Pirta Hotulainen group
Regulation of the actin cytoskeleton in dendritic spines
|Pirta Hotulainen, PhD
P.O. Box 56, FI-00014 University of Helsinki
Phone: +358 9 191 57606
Fax: +358-9-191 57620
The human brain consists of hundred billion neurons interconnected into functional neuronal circuits that underlie all our behaviors, thoughts, emotions, dreams and memories. The capacity of neurons to function within neuronal circuits is mediated via specialized cell junctions called synapses. Chemical synapses regulate the electric communication within neural networks and pass information directly from presynaptic axon terminals to postsynaptic dendritic regions. Precise control of the development and connectivity of synapses is critical for accurate neural network activity and normal brain function. Most excitatory synapses in the mammalian brain are formed at tiny dendritic protrusions, named dendritic spines (Bourne and Harris, 2008). Experimental evidence has shown that changes in spine morphology account for functional differences at the synaptic level (Kasai et al., 2003; Yuste and Bonhoeffer, 2001). It is now widely believed that information in the brain can be stored by strengthening or weakening existing synapses, as well as appearance or disappearance of dendritic spines, which subsequently leads to the formation or elimination of synapses. These functional and structural changes at spines and synapses are believed to be the basis of learning and memory in the brain (Kasai et al., 2010). During the last decade, numerous studies on signaling pathways demonstrated that the actin cytoskeleton plays a pivotal role in the formation and elimination, motility and stability, and size and shape of dendritic spines (reviewed in Hotulainen and Hoogenraad, 2010). In addition, modulation of actin dynamics drives the morphological changes in dendritic spines that are associated with alteration in synaptic strength (Cingolani and Goda, 2008). It has also been shown that various memory disorders involve defects in the regulation of the actin cytoskeleton (Newey et al., 2005).
The main goal of our group is to elucidate the mechanisms of actin cytoskeleton regulation in dendritic spines and to reveal how regulation of cytoskeletal dynamics affects dendritic spine development, morphology and plasticity. Currently, we are studying the regulation of dendritic spine structural and functional plasticity from three different aspects. First, we are studying the roles of different actin-binding proteins. Second, we are studying the effects of a novel mechanism of actin regulation -actin phosphorylation. Third, we are studying the effects of intracellular pH. We have already shown that these regulatory mechanisms affect the actin treadmilling rate. Next, we will examine how that affects dendritic spine morphology, motility and synapse function. As model systems, we use cultured rat primary hippocampal neurons and living mice or rats. Spine morphology and motility, as well as actin dynamics in spines, are analyzed by using various microscopy techniques. In addition, we use electrophysiological approaches to study the role of actin regulation in neuron function. These studies will result in a comprehensive understanding on regulation of dendritic spine structural plasticity. This knowledge is fundamental in understanding cognitive processes such as learning as well as neurological diseases.