Cellular Neuropharmacology

Group 14
Leader: János Szabadics

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 (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.

Using direct patch clamp recordings and voltage-sensitive dye/protein imaging of 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 morphological analysis and immuno-labelling. By pulling outside out patches from small axons, we can understand the underlying ion-channel mechanisms of their firing. Furthermore, combination of axonal recordings with imaging of GEVI signals (genetically encoded voltage indicators) allows the measurement of the unitary synaptic responses, similarly to classical paired recording. We adapted bouton attach recording for small axons to precisely evoke and see individual spikes in single presynaptic neurons and link these to mono-synaptic responses. Using additional 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 implemented.

The research group is currently supported by the European Research Council (ERC-CoG Grant).

Excerpt from the Guidebook of the Institute 2015.

For further information please visit webpage of the group.

Lab members:

Antónia Arszovszki Research Fellow
János BrunnerResearch Fellow
Gyula MaloveczkyUndergraduate Student
Endre MarosiUndergraduate Student
Eszter SiposResearch Fellow
János SzabadicsGroup Leader
Andrea Anna SzabóTechnician
Gergely TarcsayJunior Research Fellow