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Pathological events are well characterized in amyotrophic lateral sclerosis (ALS) mouse models, but review of the literature fails to identify a specific initiating event that precipitates disease pathology. There is now growing consensus in the field that axon and synapses are first cellular sites of degeneration, but controversy exists over whether axon and synapse loss is initiated autonomously at those sites or by pathology in the cell body, in nonneuronal cells or even in nonmotoneurons (MNs). Previous studies have identified pathological events in the mutant superoxide dismutase 1 (SOD1) models involving spinal cord, peripheral axons, neuromuscular junctions (NMJs), or muscle; however, few studies have systematically examined pathogenesis at multiple sites in the same study. We have performed ultrastructural examination of both central and peripheral components of the neuromuscular system in the SOD1G93A mouse model of ALS. Twenty percent of MNs undergo degeneration by P60, but NMJ innervation in fast fatigable muscles is reduced by 40% by P30. Gait alterations and muscle weakness were also found at P30. There was no change in axonal transport prior to initial NMJ denervation. Mitochondrial morphological changes are observed at P7 and become more prominent with disease progression. At P30 there was a significant decrease in excitatory axo-dendritic and axo-somatic synapses with an increase in C-type axo-somatic synapses. Our study examined early pathology in both peripheral and central neuromuscular system. The muscle denervation is associated with functional motor deficits and begins during the first postnatal month in SOD1G93A mice. Physiological dysfunction and pathology in the mitochondria of synapses and MN soma and dendrites occur, and disease onset in these animals begins more than 2 months earlier than originally thought. This information may be valuable for designing preclinical trials that are more likely to impact disease onset and progression.

Abstract-Recent advances in the characterization of small body surfaces with stereophotoclinometry are discussed. The principal data output is an ensemble of landmark maps (L-maps), high-resolution topography/albedo maps of varying resolution that tile the surface of the body. Because they can have a resolution comparable to the best images, and can be located on a global reference frame to high accuracy, L-maps provide a significant improvement in discriminatory power for studies of small bodies, ranging from regolith processes to interior structure. These techniques are now being used to map larger bodies such as the Moon and Mercury. L-maps are combined to produce a standard global topography model (GTM) with about 1.57 million vectors and having a wide variety of applications. They can also be combined to produce high-resolution topography maps that describe local areas with much greater detail than the GTM. When combined with nominal predictions from other data sources and available data from other instruments such as LIDAR or RADAR, solutions for the spacecraft position and camera pointing are the most accurate available. Examples are drawn from studies of Phobos, Eros, and Itokawa, including surface characterization, gravity analysis, spacecraft navigation, and incorporation of LIDAR or RADAR data. This work has important implications for potential future missions such as Deep Interior and the level of navigation and science that can be achieved.