Descrizione del progetto
Spiegare i cambiamenti dipendenti dall’apprendimento a livello di rete neurale
Riceviamo costantemente molteplici stimoli dall’ambiente circostante. Affinché tali stimoli possano essere utilizzati efficacemente come informazioni, sono necessari processi di percezione, apprendimento e memorizzazione che si basano su meccanismi strutturali e cellulari di plasticità nei circuiti neurali identificati. Finora, tuttavia, la ricerca sulla plasticità strutturale e cellulare si è limitata all’input di plasticità della corteccia cerebrale. Il progetto AXPLAST, finanziato dall’UE, intende chiarire i meccanismi di codifica neuronale nell’integrazione multisensoriale e nell’apprendimento associativo nelle regioni cerebrali più profonde, combinando una tecnica di imaging con microscopia miniaturizzata per mappare le dinamiche strutturali di circuiti neurali definiti nell’amigdala e nelle sue aree talamiche di ingresso. Ciò consentirà di comprendere a fondo i meccanismi cellulari alla base dell’elaborazione sensoriale e dell’apprendimento.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
53127 Bonn
Germania