Throughout lifetime a proper balance between excitation and inhibition is crucial for a healthy brain. How exactly this balance between excitation and inhibition is regulated in the brain is not well understood. One intriguing possibility is that glutamatergic and GABAergic synaptic plasticity are not regulated separately, but somehow interact to maintain this balance. In the work proposed here we intend to examine whether plasticity of inhibitory and glutamatergic synapses interact with each other on a very local scale, i.e. within the dendrite. My research has two main objectives. (1) I ask whether excitation affects plasticity of inhibitory axons. I propose to examine at what spatial scale excitatory activity can affect turnover of GABAergic boutons. The area of activity manipulation will be systematically decreased (ranging from global manipulations to activation of individual dendritic inputs) and we will examine how these manipulations affect the formation and loss of GABAergic boutons at the site of manipulation. (2) I propose to examine how local inhibitory synaptic activity affects nearby plasticity of excitatory synapses. Potentiation at individual excitatory synapses will be induced by a glutamate uncaging protocol. A nearby inhibitory synapse (on the same dendrite) will be activated at specific intervals from the plasticity induction protocol and we will test whether this local inhibitory activity affects the induced excitatory plasticity. The proposed research involves the use of advanced imaging techniques, in combination with electrophysiology and using tools from molecular biology. The results of the proposed research will advance our understanding how the balance between excitation and inhibition in the brain is regulated. A better understanding of this crucial balance is fundamental to a wide variety of neuroscience disciplines, from computational and cellular neuroscience to clinical applications.
Fields of science
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Funding SchemeMC-ERG - European Re-integration Grants (ERG)
3584 CS Utrecht
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