Objective Notch signaling has been identified as a critical regulator in cartilage development and joint maintenance, and loss of Notch signaling in all joint tissues results in an early and progressive osteoarthritis (OA)-like pathology. This study investigated the targeted cell population within the knee joint in which Notch signaling is required for normal cartilage and joint integrity. Methods Two loss-of-function mouse models were generated with tissue-specific knockout of the core Notch signaling component, RBPjκ. The AcanCreERT2 transgene specifically removed Rbpjκ floxed alleles in postnatal joint chondrocytes, while the Col1Cre(2.3kb) transgene deleted Rbpjκ in osteoblast populations, including subchondral osteoblasts. Mutant and control mice were analyzed via histology, immunohistochemistry, real-time qPCR, X-ray, and microCT imaging at multiple time-points. Results Loss of Notch signaling in postnatal joint chondrocytes results in a progressive OA-like pathology, and triggered the recruitment of non-targeted fibrotic cells into the articular cartilage potentially due to mis-regulated chemokine expression from within the cartilage. Upon recruitment, these fibrotic cells produced degenerative enzymes that may lead to the observed cartilage degradation and contribute to a significant portion of the age-related OA-like pathology. On the contrary, loss of Notch signaling in subchondral osteoblasts did not affect normal cartilage development or joint maintenance. Conclusions RBPjκ-dependent Notch signaling in postnatal joint chondrocytes, but not subchondral osteoblasts, is required for articular cartilage and joint maintenance.

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Kubanek J, Wang C, Snyder LH. Neuronal responses to target onset in oculomotor and somatomotor parietal circuits differ markedly in a choice task. J Neurophysiol 110: 2247-2256, 2013. First published August 21, 2013 doi:10.1152/jn.00968.2012We often look at and sometimes reach for visible targets. Looking at a target is fast and relatively easy. By comparison, reaching for an object is slower and is associated with a larger cost. We hypothesized that, as a result of these differences, abrupt visual onsets may drive the circuits involved in saccade planning more directly and with less intermediate regulation than the circuits involved in reach planning. To test this hypothesis, we recorded discharge activity of neurons in the parietal oculomotor system (area LIP) and in the parietal somatomotor system (area PRR) while monkeys performed a visually guided movement task and a choice task. We found that in the visually guided movement task LIP neurons show a prominent transient response to target onset. PRR neurons also show a transient response, although this response is reduced in amplitude, is delayed, and has a slower rise time compared with LIP. A more striking difference is observed in the choice task. The transient response of PRR neurons is almost completely abolished and replaced with a slow buildup of activity, while the LIP response is merely delayed and reduced in amplitude. Our findings suggest that the oculomotor system is more closely and obligatorily coupled to the visual system, whereas the somatomotor system operates in a more discriminating manner.LIP; decision; parietal reach region; reward; transient BEHAVIOR IS OFTEN GUIDED OR influenced by objects appearing on the visual scene. The appearance or movement of an object often elicits a rapid eye movement, or saccade, to that object. The benefit of this behavior is to bring the object onto the fovea to acquire more detailed visual information about it. Saccades can be deployed quickly and therefore are relatively inexpensive. In comparison, the appearance or movement of an object rarely elicits an immediate reach, although a subject may choose to reach after a delay. Reaching is slower and requires a greater commitment of resources and more involved planning, including the trajectory to follow and what the hand will do when it arrives. In general, we are much more likely to immediately look at a new visual target than we are to immediately reach for it.Targets of visually guided saccades and reaches are encoded by many neurons in posterior parietal cortex. Specifically, neurons in the lateral intraparietal area (LIP) and the parietal reach region (PRR) respond to the appearance of a taskrelevant visual target in their response field (RF) with a transient increase in activity (Goldberg and Bruce 1985;Blatt et al. 1990;Colby et al. 1996;Gottlieb et al. 1998;Colby and Goldberg 1999;Snyder et al. 1997Snyder et al. , 2000Calton et al. 2002;Scherberger and Andersen 2007; Andersen 2007, 2011;Pesaran et al. 2008). The parietal regions LIP and PRR might th...

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