Effects of Rab3a-Interacting Molecule 1a (RIM1a), linked to the enhancement of cognitive function, on presynaptic function and plasticity: a direct link from genes to cognition? (360G-Wellcome-203795_Z_16_A)

Neurons communicate with each other via specialised junctions called synapses. The brain contains trillions of synapses where information is transferred and processed, which shapes neuronal network and brain function. Synaptic terminals contain small vesicles filled with neurotransmitters. When a nerve impulse invades the synaptic terminal, it triggers fusion of synaptic vesicles with the plasma membrane and release of transmitter molecules. Neurotransmitters quickly diffuse towards the target neuron, where they bind to specific receptors and evoke further electrical or chemical signalling. Very often mutations in proteins that regulate synaptic vesicle fusion lead to neurological disorders and cognitive impairment. RIM1alpha is one of the key proteins that regulate synaptic release of neurotransmitters by bringing together the key components of release machinery. Recently, a novel mutation in RIM1alpha was discovered that enhances cognitive function in humans. This "experiment of nature" represents a unique model to test how alterations in synaptic function shape high-level brain activity and cognition. In this project we aim to understand the effects of this RIM1alpha mutation in mouse neuronal model on synaptic transmission and use-dependent synaptic plasticity. We anticipate that our results will provide novel unparalleled insights into the cellular mechanisms that underlie cognitive processing in the brain.