All Publications


  • Identification of discrete, intermingled hypocretin neuronal populations JOURNAL OF COMPARATIVE NEUROLOGY Iyer, M., Essner, R. A., Klingenberg, B., Carter, M. E. 2018; 526 (18): 2937–54

    Abstract

    Neurons in the lateral hypothalamic area that express hypocretin (Hcrt) neuropeptides help regulate many behaviors including wakefulness and reward seeking. These neurons project throughout the brain, including to neural populations that regulate wakefulness, such as the locus coeruleus (LC) and tuberomammilary nucleus (TMN), as well as to populations that regulate reward, such as the nucleus accumbens (NAc) and ventral tegmental area (VTA). To address the roles of Hcrt neurons in seemingly disparate behaviors, it has been proposed that Hcrt neurons can be anatomically subdivided into at least two distinct subpopulations: a "medial group" that projects to the LC and TMN, and a "lateral group" that projects to the NAc and VTA. Here, we use a dual retrograde tracer strategy to test the hypotheses that Hcrt neurons can be classified based on their downstream projections and medial/lateral location within the hypothalamus. We found that individual Hcrt neurons were significantly more likely to project to both the LC and TMN or to both the VTA and NAc than would be predicted by chance. In contrast, we found that Hcrt neurons that projected to the LC or TMN were mostly distinct from Hcrt neurons that projected to the VTA or NAc. Interestingly, these two populations of Hcrt neurons are intermingled within the hypothalamus and cannot be classified into medial or lateral groups. These results suggest that Hcrt neurons can be distinguished based on their downstream projections but are intermingled within the hypothalamus.

    View details for DOI 10.1002/cne.24490

    View details for Web of Science ID 000452567100002

    View details for PubMedID 30019757

    View details for PubMedCentralID PMC6283691

  • Tet2 Rescues Age-Related Regenerative Decline and Enhances Cognitive Function in the Adult Mouse Brain CELL REPORTS Gontier, G., Iyer, M., Shea, J. M., Bieri, G., Wheatley, E. G., Ramalho-Santos, M., Villeda, S. A. 2018; 22 (8): 1974–81

    Abstract

    Restoring adult stem cell function provides an exciting approach for rejuvenating the aging brain. However, molecular mechanisms mediating neurogenic rejuvenation remain elusive. Here we report that the enzyme ten eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes the production of 5-hydroxymethylcytosine (5hmC), rescues age-related decline in adult neurogenesis and enhances cognition in mice. We detected a decrease in Tet2 expression and 5hmC levels in the aged hippocampus associated with adult neurogenesis. Mimicking an aged condition in young adults by abrogating Tet2 expression within the hippocampal neurogenic niche, or adult neural stem cells, decreased neurogenesis and impaired learning and memory. In a heterochronic parabiosis rejuvenation model, hippocampal Tet2 expression was restored. Overexpressing Tet2 in the hippocampal neurogenic niche of mature adults increased 5hmC associated with neurogenic processes, offset the precipitous age-related decline in neurogenesis, and enhanced learning and memory. Our data identify Tet2 as a key molecular mediator of neurogenic rejuvenation.

    View details for DOI 10.1016/j.celrep.2018.02.001

    View details for Web of Science ID 000425489700004

    View details for PubMedID 29466726

    View details for PubMedCentralID PMC5870899

  • Gpr126 Is Critical for Schwann Cell Function during Peripheral Nerve Regeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience Fernandez, C. n., Iyer, M. n., Low, I. n. 2017; 37 (12): 3106–8

    View details for PubMedID 28330980