IMAGING LEARNING

Linking hippocampus-dependent discriminative learning to hippocampal neuronal ensemble separation using Arc/Homer1a FISH imaging

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 Obiettivo del progetto (Objective)

'Association between neural representations of stimuli is believed to be an elementary mechanism for learning. However, the ability to prevent inappropriate associations by separating stimuli into coherent subgroups is no less important. Environment exploration triggers immediate-early gene (IEG) expression in environment-specific hippocampal ensembles, suggesting that distinct contexts are represented by distinct neural ensembles. Fluorescence in situ hybridization (FISH) to two IEGs, Arc and Homer1a is used to map neural activity during two different time epochs. This project will use the Arc/Homer1a FISH imaging to test if discrimination training enhances separation between neural ensembles. Contextual fear discrimination task compares the amount of freezing in a context in which fear conditioning had occurred to freezing in a lure context. Pre-exposure to the conditioning context enhances discrimination of similar contexts. Does it also enhance the ensemble separation? Navigation defined by stable distal cues on a continuously rotating arena requires discrimination of environmental stimuli into two coherent subsets. Does navigation training on the rotating arena enhance separation between neural ensembles representing room and arena stimuli? A hallmark cognitive deficit in schizophrenia is difficulty to process and use contextual information. Animal model of schizophrenia by systemic administration of a non-competitive NMDA receptor antagonist dizocilpine maleate also shows deficit in navigation on the rotating arena. Arc/Homer1a FISH will be used to test if ensemble separation is impaired in the schizophrenia model on the background of the discrimination tasks. The major objectives of this proposal are 1) to test if neural ensemble separation may be the basis for behavioral discrimination; 2) to test if neural ensemble separation is impaired in a model of schizophrenia; 3) to introduce the Arc/Homer1a FISH imaging of neural activity at two time points.'

Introduzione (Teaser)

Coherent learning requires that data from stimuli must be separated according to relevance to the situation. EU funding has helped to shed light on activity of different populations of nerve cells in separate tasks and applied this to a schizophrenia model.