An ontologically consistent MRI-based atlas of the mouse diencephalon

In topological terms, the diencephalon lies between the hypothalamus and the midbrain. It is made up of three segments, prosomere 1 (pretectum), prosomere 2 (thalamus), and prosomere 3 (the prethalamus). A number of MRI-based atlases of different parts of the mouse brain have already been published, but none of them displays the segments the diencephalon and their component nuclei. In this study we present a new volumetric atlas identifying 89 structures in the diencephalon of the male C57BL/6J 12 week mouse. This atlas is based on an average of MR scans of 18 mouse brains imaged with a 16.4T scanner. This atlas is available for download at www.imaging.org.au/AMBMC. Additionally, we have created an FSL package to enable nonlinear registration of novel data sets to the AMBMC model and subsequent automatic segmentation

DETECTING BRAIN-WIDE INTRINSIC CONNECTIVITY NETWORKS USING fMRI IN MICE

Functional neuroimaging methods in mice are essential for unraveling complex neuronal networks that underlie maladaptive behavior in neurological disorder models. By using fMRI to detect intrinsic connectivity networks in mice, we can examine large scale alteration in brain activity and functional connectivity to establish causal associations in brain network changes. The work presented in this dissertation is organized into five chapters. Chapter 1 provides the necessary background required to understand how functional neuroimaging tools such as fMRI detect signal changes attributed to spontaneous neuronal activity of intrinsic connectivity networks in mice. Chapter 2 describes the development of our isotropic fMRI acquisition sequence in mice and semi-automated pipeline for mouse fMRI data. Naïve mouse fMRI scans were used to validated the pipeline by reliably and reproducibly extracting intrinsic connectivity networks. Chapter 3 establishes the development and validation of a novel superparamagenetic iron-oxide nanoparticle to enhance fMRI signal sensitivity. Chapter 4 studies the effects norepinephrine released by locus coeruleus neurons on the default mode network in mice. Norepinephrine release selectively enhanced neuronal activity and connectivity in the Frontal module of the default mode network by suppressing information flow from the Retrosplenial-Hippocampal to the Association modules. Chapter 5 addresses the implications of our findings and addresses the limitations and future studies that can be conducted to expand on this research.Doctor of Philosoph