The endoplasmic reticulum (ER) is an essential cellular organelle responsible for regulating intracellular calcium levels, translocating and secreting proteins, and coordinating organelle dynamics, among other functions. ER extends throughout the cell as a network of flattened sacs and tube-like structures, rearranging its functional domains according to cellular demands and establishing contact sites with other organelles to promote signalling and transfer resources. ER-mitochondria communication has been of particular interest, as it coordinates the mitochondrial calcium uptake (essential for energy production and cellular signalling), mitochondrial dynamics and lipid exchange. Disruption of normal ER function or ER-mitochondrial contacts has been associated with neurological disorders.
Neurons are highly polarised cells capable of quickly processing and transmitting information through electrical and chemical signals at specific sites - synapses. They have three main compartments: dendrites - branch-like processes that receive incoming signals in postsynaptic terminals and pass them to the cell body; cell body - responsible for processing information and maintaining the essential cellular functions; and axon - long extension with pre-synaptic terminals that send signals to other neurons further on the neuronal network. The communication occurring at synapses is not static; these connections can strengthen or weaken based on experience, a process called synaptic plasticity that is the basis for learning and memory. The dynamic nature of cellular organelles and synaptic proteins is essential to promote and support functional and structural adaptations underlying synaptic plasticity.
In dendrites, ER presents mainly a tubular morphology that may extend into dendritic spines (small protrusions where most excitatory synaptic transmission occurs), determining their responsiveness to synaptic activity. Activity-mediated dynamics of ER and mitochondria are necessary to uphold synaptic plasticity, and neuronal activity also increases ER-mitochondria contacts. However, studying these processes is challenging because synapses are small and tightly packed structures. Traditional imaging techniques have limitations in capturing the fine details of synaptic structures. Recent advancements in super-resolution microscopy have revolutionised our ability to visualise dynamic changes in living neurons. These techniques can offer unprecedented insight into the organisation and dynamics of dendritic ER and mitochondria upon synaptic activity and plasticity.
Hence, through the application of super-resolution microscopy techniques, this project aims to study how neuronal activity affects the organisation and dynamics of ER and its mitochondria contact sites, and to assess its functional significance for mechanisms of synaptic activity and plasticity.
