CIRCA3 · Synaptic computations of the hippocampal CA3 circuitry
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2022-01-01 → 2023-12-31
- EU contribution
- €174,167
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Synaptic computations of the hippocampal CA3 circuitry
Our brains have incredible powers of information processing, allowing us to understand and interact with the world around us, and to learn and store this information for the future. However the brain is also an incredibly complex organ, formed of billions of neurons, interconnected by synapses, therefore understanding the brain’s processing is an incredibly challenging task. As are we currently unable to explain the brain’s actions, we are also unable to understand how things go wrong in neurological disorders, therefore extensive research into this ‘last frontier’ in human physiology is critically needed. The incredible functions of the brain arise from continuous electrical activity passing through specific cells in the tangle of neural circuitry. Understanding the brain’s mechanisms of information processing therefore requires measurement and characterization of how the connections between neurons are arranged, and the properties of their communication. Here, we aim to determine the arrangement and properties of connections between neurons in the CA3 area of the hippocampus, a critical brain area for memory storage. Neurons have diverse cell types, meaning that the properties of cells and networks are highly heterogeneous, adding complexity to both the brain’s processing and our investigation. By recording the properties of multiple individual neurons at high resolution simultaneously, we determine ‘wiring rules’ for this brain area at the level of single cells. We aimed to use this approach to understand the basic processing units of the hippocampus, so we can begin to understand how activity flows through this brain area, and how this information flow can give rise to learning and memory.
Data: CORDIS, © European Union
Project objective
The hippocampus is critical for learning and memory, and the unique wiring of its CA3 area has inspired theories for neuronal mechanisms of memory storage and retrieval. CA3 pyramidal neurons form an interconnected network which could store unique experiences in specific ensembles of coactive cells. While an attractive hypothesis, many critical facets of CA3 networks remain unknown. CA3’s principal synaptic input arrives from dentate gyrus granule cells, via the powerful mossy fibre synapse. Little is known about the connectivity of individual granule cells to CA3 neurons, while their activity in vivo is very sparse, and they appear to predominantly target inhibitory interneurons rather than pyramidal neurons. Therefore, due to the technical challenge of identifying functionally connected neurons, whether the circuit properties of CA3 are sufficient for its proposed memory function is unclear. This project aims to determine the circuit mechanisms underlying information processing in CA3 at the level of individual synaptic connections. It will employ simultaneous multicellular patch-clamp recordings from CA3 neurons to identify locally connected neuronal ensembles in hippocampal slices, while driving sparse granule cell input in realistic activity patterns using optogenetic stimulation. This project will determine the synaptic connectivity of individual mossy fibre inputs into CA3 cell ensembles, characterise the role of feedforward inhibition in controlling pyramidal neuron activity, and reveal how the unique properties of each synaptic connection contributes to signal processing. Together, this study will provide an insight into the synaptic mechanisms of the hippocampus’ critical memory storage functions. The fellowship will facilitate rigorous scientific development of the researcher, including critical training in state-of-the-art circuit investigation techniques that will enable pursuit of an innovative research career, defined by the highest quality science.
Original text from CORDIS.
Participants
- INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA · KlosterneuburgCoordinatorAustria
Links
Data: CORDIS, © European Union