Schafer D.P.,Fm Kirby Neurobiology Center |
Stevens B.,Harvard University
Biochemical Society Transactions | Year: 2010
Synapse elimination is a normal developmental process occurring throughout the central and peripheral nervous systems. Meanwhile, gradual and early loss of synapses is a characteristic that is common to several neurodegenerative disease states. Recent evidence has emerged implicating molecules canonically involved in the immune system and inflammation accompanying neurodegeneration (e.g. classical complement cascade) as important players in the normal elimination of synapses in the developing nervous system. As a result, a question has emerged as to whether mechanisms underlying elimination of synapses during normal development are recapitulated and contribute to early synapse loss and nervous system dysfunction during neurodegenerative disease. The present review explores this possibility and provides a description of many neuroimmune proteins that may participate in the elimination of synapses and synaptic dysfunction in the developing and diseased brain. ©The Authors.
Hensch T.K.,Harvard University |
Hensch T.K.,Fm Kirby Neurobiology Center
Cell | Year: 2014
Experience shapes brain function throughout life to varying degrees. In a recent issue of Nature, Donato et al. identify reversible shifts in focal parvalbumin cell state during adult learning, placing it on a mechanistic continuum with developmental critical periods. A disinhibitory microcircuit controls the plasticity switch to modulate memory formation. © 2014 Elsevier Inc.
Lehrman E.K.,Fm Kirby Neurobiology Center |
Stevens B.,Fm Kirby Neurobiology Center
Cell | Year: 2015
Cancer is known for opportunistically utilizing resources from its surroundings for its own growth and survival. In this issue of Cell, Venkatesh et al. demonstrate that this also occurs in the brain, identifying neuronal activity-induced secretion of neuroligin-3 as a novel mechanism promoting glioma proliferation. © 2015 Elsevier Inc.
Wan G.,Fm Kirby Neurobiology Center |
Wan G.,Harvard University |
Corfas G.,Fm Kirby Neurobiology Center |
Corfas G.,Harvard University |
Stone J.S.,University of Washington
Seminars in Cell and Developmental Biology | Year: 2013
Sensory epithelia of the inner ear contain two major cell types: hair cells and supporting cells. It has been clear for a long time that hair cells play critical roles in mechanoreception and synaptic transmission. In contrast, until recently the more abundant supporting cells were viewed as serving primarily structural and homeostatic functions. In this review, we discuss the growing information about the roles that supporting cells play in the development, function and maintenance of the inner ear, their activities in pathological states, their potential for hair cell regeneration, and the mechanisms underlying these processes. © 2013 Elsevier Ltd.
Greer P.L.,Harvard University |
Hanayama R.,Harvard University |
Bloodgood B.L.,Harvard University |
Mardinly A.R.,Harvard University |
And 11 more authors.
Cell | Year: 2010
Angelman Syndrome is a debilitating neurological disorder caused by mutation of the E3 ubiquitin ligase Ube3A, a gene whose mutation has also recently been associated with autism spectrum disorders (ASDs). The function of Ube3A during nervous system development and how Ube3A mutations give rise to cognitive impairment in individuals with Angleman Syndrome and ASDs are not clear. We report here that experience-driven neuronal activity induces Ube3A transcription and that Ube3A then regulates excitatory synapse development by controlling the degradation of Arc, a synaptic protein that promotes the internalization of the AMPA subtype of glutamate receptors. We find that disruption of Ube3A function in neurons leads to an increase in Arc expression and a concomitant decrease in the number of AMPA receptors at excitatory synapses. We propose that this deregulation of AMPA receptor expression at synapses may contribute to the cognitive dysfunction that occurs in Angelman Syndrome and possibly other ASDs. © 2010 Elsevier Inc. All rights reserved.