Regulation der extrazellulären Matrix durch Dopamin während des Lernens im erwachsenen Alter.
Kognitive, systemische und Verhaltensneurobiologie
Zusammenfassung der Projektergebnisse
A specialized form of the extracellular matrix (ECM) emerges during adolescence, stabilizing synaptic networks but limiting plasticity in the adult brain. This project investigated how dynamic ECM regulation—specifically of the proteoglycan brevican— enables plasticity during adult learning, and whether this process depends on neuromodulators like dopamine. Using acute hippocampal slices, we showed that the proteases ADAMTS-4 and -5 mediate activity-dependent cleavage of brevican shortly after synaptic stimulation. Blocking these proteases impaired the formation of new dendritic protrusions, highlighting ECM breakdown as a prerequisite for structural synaptic plasticity. To extend these insights to intact networks, we used in vivo laminar recordings in gerbils combined with ECM degradation. We found a redistribution of synaptic activity from deep to superficial layers and increased lateral integration, suggesting that ECM integrity shapes cortical input processing. Building on this, we developed a new model combining chronic laminar recordings with a reversal learning task. We found that prediction errors activated deep cortical layers—mirroring dopaminergic error signaling—while successful learning shifted activity to superficial layers with increased gamma and beta oscillations. Together, these findings establish that ECM remodeling enables adaptive cortical reorganization during learning. The project thus links molecular ECM plasticity with systems-level circuit dynamics during behavior.
Projektbezogene Publikationen (Auswahl)
-
The extracellular matrix regulates cortical layer dynamics and cross-columnar frequency integration in the auditory cortex. Communications Biology, 4(1).
El-Tabbal, Mohamed; Niekisch, Hartmut; Henschke, Julia U.; Budinger, Eike; Frischknecht, Renato; Deliano, Matthias & Happel, Max F. K.
-
FENS 2022: Cortical circuit dynamics after removal of the Extracellular Matrix
Ebru Acun & Max Happel
-
FENS 2022: Inactivity induced homeostatic synaptic plasticity requires ECM remodelling
Bartomeu Perelló Amorós & Renato Frischknecht
-
Mice deficient in synaptic protease neurotrypsin show impaired spaced long-term potentiation and blunted learning-induced modulation of dendritic spines. Cellular and Molecular Life Sciences, 80(4).
Ferrer-Ferrer, Maura; Jia, Shaobo; Kaushik, Rahul; Schneeberg, Jenny; Figiel, Izabela; Aleshin, Stepan; Mironov, Andrey; Safari, Motahareh; Frischknecht, Renato; Wlodarczyk, Jakub; Senkov, Oleg & Dityatev, Alexander
-
NWG 2023: Inactivity induced homeostatic synaptic plasticity requires ECM remodelling
Bartomeu Perelló Amorós & Renato Frischknecht
-
FENS 2024: ECM Remodeling by ADAMTS5 is Critical for Inactivity-Induced Homeostatic Plasticity Mechanisms
Bartomeu Perelló-Amorós & Renato Frischknecht
-
SfN 2024: Cortical circuit plasticity in an auditory reversal Shuttle-box task in Mongolian gerbils
Ebru Acun & Max Happel
-
Activity-dependent extracellular proteolytic cascade cleaves the ECM component brevican to promote structural plasticity. EMBO Reports, 27(1), 163-185.
Singh, Jeet Bahadur; Perelló-Amorós, Bartomeu; Schneeberg, Jenny; Mirzapourdelavar, Hadi; Seidenbecher, Constanze I.; Fejtová, Anna; Dityatev, Alexander & Frischknecht, Renato
-
Serotonergic Psychedelics Rapidly Modulate Evoked Glutamate Release in Cultured Cortical Neurons. Journal of Neurochemistry, 169(3).
Petrušková, Aneta; Guhathakurta, Debarpan; Akdaş, Enes Yağız; Perelló‐Amorós, Bartomeu; Frischknecht, Renato; Weiss, Eva‐Maria; Páleníček, Tomáš & Fejtová, Anna
