Periodic Reporting for period 2 - PreSynPlast (Molecular mechanisms of presynaptic plasticity)
Período documentado: 2022-03-01 hasta 2023-08-31
We aim to better understand the mechanisms of learning and memory. From newborn to elderly, learning and memorizing is essential for our lives. Impairments in learning and memory have immense implications for the society.
An important mechanism of learning and memory is synaptic plasticity. During synaptic plasticity the neurotransmitter release of the presynaptic cell and the response to the neurotransmitter of the postsynaptic cell can be altered. In particularl, the presynaptic mechanisms of synaptic plasticity are poorly understood. To investigate the presynaptic mechanisms we develop techniques that allowed to measure the function of the presynaptic nerve terminal more directly. We use tiny glass pipettes and position the tip of the pipette onto the nerve terminals to measure its function. In addition, we use super-resolution microscopic, genetic, and computational techniques to analyze the structural and functional changes in the presynaptic terminals.
An important mechanism of learning and memory is synaptic plasticity. During synaptic plasticity the neurotransmitter release of the presynaptic cell and the response to the neurotransmitter of the postsynaptic cell can be altered. In particularl, the presynaptic mechanisms of synaptic plasticity are poorly understood. To investigate the presynaptic mechanisms we develop techniques that allowed to measure the function of the presynaptic nerve terminal more directly. We use tiny glass pipettes and position the tip of the pipette onto the nerve terminals to measure its function. In addition, we use super-resolution microscopic, genetic, and computational techniques to analyze the structural and functional changes in the presynaptic terminals.
We established direct patch-clamp recordings from small conventional nerve terminals of neurons. We found significant differences in the short-term plasticity of the duration of action potentials in excitatory and inhibitory nerve terminals. We also uncovered several other mechanisms of presynaptic function such as the calcium-sensitivity of vesicle fusion and ectopic action potential initiation in axons of dopaminergic neurons.
The established technique of direct presynaptic patch clamp recordings from small conventional excitatory and inhibitory nerve terminals allows to analyze presynaptic function with unprecedented temporal resolution. We will combine these techniques with special microscopic techniques (super resolution microscopy). Ultimately, we aim to reveal molecular pathways of presynaptic plasticity that are relevant in health and disease.