Cellular Neuroscience

Cellular neuroscience group is interested in cellular and molecular mechanisms underlying learning. Special focus has been in dendritic spines. Currently, group focuses on understanding how neuron activity regulates the spine initiation. In neuropathic pain, inflammation seems to induce learning-type changes in spinal cord neurons but loss of spines in the brain. Another aim of the group is to characterize the timeline and cellular mechanisms leading to these changes.

Dendritic spines are small protrusions in neuronal dendrites where the postsynaptic components of most excitatory synapses reside in the brain. Specific sets of new spines arise during new experiences or the acquisition of new skills, and provide the foundation for their retention. Consequently, defects in the regulation of dendritic spines are involved in many neurological diseases from memory disorders to psychiatric diseases. Furthermore, recent research has shown that spines are also involved in the “learning” of chronic pain.

Goal: We are aiming at a comprehensive understanding on how spine initiation is regulated in neurons. So far, four spine initiation factors have been identified. Our current research focuses on understanding how localization or expression of these spine initiation factors are regulated in neurons. Another aim is to understand cellular changes occurring during the formation of neuropathic pain. Using an arthritis mouse model, used also for pain studies, we will study the formation of such a pain, where the inflammation, whichcauses the primary pain, heals, but the pain remains. We want to understand how pain is stored and how ”learning” of the pain can be prevented.

Methods: We are taking a bottom-up approach, where molecular mechanisms learnt in simpler in vitro systems, such as test tubes, fibroblasts or dissociated hippocampal neurons, are taken to more complex systems, such as organotypic brain slices and the in vivo mouse brain. At all levels, advanced microscopy techniques play a major role.

Selected publications

Khanal P, Boskovic Z, Lahti L, Ghimire A, Minkeviciene R, Opazo P, Hotulainen P. (2023) Gas7 Is a Novel Dendritic Spine Initiation Factor. eNeuro. 10(4):ENEURO.0344-22.2023.

Bertling E, Blaesse P, Seja P, Kremneva E, Gateva G, Virtanen MA, Summanen M, Spoljaric I, Uvarov P, Blaesse M, Paavilainen VO, Vutskits L, Kaila K, Hotulainen P*, Ruusuvuori E*. (2021) Carbonic anhydrase seven bundles filamentous actin and regulates dendritic spine morphology and density. EMBO Rep.22:e50145. *PH and ER contributed equally to this work as senior authors

Abouelezz A, Stefen H, Segerstråle M, Micinski D, Minkeviciene R, Lahti L, Hardeman EC, Gunning PW, Hoogenraad CC, Taira T, Fath T, Hotulainen P. (2020) Tropomyosin Tpm3.1 Is Required to Maintain the Structure and Function of the Axon Initial Segment. iScience 23:101053.

Minkeviciene R, Hlushchenko I, Virenque A, Lahti L, Khanal P, Rauramaa T, Koistinen A, Leinonen V, Noé FM, Hotulainen, P. (2019) MIM-Deficient Mice Exhibit Anatomical Changes in Dendritic Spines, Cortex Volume and Brain Ventricles, and Functional Changes in Motor Coordination and Learning. Frontiers in Mol. Neurosci. 12, 276.

Hlushchenko I, Khanal P, Abouelezz A, Paavilainen VO, Hotulainen P. (2018) ASD-Associated De Novo Mutations in Five Actin Regulators Show Both Shared and Distinct Defects in Dendritic Spines and Inhibitory Synapses in Cultured Hippocampal Neurons. Front Cell Neurosci.12:217.

Bertling, E., Englund, J., Minkeviciene, R., Koskinen, M., Segerstråle, M., Castren, E., Taira, T. and Hotulainen, P. (2016) Actin Tyrosine-53-Phosphorylation in Neuronal Maturation and Synaptic Plasticity. J. Neuroscience.36, 5299-5313.

Saarikangas, J., Kourdougli, N., Senju, Y., Chazal, G., Segerstråle M., Kuurne, J., Minkeviciene, R., Mattila, P.K., Garrett, L., Hölter, S.M., Becker, L., Racz, I., Hans, W., Klopstock, T., Wurst, W., Zimmer, A., Fuchs, H., Gailus-Durner, V., Hrabě de Angelis, M., von Ossowski, L., Taira, T., Lappalainen, P., Rivera, C. and Hotulainen, P. (2015) MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation. Dev. Cell. 33, 644-659. Cited 59.

Koskinen, M., Bertling E., Hotulainen, R., Tanhuanpää, K. and Hotulainen, P. (2014) Myosin IIb controls actin dynamics underlying the dendritic spine maturation. Mol. Cell. Neurosci. 61C, 56-64. Cited 36.

Hotulainen, P., and Hoogenraad, C.C. (2010) Actin in dendritic spines: connecting dynamics to function. J. Cell Biol. 189, 619-629. Cited 605.

Hotulainen, P., Llano, O., Smirnov, S., Tanhuanpää, K., Faix, J., Rivera, C., Lappalainen, P. (2009) Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis. J. Cell Biol. 185, 323-339. Cited 257.

External funding

Medicinska understödsföreningen Liv och Hälsa r.f.
Sigrid Jusélius Foundation

Follow

Group’s own website: http://www.hotulainenlab.fi
ResearchGate: Pirta Hotulainen
Reseacher-ID: B-8874-2015
ORCID: 0000-0003-0764-8582
X: @PirtaHotulainen