Trends in Neurosciences
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NMNATs, evolutionarily conserved neuronal maintenance factors.
We review evidence that NMNATs protect neurons through multiple mechanisms in different contexts, and highlight functions that either require or are independent of NMNAT catalytic activity. We then summarize data supporting a role for NMNATs in neuronal maintenance and raise intriguing questions on...
Resting brains never rest: computational insights into potential cognitive architectures.
Resting-state networks (RSNs), which have become a main focus in neuroimaging research, can be best simulated by large-scale cortical models in which networks teeter on the edge of instability. In this state, the functional networks are in a low firing stable state while they are continuously pulled...
Harnessing plasticity to understand learning and treat disease.
I discuss a new perspective on neural plasticity and suggest how plasticity might be targeted to reset dysfunctional circuits. Specifically, a new model is proposed in which map expansion provides a form of replication with variation that supports a Darwinian mechanism to select the most behaviorall...
TNFα in synaptic function: switching gears.
We discuss the evidence in support of synaptic regulation by TNFα and the underlying cellular mechanisms, including control of AMPA receptor trafficking and glutamate release from astrocytes. These findings suggest that increases in TNFα levels (caused by nervous system infection, injury, or disease...
Chemokine CXCL12 in neurodegenerative diseases: an SOS signal for stem cell-based repair.
The dynamic relation between stem cells and their niche governs self-renewal and progenitor cell deployment. The chemokine CXCL12 (C-X-C motif ligand 12) and its signaling receptor CXCR4 (C-X-C motif receptor 4) represent an important pathway that regulates homing and maintenance of stem cells in ne...
Migraine: a disorder of brain excitatory-inhibitory balance?
We review here our current understanding of these mechanisms, focusing on recent advances regarding migraine genetics, headache mechanisms, and the primary brain dysfunction(s) underlying migraine onset and susceptibility to cortical spreading depression, the neurophysiological correlate of migraine...
Seeing the light: photobehavior in fruit fly larvae.
Understanding how sensory stimuli drive behavior requires a detailed understanding of the molecular and neural nature through which the stimuli are received and processed. The visual system of the fruit fly Drosophila melanogaster shares marked similarities to that of mammals. Although much focus ha...
Genetic and cognitive windows into circuit mechanisms of psychiatric disease
We advocate a more systematic approach in characterizing a small number of animal models by utilizing unequivocal rare disease mutations and targeted cognitive assessment to identify convergent disease circuits and mechanisms. Based on available data, we discuss the possibility that the temporal dyn...
TiNSSpecial Issue: Neuropsychiatric Disorders
Balancing act: deubiquitinating enzymes in the nervous system.
Many pathways important to the nervous system are regulated by the post-translational conjugation of ubiquitin to target proteins. The reversal of ubiquitination, or deubiquitination, is equally critical to neuronal function. By countering protein ubiquitination, deubiquitinating enzymes (DUBs) help...