01/06/2021 to 31/05/2023

PI: Joana Ferreira

The aim of the “A New Trans-Synaptic Bridge: Functional characterization of the NMDA receptor-Neurexin-2 interaction” project was to confirm the hypothesis that NMDA receptors (NMDARs) were able to directly interact with Neurexins (Nrxn).   Together, our experiments revealed dynamic changes in the distribution and interplay of different Nrxn isoforms with NMDAR containing the GluN2B or the GluN2A subunit during developmental stages. 

15/01/2022 to 14/01/2024

PI: Joana Ferreira

We are studying the interaction between two major synaptic players, the GluN2B subunit of N-methyl-D-aspartate type receptors (NMDARs) and the presynaptic molecule Neurexin2. Given their crucial role in brain development and synaptic plasticity, this interaction is thought to have a major impact in neurotransmission. Both proteins have been highly associated with neuropsychiatric disorders including schizophrenia. The molecular complex GluN2B-Neurexin2 will be thoroughly investigated in this project using a combination of biochemical, confocal, and state-of-the-art super-resolution imaging and electrophysiology techniques. Consequences of interfering with this interaction for synaptic physiology and animal behavior will be comprehensively examined.

Reference: FCT_2022.05386.PTDC

01/03/2023 to 31/08/2024

PI: Joana Ferreira; Co-PI: Sílvia Viana da Silva (DNZE, Berlin)

We propose to explore how the interaction GluN2B-NMDARs-Nrxn2 is crucial for synaptic localization and transsynaptic alignment of these proteins and develop the tools to evaluate the impact of this complex for brain physiology. This project will shed a new light on the interaction between Nrxns and NMDARs and their reciprocal regulation and impact on synapse organization. We believe the fine regulation of the nanoscale architecture of the complex NMDARs-Nrxn profoundly impacts the efficiency of synaptic transmission. We will develop the tools that will allow us to evaluate the consequences of interfering with this interaction or altering their nanoscale organization on synaptic physiology and animal behavior. Its outcome will be crucial for our understanding of transsynaptic signaling mechanisms in physiological and pathological conditions. The ability to precisely define the processes that control NMDAR localization and function will be fundamental for the development of new therapeutics to ameliorate NMDAR related dysfunction, and related pathologies like SCZ.

Reference: LCF/PR/HP20/52300003

01/12/2020 to 30/11/2024

PI: Ana Luísa Carvalho; Co-PI: Joana Ferreira

The project "Potassium channel dysfunction in models of neurodevelopmental disorders" addresses the regulation of M-currents by stargazin, and its impairment in human neurons and knock-in mice expressing stargazin variants associated with neurodevelopmental disorders.

Defects of homeostatic plasticity in autism: contributions of the study of human mutations of the gene CNTNAP2

• Dr. Xavier Altafaj Tardio
  Facultat de Medicina i Ciències de la Salut - Universitat de Barcelona

• Dra. Ana Luisa Monteiro de Carvalho
  Centro de Neurociências e Biologia Celular - Universidade de Coimbra Portugal