Many forms of long-term synaptic plasticity that underlie key cognitive functions, such as memory formation, memory erasure and behavioral flexibility, require protein turnover, meaning both protein synthesis and degradation. Autophagy is a major pathway for protein degradation, yet its requirement in synaptic plasticity remains unknown. The aim of this project is to characterize the contribution of autophagy in different forms of synaptic plasticity. Similarly, the regulation of autophagosome biogenesis and flux in neurons under conditions of synaptic activation is also elusive and is addressed in our lab. To these ends, we use molecular biology tools, electron microscopy (Figure 1), genetic models, electrophysiology and behavioral analyses.
RESEARCH & TECHNOLOGY
- Requirement of autophagy-mediated protein homeostasis for synaptic plasticity
- Secretory autophagy in neurons
- Nuclear functions of autophagy genes in neurons
- Regulation of neuronal autophagy by neurotrophic factors
Requirement of autophagy-mediated protein homeostasis for synaptic plasticity
Secretory autophagy in neurons
In addition to their classical role in delivering cargo to the lysosome for degradation, autophagic vesicles have recently also been implicated in unconventional protein secretion (Figure 2). While the role of secretory autophagy has been studied in yeast, cell lines, and non-neuronal cells, its presence and function in neurons remains elusive. This project investigates where, how and why secretory autophagy operates in neurons.
Nuclear functions of autophagy genes in neurons
Following our serendipitous observation that certain autophagic proteins are also localized in neuronal nuclei (Figure 3), this project investigates conventional and unconventional nuclear roles of components of the autophagic machinery in neurons.
Regulation of neuronal autophagy by neurotrophic factors
Our recent work demonstrated that Brain derived neurotrophic factor (BDNF), the main neurotrophic factor in the adult brain, suppresses autophagy in neurons (Figure 4). Following up on these findings, we explore the regulation of autophagy in central and peripheral neurons by neurotrophic factors and its relevance to synaptic function and life-death decisions.