Abstract
Tropomyosin (Tpm) has been regarded as the master regulator of actin dynamics. Tpms regulate the binding of the various proteins involved in restructuring actin. The actin cytoskeleton is the predominant cytoskeletal structure in dendritic spines. Its regulation is critical for spine formation and long-term activity-dependent changes in synaptic strength. The Tpm isoform Tpm3.1 is enriched in dendritic spines, but its role in regulating the synapse structure and function is not known. To determine the role of Tpm3.1, we studied the synapse structure and function of cultured hippocampal neurons from transgenic mice overexpressing Tpm3.1. We recorded hippocampal field excitatory postsynaptic potentials (fEPSPs) from brain slices to examine if Tpm3.1 overexpression alters long-term synaptic plasticity. Tpm3.1-overexpressing cultured neurons did not show a significantly altered dendritic spine morphology or synaptic activity. Similarly, we did not observe altered synaptic transmission or plasticity in brain slices. Furthermore, expression of Tpm3.1 at the postsynaptic compartment does not increase the local F-actin levels. The results suggest that although Tpm3.1 localises to dendritic spines in cultured hippocampal neurons, it does not have any apparent impact on dendritic spine morphology or function. This is contrary to the functional role of Tpm3.1 previously observed at the tip of growing neurites, where it increases the F-actin levels and impacts growth cone dynamics.
Highlights
Most synapses between excitatory neurons form on dendritic spines, which are protrusions from dendrites that consist of a large, actin-rich head separated from the dendrite shaft by a thin neck
We examined the effect of Tpm3.1 overexpression on dendritic spine morphology and synapse function using transgenic mice that express hTpm3.1
Previous studies showed hTpm3.1 overexpression increases the size of actin-rich growth cones at the tip of growing neurites and the amount of filamentous actin (F-actin) present in growth cones [22]
Summary
Most synapses between excitatory neurons form on dendritic spines, which are protrusions from dendrites that consist of a large, actin-rich head separated from the dendrite shaft by a thin neck. Actin exists in multiple populations in dendritic spines, with different functions and rates of turnover [1]. Most actin present in spines is dynamic and can change its organisation very rapidly [2]. The development and plasticity of dendritic spines are reliant on the flexibility of the actin cytoskeleton. The most studied cellular model of synaptic plasticity is long-term potentiation (LTP). In LTP, high-frequency stimulation causes a signalling cascade that leads to insertion of AMPA receptors, enlargement of dendritic spines, an increase in synaptic strength [3], and polymerisation of actin [4]
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