Current lines of research:
ARC as a molecular hub for decoding long-term synaptic plasticity
How does ARC work?
ARC is the product of an immediate early gene and a multifunctional protein implicated in diverse forms of synaptic plasticity, postnatal cortical development, and memory formation. ARC functions as a protein interaction hub linking synaptic activity, intracellular trafficking, and gene expression programs with both synaptic and nuclear roles. It self-associates to form stable oligomers, including retrovirus-like capsids that mediate intercellular signaling.
Our work aims to elucidate ARC trafficking, assembly, and molecular functions, and to apply this knowledge to decode how plasticity is logically implemented at the neural systems level.
Decoding the molecular logic of ARC is increasingly relevant to brain disease. ARC signaling and plasticity mechanisms are implicated in Alzheimer’s disease, neurodevelopmental disorders, and substance use disorders.
Gene expression regulation and translational control of synaptic plasticity
How are specific forms of translation orchestrated at synapses?
Previous work has identified BDNF as a key trigger for transcription- and translation-dependent synaptic plasticity in the adult brain. Current studies focus on mechanisms of selective mRNA translation in vivo, including activity-dependent remodeling of the 5′ mRNA cap-binding complex and regulation of small ribosomal subunit scanning during synaptic modification.
Methods
Our methodological strategy is designed to link activity‑dependent molecular events to synapse‑ and circuit‑level plasticity in intact brain tissue. The Bramham lab integrates complementary approaches across molecular, cellular, and systems neuroscience to dissect ARC‑dependent synaptic plasticity. These include:
- In vivo electrophysiology in rodents, combined with genetic, viral, and pharmacological manipulations, to uncover molecular mechanisms of plasticity in defined circuits, cell types and synapses
- Biochemical and proteomic analyses of native protein–protein interactions and post‑translational modifications
- Advanced imaging approaches, including single‑molecule localization microscopy and particle tracking in neuronal cultures, as well as two‑photon and FRET imaging in hippocampal tissue slices
- Nanobody‑based tools for imaging and functional modulation of endogenous proteins
- Recombinant protein expression and purification for biophysical and structural studies
Funding
Top Research (Toppforsk) grant from the Research Council of Norway on the Arc protein. In collaboration with Prof. Jan Haavik, Prof. Petri Kursula, and Prof Aurora Martinez in the Department of Biomedicine, UiB.
EU H2020 Joint Programme in Neurodegenerative Disorders. “Synaptic circuit protection in Alzheimers’s disease (AD) and Huntingtion’s disease (HD): BDNF/TrkB and Arc signaling as rescue factors”. Homepage: CircProt (external link)
Live two-photon excitation imaging of dentate granule cells transduced with fluorescent protein (YPet2) by single-cell electroporation in organotypic rat hippocampal slice-cultures.
Relevant links
CircProt Consortium - Joint Program in Neurodegenerative Disorders (external link)
Center for Neuropsychiatric Disorders
Norwegian Research School in Neuroscience (external link)
International Graduate School in Integrated Neuroscience (IGSIN)