Updated December 1, 2020
Research Spotlight
Sleep disturbance has been implicated as a risk factor for relapse to drug use in humans. However, there have been few direct tests of sleep disturbance on drug seeking behavior. Here, Bjorness & Greene show that only 4 hours of sleep deprivation can enhance the rewarding properties of cocaine and induce mice to selectively seek out the environment where they previously experienced cocaine. Furthermore, antagonism of the orexin system, a system involved in motivation and arousal, reduces this sleep loss-induced seeking of cocaine. These results suggest that even a mild loss of sleep can drive drug seeking behavior via the orexin system, implicating a potential therapeutic role for a pharmaceutical approach that interferes with this sleep loss-sensitive orexin system.
One of the more striking features about microglia that facilitates their responses in the physiological and pathological brain is their remarkable attraction to ATP, sensed by the P2Y12 receptor. However, the intracellular signaling mediating this directed motility is largely unknown. Whitelaw et al. show that phosphoinositide-3-kinase (PI3K) activity is required for ATP-mediated microglial motility. However, PI3K𝛾, the isoform directly activated by G-protein coupled receptors, plays only a subtle modulatory role. Thus, P2Y12 likely activates PI3K indirectly to promote microglial motility. Understanding this signaling pathway could be important for specific targeting of microglial responses.
Pannexin 1 Regulates Dendritic Protrusion Dynamics in Immature Cortical Neurons
Developing neurons build tiny, highly dynamic ‘dendritic protrusions’ that mature and stabilize into specialized structures called dendritic spines in order to receive information from other neurons. Sanchez-Arias et al. found that a channel-forming protein called pannexin 1 (PANX1) regulates the density of the dendritic spines in cortical neurons. To better understand how PANX1 regulates dendritic spine density, the authors created new methods to measure the movement of dendritic protrusions and changed the amount of PANX1 in the neurons to see if that had an effect. Ultimately, the authors found that the levels of PANX1 correlated with dendritic spine movement – in other words, less movement was associated with less PANX1; while more movement was associated with more PANX1. This work advances our understanding of the impact of PANX1 on neuronal development and provides additional tools to the neuroscience research community to study dendritic protrusion dynamics.
Atypical cadherin FAT3 is a novel mediator for morphological changes of microglia
Microglia play an important role in the formation of neural circuits during the postnatal stage. Microglia usually contribute to regulating synaptogenesis and synapse pruning by stretching and contracting their processes. However, the mechanism of morphological changes in microglia is not well understood. Okajima et al. show that the atypical cadherin family protein FAT3 is a novel factor that stabilizes microglial processes. This finding may be related to neurodevelopmental disorders.
Stay updated on the latest research: Sign up and manage your Alerts to receive emails of table of contents, searching, and article citation alerts for both issues and Early Release articles.