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Deep brain imaging of cellular mechanisms of sensory processing and learning

Project description

Explaining learning-dependent changes at the neural network level

We constantly receive multiple stimuli from our surroundings. For the stimuli to be used effectively as information, perception, learning and memorising processes are necessary, which rely on structural and cellular mechanisms of plasticity in identified neural circuits. However, until now, the research on structural and cellular plasticity was limited to the cerebral cortex plasticity input. The EU-funded AXPLAST project aims to elucidate mechanisms of neuronal coding in multisensory integration and associative learning in deeper brain regions by combining a miniature microscopy imaging technique to map structural dynamics of defined neural circuits in the amygdala and its thalamic input areas. This will enable fundamental insights into the cellular mechanisms underlying sensory processing upon learning.

Objective

Learning and memory are the basis of our behaviour and mental well-being. Understanding the mechanisms of structural and cellular plasticity in defined neuronal circuits in vivo will be crucial to elucidate principles of circuit-specific memory formation and their relation to changes in neuronal ensemble dynamics.

Structural plasticity studies were technically limited to cortex, excluding deep brain areas like the amygdala, and mainly focussed on the input site (dendritic spines), whilst the plasticity of the axon initial segment (AIS), a neuron’s site of output generation, was so far not studied in vivo. Length and location of the AIS are plastic and strongly affects a neurons spike output. However, it remains unknown if AIS plasticity regulates neuronal activity upon learning in vivo.
We will combine viral expression of AIS live markers and genetically-encoded Ca2+-sensors with novel deep brain imaging techniques via gradient index (GRIN) lenses to investigate how AIS location and length are regulated upon associative learning in amygdala circuits in vivo. Two-photon time-lapse imaging of the AIS of amygdala neurons upon fear conditioning will help us to track learning-driven AIS location dynamics. Next, we will combine miniature microscope imaging of neuronal activity in freely moving animals with two-photon imaging to link AIS location, length and plasticity to the intrinsic activity as well as learning-related response plasticity of amygdala neurons during fear learning and extinction in vivo. Finally, we will test if AIS plasticity is a general cellular plasticity mechanisms in brain areas afferent to the amygdala, e.g. thalamus.

Using a combination of two-photon and miniature microscopy imaging to map structural dynamics of defined neural circuits in the amygdala and its thalamic input areas will provide fundamental insights into the cellular mechanisms underlying sensory processing upon learning and relate network level plasticity with the cellular level.

Host institution

DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV
Net EU contribution
€ 941 877,50
Address
VENUSBERG-CAMPUS 1/99
53127 Bonn
Germany

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Region
Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt
Activity type
Research Organisations
Links
Total cost
€ 941 877,50

Beneficiaries (2)