Molecular Dynamics of the Synapse (DynamicSyn)

We study the dynamic composition of synapses, the molecular basis of memory encoding in the brain. My lab uses omics-approaches combined with FACs-based synapse purification, metabolic labelling, super-resolution, and live-imaging as well as computational modelling to elucidate changes in synapse composition associated with learning, aging and diseases. We aim for a better understanding of synaptic to help the development of innovative preventive and therapeutic approaches to brain dysfunction.  In 2022, I received an ERC Starting Grant from the European Research Council for my project MemCode, to investigate the mechanisms of long-term memory storage in the brain; and in 2026 an ERC Proof of Concept to test a gene therapy to stop Alzheimer’s disease progression at early stages.

Research topics

Etiology of memory

Many memories acquired during infancy are lost in adulthood, this phenomenon is called childhood amnesia. The ability to retain episodic memories develops only after 3 years in humans and after 17 days in mice. It remains unclear what processes turn on the ability of the brain to store memories for years. High degrees of synaptic plasticity and neurogenesis observed in early childhood may destabilize infant memories. Increasing the stability of memory-encoding synapses between neurons might eventually enable the long-term retention of memories. The protein composition of synapses ultimately determines their strength and stability. Therefore, we hypothesize that alterations in the synaptic proteome during development mediate the ontogeny of memory. To acquire a holistic understanding of the emergence of time-resistant episodic memory in animals, we want to characterize the proteome and transcriptome of synapses during and after the infantile amnesia period.

Elucidating molecular memory traces

At the cellular and network levels it is unclear how memories are retained over long periods of time. The “synaptic trace theory of memory” describes that as information flows through neural networks in the brain, the activity of neurons modifies the protein composition of individual synaptic connections such that previous activity patterns are somewhat retained inside the circuit. These activity-induced changes in the pattern of synaptic connections, a combination of structural and functional plasticity mechanisms, are believed to underlie the long-term storage of information. According to this theory, the stability of memory is directly linked to the stability of synaptic connections recruited during the initial experience. But this theory has been recently challenged by accumulating evidence of the highly dynamic nature of synapses. I propose that presynaptic remodeling induced by synaptic plasticity creates stable presynaptic structures in a local protein synthesis dependent fashion. These stable boutons are attractors of newly formed spines such that long-lasting boutons remain connected to postsynaptic target-neuron through long periods. We use a combination of live- and super-resolution imaging techniques to investigate presynaptic function and plasticity.

Molecular mechanisms of synaptopathies 

Synaptopathies are neurological disorders rooted in dysfunctions at synapses. A central molecular mechanism implicated in many synaptopathies is the disruption of the excitatory (glutamatergic) to inhibitory (GABAergic) transmission balance (E/I balance). This imbalance can lead to hyperexcitability or hypoactivity within neural circuits, contributing to cognitive deficits, seizures, or behavioral abnormalities observed in disorders like autism spectrum disorder (ASD), schizophrenia, epilepsy and in Alzheimer’s disease (AD).