témavezető: Szabadics János
helyszín (magyar oldal): SE DI helyszín rövidítés: SE DI
A kutatási téma leírása:
The current theories of the broader hippocampal network explain its memory functions based on the firing of individual neurons. For example, the sparse activity of dentate gyrus granule cells (DG GC) codes and relays very specific information about the local environment. However, the mechanisms that generate the information-rich GC activity are elusive, because the firings of neurons, which project to and activate GCs, are usually dense and codes different aspects of the ongoing and previous experiences. The translation of diverse inputs into highly different specific codes appears to be one of the most fundamental neuronal computation rules throughout the brain. Therefore, we must understand the principles that govern how single GCs extract information from the activity of single upstream neurons. The fact that our knowledge about the GC output is much more advanced than the excitatory drives to the GCs, are in large part due to the mechanistic insights that were gained by the direct recording techniques from the unusually large axon terminals of the GCs. Therefore, to understand the excitation of GCs at a similar, we directly record from small axon terminals that excite GCs by further improving the sophisticated axonal recordings.
By direct patch clamp recordings from single small axon terminals we investigate the functional contributions of the axonal excitability properties of the four major glutamatergic inputs to the DG region. These include the two types of perforant paths (PPs) that originate from the Lateral and Medial Entorhinal Cortices. The medial PP convey spatial context, such as the famous grid cell activity. Whereas the lateral PP sends specific information content, for example certain objects. Inputs from hilar mossy cells distinguishes subtle differences and the most proximal glutamatergic synapses, from the hypothalamic supramammillary nucleus helps synchronizing (theta) GC activities during attention. Our goal is to better understand how the different excitability and synaptic properties of the individual axons of these four pathways contribute to the generation of specific GC activities.
Direct electrophysiology methods give several advantages. With whole bouton recordings, we can measure fundamental signaling properties, including the exact spike shape, which is important for how much calcium enters and how reliable is the subsequent synaptic release. Or we can also observe the plasticity of spike shapes during physiological activities. We identify the recorded axons with posthoc immuno-labelling. Furthermore, by pulling outside out patches from small axons, we can understand the underlying ion-channel mechanisms of their firing. With recordings from individual small axons in their target area, we can also directly measure the unitary synaptic responses, similarly to classical paired recording, by substituting the distal presynaptic soma recordings. We adapted bouton attach recording for small axons to precisely evoke and see individual spikes in single presynaptic neurons and link these to monosynaptic responses. Using several control methods we make sure that the recorded signals are correct and not contaminated by the influence of the recording pipettes, including voltage sensitive dye imaging and simulations, where the axonal structure, ionic conductances and also the recording instruments are accurately modelled.
Jelentkezési határidő: 2022-09-30
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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