Investigations on pre- and postsynaptic plasticity

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Nearly five decades after the inital discovery of long-term potentiation (LTP), innumerable studies investigating long-lasting increases and decreases (LTD) in synaptic efficacy have been published. Over the years, the synaptic plasticity and memory (SPM) hypothesis has emerged stating that synaptic alterations underly memory formation and learning since pharmacological or genetic manipulation of key players in synaptic plasticity affected memory performance in behavioural tests. Moreover, long-term modulations at synapses, have been closely linked to changes in synapse number and morphology. Increased numbers of dendritic spines or boutons have been detected following learning. In summary, there is profound evidence that synaptic plasticity and synapse morphology correlate with learning and memory formation.However, a direct link between synaptic changes and phases of learning or memory is challenging to establish due to1) a lack of tools that can specifically block synaptic plasticity without affecting basal neurotransmission and2) the complexity of studying synaptic alterations in behaving animals.Beyond the fundamental importance of understanding synaptic function and how it is related to neuronal network and behaviour, these relationships are of relevance to human health because impaired synaptic plasticity and synapse loss has been associated with a variety of neurodegenerative diseases.My DPhil research focusses on investigating the role of synapses in learning, memory and behaviour on the molecular as well as the network level.My DPhil research can be divided in two major parts:1) I aim to investigate presynaptic mechanisms since they are poorly established compared to their postsynaptic counterparts but play just as an important role in learning and memory. This includes to characterize the mechanisms of preNMDAR activation at the presynaptic and terminals of Schaffer-collateral synapses.2) I aim to develop a fiber-based system for minimally invasive deep-brain imaging in vivo. With this technique, we will be able to directly observe synaptic changes in the behaving animal with minimal constriction.