Structural plasticity of synaptic connectivity in the adult hippocampal mossy fiber projection

Abstract

The brain has the lifelong ability to change itself based on new experiences such as learning and memory. This so called neuronal plasticity is reflected in the brain by structural and functional modifications which underlie our ability to learn, remember and adapt our behavior. The present thesis focuses on how learning reshapes structural connectivity between identified elements of neuronal circuits and what is functional role of structural changes in synaptic connectivity in learning and memory? To address these questions, I investigated the relation between structural changes and learning and memory in the hippocampus, a brain region that plays a crucial role in our ability to recall everyday facts and events. I studied the synaptic connectivity of hippocampal mossy fibers upon defined learning events such as spatial navigation in a maze and contextual memory formation upon fear conditioning. In addition, I addressed the behavioral function of these learning-related structural changes at this synaptic site in relation to defined aspects of learning and memory. This study revealed growth of filopodial synapses, specific structural elements of the feedforward inhibitory connectivity at hippocampal mossy fiber terminals upon learning. Furthermore, this study provides causal evidence that learning-related growth of filopodial synapses plays a critical role for the precision of memories but not for associative memory per se. In addition, I also identified spatial and temporal rules for this learning-related plasticity in the different domains along the dorso-ventral axis of the hippocampus and during different forms of learning. In summary, the present thesis provides causal evidence for a selective contribution of presynaptic structural plasticity in defined aspects of learning-related processes. Moreover this study establishes that learning of specific subtasks in complex trial-and-error learning is orchestrated by distinct regional domains along the dorso-ventral axis of the hippocampus. Together, these findings shed a new light on the role of structural plasticity in learning and memory and add to our understanding of the mechanisms underlying learning disabilities and memory impairments.