The title of my talk: Activity-dependent and -independent spine initiation and learning

Abstract: Our current view is that short-term changes in memory can be achieved through changes in synaptic strength but to achieve long-term memories, new dendritic spines are needed. Dendritic spines are small protrusions along the neuronal dendrites where excitatory synapses are located. Strength and stability of a synapse depend on the size and stability of a dendritic spine. Number and functionality of synapses underlie all brain functions. In our previous study, we identified a protein called MIM as a spine initiation factor (Saarikangas et al., 2015). We have continued this line of research and identified and characterized other proteins, which initiate dendritic spines. So far, we have focused on spine initiation during development, which may or may not be activity-dependent. However, especially in the context of learning, it is very relevant to ask, whether spine initiation can be regulated by neuron activation (Bertling and Hotulainen, 2017). Based on our recent results, it seems that different spine initiation factors are differently regulated. Some of them are continuously active and facilitate continuous spine initiation in a random fashion. Other initiation factors are specifically activated by neuron activation, and I expect that this activation can be restricted in location to specific sites on the dendrite. I hypothesize that these both mechanisms are required to facilitate proper learning and formation of long-term memory.

Biography:  Dr. Pirta Hotulainen is the leader of the Cellular Neuroscience group at the Minerva Foundation Institute for Medical Research in Helsinki, Finland. Throughout her career Dr. Hotulainen has been interested in the regulation of the actin cytoskeleton and how this affects cell function. Dr. Hotulainen obtained her PhD in 2002 at University of Münster, Germany, in Prof. Martin Bähler’s lab. The goal of her PhD work was to characterize the role of a novel actin binding protein called SWAP-70. These studies led to exciting discovery of novel type of actin filaments. During her post-doctoral training, she wanted to learn more about the actin cytoskeleton regulation. Therefore, she joined the laboratory of Prof. Pekka Lappalainen at Institute of Biotechnology, University of Helsinki, Finland. In this group, Dr. Hotulainen did several projects to obtain wide perspective on actin regulation, starting with studies describing the fundamental roles of ADF/cofilins on various cellular processes. Next, she demonstrated how thick, contractile, actin filament bundles called stress fibers assemble in cells. By her third post-doc project, Pirta started her own research direction by bringing her actin cytoskeleton expertise from fibroblasts to neurons. On that direction, she started her own group in 2009 at Neuroscience Center, University of Helsinki. From the results of this project, we are now able to infer how actin cytoskeleton facilitates the dendritic spine formation and maturation.

Research Interests: A typical neuron possesses a cell body, dendrites, and an axon. The axon initial segment (AIS) is the site of action potential initiation and the boundary between the axonal and somatodendritic compartments. The signal sent by an axon is transmitted onto dendrites via synapses. On dendrites, most excitatory synapses are located in small protrusions called dendritic spines. Precise control of the dendritic spine morphology and density as well as the structure, length and location of AIS are critical for normal brain function. Accordingly, both aberrant spine morphology and non-functional AIS are linked to many neurological diseases. Actin cytoskeleton is a structural element underlying proper morphology of dendritic spines and proper structure of the AIS. The aim of Dr. Hotulainen´s research is to elucidate the mechanisms of actin cytoskeleton regulation in dendritic spines and in AIS. In addition, the group studies the mutations in actin regulating genes associated to autism spectrum disorder or schizophrenia to improve the understanding of the cellular defects underlying these diseases. So far, the group led by Dr. Hotulainen has elucidated the molecular mechanisms underlying dendritic spine initiation, dendritic filopodia elongation, spine head growth and spine head maintenance. Group also showed that lack of protein called MIM, causing improved dendritic spine initiation, decreased the frequency of mEPSCs in Purkinje neurons and MIM null mice displayed defects in motor coordination. Recently, the group discovered novel actin regulation mechanism –actin phosphorylation. They revealed that actin phosphorylation plays an important role in neuronal maturation and formation of the long-term potentiation