This proposal addresses one of the most profound determinants of brain function and cognition: how is the brain affected by a stimulus that is novel and is therefore potentially significant? The proposal, centred around the auditory system, will decipher the pathways that start with the detection of a novel stimulus and lead through a cascade of inter-related signals to the induction of the synaptic plasticity. We hypothesize that a novel sensory stimulus is detected by the conjunction of the sensory activity it evokes in cortex with inputs from the neurotransmission systems.
This conjunction activates electrophysiological novelty responses and the associated expression of immediate-early genes (IEGs). The IEGs can be used to identify network components within auditory and motor cortices that sub-serve sound frequency discrimination in the behavioural training cortex. They orchestrate changes in the profiles of gene expression, alternative splicing and microRNAs leading to synaptic modifications that ultimately change the animal behaviour. To test this model we will study novelty detection using three different readouts: behavioural, electrophysiological and molecular. Genetic engineering manipulations and molecular techniques will be used to assess the relationships between these readouts. Brain disorders such as schizophrenia are associated with abnormal sensory gating of novel vs non-novel stimuli. The expression of such pathologies requires interactions between environmental, electrophysiological and molecular mechanisms.
The NovelTune teams aim to link these various processes and elucidate the underlying mechanisms through an interdisciplinary strategy. The network integrates strong expertises including state-of-the-art and high throughput gene expression technologies and the most advanced bioinformatics competence. The combination of these powerful methods is expected to yield profound insights into the cascade of events underlying the processing of novelty.
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