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Identifier

000419741

Title

The role of autophagy in shaping inhibitory synapses

Alternative Title

Ο ρόλος της αυτοφαγίας στη διαμόρφωση ανασταλτικών συνάψεων

Author

Κόλλιας, Αναστάσιος Χ.

Thesis advisor

Νικολετοπούλου, Βασιλική
Σιδηροπούλου, Κυριακή

Abstract

Macroautophagy is a highly conserved multistep process that sequesters cellular constituents in autophagic vesicles and delivers them to the lysosome for degradation. Though initially considered as a process in bulk, it is increasingly appreciated that autophagy can serve specific functions in specialized cell types. In line with this notion, recent evidence suggests that autophagy is modulated by neuronal activity in glutamatergic hippocampal neurons and that its ablation in excitatory neurons results in autistic-like behaviors due to aberrant developmental spine pruning, a process known to be mediated by LTD-like mechanisms. As excitatory neurons represent the vast majority in the forebrain and synaptic plasticity traditionally studied in these cells has been shown to underlie key cognitive functions such as memory and learning, work so far has focused on delineating the role of autophagy in excitatory neurons, ignoring the minority interneuron populations responsible for brain inhibition. We characterized the role of autophagy in shaping inhibitory synapses by generating the first knockout mice with conditional deletion of Atg5, a gene that is required for autophagy, in interneurons derived from the medial ganglionic eminence (MGE). Our findings suggest that autophagy has a crucial role in dictating brain inhibition, as autophagy-deficiency in GABAergic neurons leads to increased inhibition and compromised synaptic plasticity and memory.

Language

English

Subject

Brain inhibition

Synaptic plasticity

Αναστολή εγκεφάλου

Συναπτική πλαστικότητα

Issue date

2018-11-23

Collection

School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses

Type of Work--Post-graduate theses