/ Research

Synapse Architecture Group

Group Leader

Joana Ferreira

Research:

Synapse Architecture Group: Understanding Ageing and Cognitive Health

The Synapse Architecture Group investigates the molecular and structural changes in synapses that underlie memory and cognitive performance. Our primary goal is to understand how ageing affects synaptic function and contributes to cognitive decline, associated with ageing, as well as neuropsychiatric and neurodegenerative disorders. Using cutting-edge biochemistry, molecular imaging, and advanced microscopy, we explore how synaptic architecture evolves with aging and how these changes impact neuronal communication.

Key Research Areas

Nanoscale Synapse Organization:

Leveraging super-resolution microscopy, we examine the nanoscale structure of synapses, particularly trans-synaptic connections, to understand how dynamic protein interactions regulate synaptic plasticity.

Aging and Synapse Function:

We study how ageing alters synapse morphology and molecular composition, identifying mechanisms that contribute to cognitive decline or confer resilience.

Synaptic Resilience and Vulnerability:

We investigate what differentiates resilient synapses from those prone to ageing-related deterioration, exploring molecular and structural factors, including potential sex-specific differences.

By investigating the nanoscale architecture of synapses and the intricate molecular interactions that underlie cognitive performance, we aim to uncover key principles of neuronal communication and plasticity, in health and disease. This fundamental knowledge is crucial for building a comprehensive understanding of brain function across the lifespan.

Relevant publications:

Ferreira JS‡, Dupuis JP, Kellermayer B, Bénac N, Manso C, Bouchet D, Levet F, Butler C, Sibarita J-B, and Groc L‡ (2020) Distance-dependent regulation of NMDAR nanoscale organization along hippocampal neuron dendrites. PNAS, Sep 2020, 117 (39) 24526-24533. DOI: 10.1073/pnas.1922477117. ‡ Co-corresponding authors.

Kellermayer B*, Ferreira JS*, Dupuis J*, Levet F, Grillo-Bosch D, Bard L, Linarès-Loyez J, Bouchet D, Choquet D, Rusakov DA, Bon P, Sibarita J, Cognet L, Sainlos M, Carvalho AL and Groc L. (2018) Differential Nanoscale Topography and Functional Role of GluN2-NMDA Receptor Subtypes at Glutamatergic Synapses. Neuron 2018 Oct 10; 100(1):106-119.e7. DOI: 10.1016/j.neuron.2018.09.012. * Equal contribution.

Hosokawa T, Liu PW, Cai Q., Ferreira JS, Levet F, Corey Butler, Jean-Baptiste Sibarita, Daniel Choquet, Laurent Groc, Eric Hosy, Mingjie Zhang & Yasunori Hayashi. (2021) CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation. Nature Neuroscience 24, 777–785. DOI: 10.1038/s41593-021-00843-3

Ferreira JS*, Papouin T*, Ladépêche L, Yao A, Langlais VC, Bouchet D, Dulong J, Mothet J, Sacchi S, Pollegioni L, Paoletti P, Oliet SHR and Groc L. (2017) Co-agonists differentially tune GluN2B-NMDA receptor trafficking at hippocampal synapses. eLife 2017;6:e25492. DOI: 10.7554/eLife.25492. * Equal contribution.

Ferreira JS, Schmidt J, Rio P, Águas R, Rooyakkers A, Li KW, Smit AB, Craig AM, Carvalho AL. (2015) GluN2B-Containing NMDA Receptors Regulate AMPA Receptor Traffic through Anchoring of the Synaptic Proteasome. Journal of Neuroscience 35 (22): 8462-8479. DOI: 10.1523/JNEUROSCI.3567-14.2015

Ferreira JS, Kellermayer B, Carvalho AL, Groc L (2021) Interplay between NMDA receptor dynamics and the synaptic proteasome. European Journal of Neuroscience 54 (6), 6000 – 6011. DOI: 10.1111/ejn.15427. ‡ Co-corresponding authors.

Paviolo C*, Ferreira JS*, Lee A, Hunter D, Calaresu I, Nandi S, Groc L, Cognet L. (2022) Near-infrared Carbon Nanotube Tracking Reveals the Nanoscale Extracellular Space around Synapses. Nano Letters 2022, 22, 17, 6849–6856. DOI: 10.1021/acs.nanolett.1c04259. * Equal contribution.

Ferreira, JS, Groc, L (2024) Surface Glutamate Receptor Nanoscale Organization with Super-Resolution Microscopy (dSTORM). In: Kukley, M. (eds) New Technologies for Glutamate Interaction. Neuromethods, vol 207. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3742-5_2. ‡ Co-corresponding authors.

Team

Carlos Cação
Laboratory Technician
Diogo Tomé
Assistant Researcher
Giulia Tombesi
Assistant Researcher
João Martins
PhD Student