Periodic Reporting for period 1 - CIRCA3 (Synaptic computations of the hippocampal CA3 circuitry)
Berichtszeitraum: 2022-01-01 bis 2023-12-31
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.
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.
In this project, I have performed multicellular patch clamp analysis to record the properties of individual cells in the CA3 circuit. I have characterized the properties of distinct subclasses of inhibitory an excitatory neurons in CA3. In addition, I have studied information transfer in this circuit, observing the arrangement of synaptic connections between neurons, and the properties of these connections. We record how patterns of activity that occur in the brain during behaviour will pass between the cells in this circuit, to understand how information is processed and stored in the hippocampal CA3 area.
In this project, we identified subclasses of neurons in CA3 with distinct properties and wiring, showing the importance of brain cell diversity for its function. We demonstrate that the CA3 circuit, long considered a key site for memory storage, has far greater network complexity than previously considered. This is important not only for understanding how this brain area works, but shows how connectivity at the single cell level is important more broadly for our understanding of the brain. In addition, we observed the properties of connections between excitatory and inhibitory neurons in CA3, allowing understanding of how information flows through this circuit. These results fill an important knowledge gap in our understanding of hippocampal function, and are an important step in moving towards understanding how the brain works across levels (synapses, cells, circuits). Characterising how the circuit function is essential to understanding what goes wrong in disease. As the hippocampus is an important player in epilepsy, this research will aid our future understanding of disease pathology. Finally, this fellowship has allowed me (the researcher) to acquire expertise in advanced electrophysiology techniques, and been a key step in my development as a future neurophysiology researcher. This training will therefore continue to be of value, facilitating continuing the high-quality research that is essential to understanding our most complex organ.