Project Details
Projekt
The role of interneuron plasticity in the generation of fast local network oscillations
Applicant
Professor Dr. Jörg Geiger
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2014 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 245861656
Increasing evidence suggests that interneuron (IN) plasticity is contributing to the plasticity of micro-circuits in many brain regions. However, the functional importance of IN plasticity remains unknown. Here, we propose that long-lasting plasticity of IN excitation is a main mechanism regulating oscillatory brain activity especially in the gamma (g) frequency range (30-90 Hz). We will focus our research in this proposal exclusively on fast-spiking INs expressing the calcium binding protein parvalbumin (PV) in three brain regions: The hippocampal CA3, the presubiculum of the parahippocampal cortex and the M1 subregion of the motor cortex. This approach aims to clarify to which extent synaptic plasticity at one defined IN type could be attributed to a specific neuronal network function across brain regions. The central network function studied here is the generation of fast network oscillations. All experiments will be performed in acute brain slice preparations of the respective brain areas of mice using extracellular and whole-cell recordings. Oscillatory activity in vitro will be induced pharmacologically. Along these lines we could show in the 1st funding period of the research unit (RU) that in vitro g-oscillations in CA3 induce long-term potentiation (LTP) at excitatory synapses onto fast-spiking PV interneurons (PVIs). To probe whether PVI LTP could in turn enhance g-oscillations, we induced g-activity a second time 1h after the first induction. We discovered a potentiation of the second g-pattern. In subsequent experiments we could provide preliminary evidence that PVI LTP is involved in this form of ‘g-oscillation plasticity’. The central Aim here is to deepen the mechanistic analysis of these likely reciprocal interactions of PVI plasticity and g-oscillations and corroborate this hypothesis. In addition we will extent this analysis to the presubiculum and M1. Assuming the proposed reciprocal interactions of PVI plasticity and g-oscillations, we will use ‘g-oscillation plasticity’ as essay to test new molecular tools in the RU in collaboration with our partners (TP1 Bartos, TP5 Wulff) and their impact on interfering with PVI plasticity. The new molecular mechanisms will be identified by using this essay for differential RNA sequencing experiments and to identify PVI plasticity-related up-regulated transcripts. Finally, we will use this essay to identify transgenic disease models which have lost PVI plasticity. The results of this analysis will lead to new molecular hypothesis of PVI plasticity and support the development of new interference tools. Subsequent plasticity and connectivity analysis of promising animal models by using multi-patch-clamp recordings in close collaboration with TP3 Vida will identify changes of plasticity rules and morphological alterations in addition to changes in local network topology. The results obtained here may guide computational experiments (TP9 Sprekeler) and in vivo recordings in M1 (TP6 Poulet).
DFG Programme
Research Units
