Dendritic spines are the principal target of excitatory synaptic input in the mammalian forebrain. While the Postsynaptic Density (PSD) is the most prominent component of a spine, the internal structure of spines is considerably more complex than once supposed: spine size and shape can be dynamically regulated, especially via activity, implying complex signaling pathways between the synapse and the actin cytoskeleton within the spine. Accumulating evidence suggests that proteins that regulate the actin cytoskeleton also help to regulate synaptic efficacy. Biochemical mechanisms underlying actin remodeling have been studied extensively in model systems, but little is known of the organization of the actin-binding proteins that mediate remodeling in dendritic spines. Activity-dependent remodeling of the actin cytoskeleton has recently emerged as a major cellular mechanism controlling postsynaptic function, but the nature and organization of the molecular machinery that orchestrates actin reorganization in spines remains obscure.
A broad variety of neuropsychiatric disorders are associated with specific patterns of spine disruption and abnormal spine structure, including Fragile X, Down?s, Williams syndrome, schizophrenia, or chronic administration of psychostimulants (like cocaine and amphetamine). To understand the pathophysiology of these defects we must first gain an understanding of spine function at a molecular level, pointing to the importance of a more detailed understanding of dendritic spines. Elucidating the architecture of the actin cytoskeleton and the organization of actin-binding proteins within the spine is my long-term goal. I would like to further define the microanatomy of spines and determine how the dynamic morphology of spines subserves neuronal plasticity.
Funding Sources: Hungarian Scientific Research Fund
Open position: PhD student