Optical imaging of intrinsic signals during ocular dominance plasticity in a conditional aggrecan knockout mice
Year: 2015
Type: dissertation
Abstract: The nervous system has large capacity to change based on experience and adapt to changes in the environment.However, the level of plasticity is not constant, varying between brain regions and during the development of the animal.These changes imply the existence of mechanisms regulating the level of neuronal plasticity.Recent studies have pointed towards extracellular matrix structures called the perineuronal nets (PNNs) to be important.Experimental disintegration of the PNNs has been shown to increase plasticity in the central nervous system.However, PNNs consist of complex proteoglycan molecules and the functional role of the different components remains unclear.The lectican called aggrecan is a large proteoglycan that has been suggested to have an important role for functional PNNs.However, aggrecan is a critical component of cartilage, and mice deficit in aggrecan will die at birth.This has made it impossible to carry out in-vivo studies in constitutive aggrecan knockout animals.For this study, I had access to a novel conditional aggrecan knockout mouse, allowing aggrecan to be knocked out selectively in local areas in the central nervous system, using the Cre-lox system.This allowed me to do a functional study on plasticity in the visual cortex of aggrecan knockout mice, the first of its kind.Ocular dominance (OD) plasticity is a classic manipulation for studies of activity-dependent plasticity where one eye is closed for several days (monocular deprivation).To assess the effect on OD plasticity I decided to use optical imaging of intrinsic signals, which provides a measure of neuronal activity in a whole brain area based on the hemodynamic response.The first part of my study consisted of setting up this method.Then, I proceeded to knock out aggrecan in the primary visual cortex (V1) of adult mice.The knockout was done by injecting Cre expressing adeno-associated virus in V1, which stopped the expression of aggrecan in this area.Following the injection, a monocular deprivation protocol was employed to assess the level of plasticity.Histology was used to confirm viral transduction, and it revealed a strong reduction of PNN expression in V1.The plasticity assessments point towards an increased level of OD plasticity in the adult aggrecan knockouts, to a level that is similar to the high levels seen in juvenile animals.These results strengthen the hypothesis that aggrecan is essential for the PNNs in regulating the level of neuronal plasticity, at least in primary visual cortex.
Author: Rune Alexander Lanton
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2403521734