Cross-modal plasticity after partial vision loss in adulthood

: The impact of social isolation, serotonin and the synaptic vesicle cycle

Abstract

The human brain is by far the most remarkable organ in the body. It consists of complex neuronal networks connecting many different cortical and subcortical brain regions, and functions as a control center of the body. It ensures the maintenance of basic physiology by regulating the breathing pattern, heart rate and blood pressure, and it allows an organism to interpret its environment by using its senses and to respond accordingly, for instance by activating motor functions in response to painful stimuli or by releasing neuro-peptides and - hormones to trigger a fight-or-flight response. Brain dysfunction due to epilepsy, stroke, traumatic brain injury, or in the context of neurological diseases, Alzheimer’s Disease or Parkinson’s Disease, strongly correlate with severe changes in the structure and function of the brain. The social brain, in which neuronal circuits underlie perception and comprehension of social features and traits of others such as intentions, drives and emotions, is shaped by neurobiological, environmental and sociocultural factors [1]. Especially the latter makes the social brain extremely vulnerable to the effects of a lack of social interactions, with social deprivation, social isolation (SI) and even worse, perceived loneliness being a problem more and more observed in the increasing population of elderly. Depression, anxiety or panic disorders do therefore not only develop during adolescence when the social brain is still developing, but certainly also during adulthood. Unfortunately, for many types of neurological disorders, medical treatments have not yet been discovered or cannot guarantee the patient’s full recovery [2–4]. Basic research to unravel the fundamental principles of neuroscience, as described in this thesis, can therefore set the stage for future therapies yielding a higher therapeutic efficiency and increased recovery rate as well as a decrease in the number of adverse side-effects related to current therapies.
In this thesis, fundamental neuroscientific questions concerning the cortical response to partial vision loss were posed. The first goal of this PhD dissertation was to better understand the necessity for social interaction during the development of a cross-modal response in order to recover from sensory loss, and to explore the role of monoaminergic neuromodulators therein, with an emphasis on serotonin (5-HT). For this purpose, the adult monocular enucleation (ME) model was investigated under social and SI conditions, since it allowed studying both uni- and cross-modal plasticity phenomena in parallel in mouse sensory cortex.
Second, we sought for molecules and molecular pathways specifically underlying cross-modal plasticity by interrogating potential changes in cell surface protein expression patterns. We focused on neuromodulator (G-protein coupled) receptors (GPCRs), ion channels and transporters displayed at the plasma membrane since these molecules mediate important brain functions and brain plasticity in particular.

Date of Award	29 Apr 2019
Original language	English
Awarding Institution	KU Leuven
Supervisor	Ann Massie (Jury)