Lectures and seminars From proteins to circuits: defining pyramidal neuron input architecture and remodeling in disease

Speaker:

Joris De Wit, VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium.

Time: 7 May, 11:00–12:00

Location: Ragnar Granit Lecture Hall, Biomedicum (level 3)

Title: From proteins to circuits: defining pyramidal neuron input architecture and remodeling in disease

Abstract

Neural circuits are composed of different types of neurons and the specific patterns of synaptic connectivity between them. The highly heterogeneous nature of neuronal cell types and their connections present a major challenge to the characterization of neural circuits at the molecular level. Progress in addressing this challenge has come from transcriptomic profiling techniques, which enabled the characterization of the molecular composition of specific cell types within circuits. While single-cell transcriptomics have been instrumental in mapping cell-type diversity in the brain, these approaches are poorly suited to capture the diversity and molecular identity of synapses. In this talk, I will present our recent efforts to map synapse composition and diversity in neural circuits, using fluorescent sorting of synaptosomes and synaptic proximity biotinylation approaches coupled with mass spectrometry. We analyze the postsynaptic proteome of CA1 hippocampal pyramidal neurons and characterize the specific molecular composition of their proximal and distal inputs. As CA1 pyramidal neurons are especially vulnerable in Alzheimer’s disease (AD), we use these approaches to map their postsynaptic protein composition in App^NL-G-F mice and detect early and progressive synaptic changes in AD. These proteomics approaches enable the dissection of synapse composition in intact neural circuits in health and disease, and should be broadly applicable to other brain regions and neuron types.

Recent publications

Synaptic signatures and disease vulnerabilities of layer 5 pyramidal neurons.
Marcassa G, Dascenco D, Lorente-Echeverría B, Daaboul D, Vandensteen J, Leysen E, Baltussen L, Howden AJM, de Wit J
Nat Commun 2025 Jan;16(1):228

A postsynaptic GPR158-PLCXD2 complex controls spine apparatus abundance and dendritic spine maturation.
Verpoort B, Amado L, Vandensteen J, Leysen E, Dascenco D, Vandenbempt J, Lemmens I, Wauman J, Vennekens K, Escamilla-Ayala A, Freitas ACN, Voets T, Munck S, Tavernier J, Wierda K, de Wit J
Dev Cell 2025 Sep;60(18):2470-2486.e10

A dynamic gene regulatory code drives synaptic development of hippocampal granule cells.
Lorente-Echeverría B, Daaboul D, Vandensteen J, Marcassa G, Naert W, Vandenbempt J, Leysen E, Reverendo M, Vlaeminck I, Vervloessem L, Lamote J, Poovathingal S, Davie K, Wierda K, Dascenco D, Aerts S, de Wit J
Sci Adv 2025 Oct;11(43):eadx5140

Early alterations in the MCH system link aberrant neuronal activity and sleep disturbances in a mouse model of Alzheimer's disease.
Calafate S, Özturan G, Thrupp N, Vanderlinden J, Santa-Marinha L, Morais-Ribeiro R, Ruggiero A, Bozic I, Rusterholz T, Lorente-Echeverría B, Dias M, Chen WT, Fiers M, Lu A, Vlaeminck I, Creemers E, Craessaerts K, Vandenbempt J, van Boekholdt L, Poovathingal S, Davie K, Thal DR, Wierda K, Oliveira TG, Slutsky I, Adamantidis A, De Strooper B, de Wit J
Nat Neurosci 2023 Jun;26(6):1021-1031

LRRC37B is a human modifier of voltage-gated sodium channels and axon excitability in cortical neurons.
Libé-Philippot B, Lejeune A, Wierda K, Louros N, Erkol E, Vlaeminck I, Beckers S, Gaspariunaite V, Bilheu A, Konstantoulea K, Nyitrai H, De Vleeschouwer M, Vennekens KM, Vidal N, Bird TW, Soto DC, Jaspers T, Dewilde M, Dennis MY, Rousseau F, Comoletti D, Schymkowitz J, Theys T, de Wit J, Vanderhaeghen P
Cell 2023 Dec;186(26):5766-5783.e25

Refreshments

Sandwiches and coffee will be provided.

Registration

No registration is needed.