Cellular Neuroscience

The Cellular Neuroscience group investigates the cellular and molecular mechanisms underlying learning, with a special focus on dendritic spines. Dendritic spines are small protrusions on neuronal dendrites where the postsynaptic components of most excitatory synapses in the brain are located. These spines play a critical role in learning and memory, as new spines form during experiences or skill acquisition, serving as a foundation for their retention. Dysregulation of dendritic spines is linked to various neurological conditions, including memory disorders and psychiatric diseases. The group aims to comprehensively understand how spine initiation is regulated in neurons.

An additional area of focus is the relationship between peripheral inflammation and learning and memory. While acute or chronic inflammation’s immediate effects on the brain are relatively well understood, it remains unclear whether resolved inflammation leaves lasting changes in the brain. The group explores the long-term consequences of peripheral inflammation on cognitive processes and identifies the specific cells involved in these changes.

To address these questions, the Cellular Neuroscience group employs a rheumatoid arthritis mouse model (CAIA). Through a combination of behavioral analyses, advanced imaging, cytokine measurements, and electrophysiology, the group evaluates how inflammation shapes brain function over time.

This research seeks to redefine our understanding of how transient inflammation impacts long-term brain health. The findings may inform improved treatment strategies for inflammation-associated neurological conditions and highlight the importance of anti-inflammatory lifestyles. By uncovering the mechanisms behind inflammation-driven brain changes, this work holds potential for advancing therapies for diseases such as rheumatoid arthritis, Alzheimer’s, and long covid.

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

Micinski D, Hotulainen P. Actin polymerization and longitudinal actin fibers in axon initial segment plasticity. Front Mol Neurosci. 2024; 17:1376997.

Khanal P, Boskovic Z, Lahti L, Ghimire A, Minkeviciene R, Opazo P, Hotulainen P. Gas7 Is a Novel Dendritic Spine Initiation Factor. eNeuro. 2023; 10: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*. Carbonic anhydrase seven bundles filamentous actin and regulates dendritic spine morphology and density. EMBO Rep. 2021; 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. Tropomyosin Tpm3.1 Is Required to Maintain the Structure and Function of the Axon Initial Segment. iScience. 2020; 23:101053.

Minkeviciene R, Hlushchenko I, Virenque A, Lahti L, Khanal P, Rauramaa T, Koistinen A, Leinonen V, Noé FM, Hotulainen, P. 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. 2019; 12:276.

Hlushchenko I, Khanal P, Abouelezz A, Paavilainen VO, Hotulainen P. 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. 2018; 12:217.

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

Saarikangas J, Kourdougli N, Senju Y, Chazal G, Segerstråle M, Kuurne J, Minkeviciene R, Mattila PK, Garrett L, Hölter SM, 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 O, Hotulainen P. MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation. Dev Cell. 2015; 33:644-659.

Hotulainen P, Hoogenraad CC. Actin in dendritic spines: connecting dynamics to function. J Cell Biol. 2010; 189:619-629.

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

External funding

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

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ResearchGate: Pirta Hotulainen
Reseacher-ID: B-8874-2015
ORCID: 0000-0003-0764-8582
X: @PirtaHotulainen
Bluesky: @pirtahotulainen.bsky.social