TGM6-IgG may be a candidate CSF biomarker to predict and monitor disease activity in progressive MS patients. Furthermore, TGM6 expression by reactive astrocytes within both human and mouse lesions suggests its involvement in the mechanisms of glial scar formation.

Experience governs neurogenesis from radial-glial neural stem cells (RGLs) in the adult hippocampus to support memory. Transcription factors in RGLs integrate physiological signals to dictate self-renewal division mode. Whereas asymmetric RGL divisions drive neurogenesis during favorable conditions, symmetric divisions prevent premature neurogenesis while amplifying RGLs to anticipate future neurogenic demands. The identities of transcription factors regulating RGL symmetric self-renewal, unlike those that regulate RGL asymmetric self-renewal, are not known. Here, we show in mice that the transcription factor Kruppel-like factor 9 (Klf9) is elevated in quiescent RGLs and inducible, deletion of Klf9 promotes RGL activation state. Clonal analysis and longitudinal intravital 2-photon imaging directly demonstrate that Klf9 functions as a brake on RGL symmetric self-renewal. In vivo translational profiling of RGLs lacking Klf9 generated a molecular blueprint for RGL symmetric self-renewal that was characterized by upregulation of genetic programs underlying Notch and mitogen signaling, cell-cycle, fatty acid oxidation and lipogenesis. Together, these observations identify Klf9 as a transcriptional regulator of neural stem cell expansion in the adult hippocampus.

Adult neurogenesis is a unique form of neuronal plasticity in which newly generated neurons are integrated into the adult dentate gyrus in a process that is modulated environmental stimuli. Adult-born neurons can contribute to spatial memory but it is unknown whether they alter neural representations of space in the hippocampus. Using in vivo two-photon calcium imaging, we found that mice that were previously housed in an enriched environment, which triggers an increase in neurogenesis, had increased spatial information encoding in the hippocampal dentate gyrus during novel context exposure. Ablating adult neurogenesis by prior focal irradiation of the hippocampus blocked the effect of enrichment and lowered spatial information content, as did the chemogenetic silencing of adult-born neurons. Both ablating neurogenesis and silencing adult-born neurons decreased the calcium activity rates of dentate gyrus neurons, resulting in a decreased amplitude of place-specific responses. These findings are in contrast to previous studies that suggested a predominantly inhibitory action for adult-born neurons. We propose that adult neurogenesis improves neural representations of space by increasing the gain of dentate gyrus neurons and thereby improving their ability to tune to spatial features. This mechanism may mediate the beneficial effects of environmental enrichment on spatial learning and memory.

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Aging is associated with cognitive deficits, with spatial memory being very susceptible to decline. The hippocampal dentate gyrus (DG) is important for processing spatial information in the brain and is particularly vulnerable to aging, yet its sparse activity has led to difficulties in assessing changes in this area. Using in vivo two‐photon calcium imaging, we compared DG neuronal activity and representations of space in young and aged mice walking on an unfamiliar treadmill. We found that calcium activity was significantly higher and less tuned to location in aged mice, resulting in decreased spatial information encoded in the DG. However, with repeated exposure to the same treadmill, both spatial tuning and information levels in aged mice became similar to young mice, while activity remained elevated. Our results show that spatial representations of novel environments are impaired in the aged hippocampus and gradually improve with increased familiarity. Moreover, while the aged DG is hyperexcitable, this does not disrupt neural representations of familiar environments.

Aging is associated with cognitive deficits, with spatial memory being very susceptible to decline. The hippocampal dentate gyrus (DG) is important for the processing of spatial information in the brain and is particularly vulnerable to aging, yet its sparse activity has led to difficulties in assessing changes in this area. Usingin vivotwo-photon calcium imaging, we compared DG neuronal activity and representations of space in young and aged mice walking on an unfamiliar treadmill. We found that calcium activity was significantly higher and less tuned to location in aged mice, resulting in decreased spatial information encoded in the DG. However, with repeated exposure to the same treadmill, both spatial tuning and information levels in aged mice became similar to young mice, while activity remained elevated. Our results show that spatial representations of novel environments are impaired in the aged hippocampus and gradually improve with increased familiarity. Moreover, while the aged DG is hyperexcitable, this does not disrupt neural representations of familiar environments.