LEC (C) gauge putative cellular mechanisms, with focus on mitochondria, that render septal long-range GABAergic projections vulnerable and (D) identify genes/gene networks whose expression is involved in degeneration of septal GABAergic neuron axons. With these studies we will elucidate how septal neurons contribute to cognition, reveal common mechanisms for axonal degeneration, and ideally identify novel biomarkers and therapeutic targets for “mitochondropathies”.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- medical and health sciences basic medicine pathology
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2023-ADG
See all projects funded under this callHost institution
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
69120 Heidelberg
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.