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SUMMARYNeuronal activity during experience is thought to induce plastic changes within the hippocampal network which underlie memory formation, although the extent and details of such changesin vivoremain unclear. Here, we employed a temporally precise marker of neuronal activity, CaMPARI2, to label active CA1 hippocampal neuronsin vivo, followed by immediate acute slice preparation and electrophysiological quantification of synaptic properties. Recently active neurons in the superficial sublayer ofstratum pyramidaledisplayed larger post-synaptic responses at excitatory synapses from area CA3, with no change in pre-synaptic release probability. In contrast,in vivoactivity weakened both pre- and post-synaptic excitatory weights onto pyramidal cells in the deep sublayer.In vivoactivity of deep and superficial neurons within sharp-wave ripples was bidirectionally changed across experience, consistent with the observed changes in synaptic weights. These findings reveal novel, fundamental mechanisms through which the hippocampal network is modified by experience to store information.

The discovery of meningeal lymphatic vessels (LVs) has sparked interest in identifying their role in diseases of the central nervous system. Similar to peripheral LVs, meningeal LVs depend on vascular endothelial growth factor receptor-3 (VEGFR3) signaling for development. Here we characterize the effect of stroke on meningeal LVs, and the impact of meningeal lymphatic hypoplasia on post-stroke outcomes. We show that photothrombosis (PT), but not transient middle cerebral artery occlusion (tMCAo), induces meningeal lymphangiogenesis in young male C57Bl/J6 mice. We also show that Vegfr3wt/mut mice develop significantly fewer meningeal LVs than Vegfr3wt/wt mice. Again, meningeal lymphangiogenesis occurs in the alymphatic zone lateral to the sagittal sinus only after PT-induced stroke in Vegfr3wt/wt mice. Interestingly, Vegfr3wt/mut mice develop larger stroke volumes than Vegfr3wt/wt mice after tMCAo, but not after PT. Our results reveal differences between PT and tMCAo models of stroke and underscore the need to consider method of stroke induction when investigating the role of meningeal lymphatics. Taken together, our data indicate that ischemic injury can induce the growth of meningeal LVs and that the absence of these LVs can impact post-stroke outcomes.

Astrocytes play a critical role in supporting the normal physiological function of neurons. Recent studies have revealed that astrocyte transplantation can promote axonal regeneration and functional recovery after spinal cord injury. Biomaterial can be designed as a growth-permissive substrate and serve as a carrier for astrocyte transplantation into injured spinal cord. In this study, we developed a method to generate collagen microspheres encapsulating astrocytes by injecting a mixture of collagen and astrocytes into a cell culture medium with a syringe controlled by a syringe pump. The collagen microspheres were crosslinked with poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-StarPEG) to reduce the degradation rate. The viability of cells in the crosslinked microspheres was higher than 90%. Astrocytes were transfected with plasmids encoding nerve growth factor (NGF)-ires-enhanced green fluorescent protein (EGFP) genes by electroporation and encapsulated in crosslinked microspheres. The level of NGF released into the cell culture medium was higher than that remaining in the microspheres or astrocytes. When microspheres encapsulating astrocytes transfected with plasmids encoding NGF-ires-EGFP genes were added into the cultured rat dorsal root ganglion, the axonal growth was significantly enhanced. This study shows that the microspheres can be potentially used as a carrier of astrocytes to promote nerve regeneration in injured neural tissue.

Attentional capture is a phenomenon in which rewarded stimuli become more salient, automatically drawing attention when encountered later. Attentional capture can be reliably produced in the laboratory, usually by paying participants money for finding certain targets in a visual search task (Anderson, Laurent, & Yantis, 2011). We have recently shown that attentional capture can also be produced by presenting tasks in a videogame-like format, with points and sound effects serving as the rewards in place of money (Miranda & Palmer, 2014). In the current study, we apply gamified attentional capture training to the automatic processing of target shapes rather than target colors. Participants were rewarded for locating certain shapes in a training phase and then in a later test phase (during which shape was irrelevant to the task) participants were significantly slower to identify oddball color targets if a previously rewarded shape was present as a distractor. This demonstrates that participants’ visual systems learned to prioritize processing of rewarded shapes and automatically attend to them even when they were irrelevant to the task. Implications of this work for training of socially critical visual search tasks is discussed.

Chitosan has the ability to make injectable thermosensitive hydrogels which has been highly investigated for drug delivery applications. The addition of nanoparticles is one way to increase the mechanical strength of thermosensitive chitosan hydrogel and subsequently and control the burst release of drug. Graphene nanoparticles have shown unique mechanical, optical and electrical properties which can be exploited for biomedical applications, especially in drug delivery. This study, have focused on the mechanical properties of a thermosensitive and injectable hybrid chitosan hydrogel incorporated with graphene nanoparticles. Scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, and X-ray diffraction (XRD) have been used for morphological and chemical characterization of graphene infused chitosan hydrogels. The cell viability and cytotoxicity of graphene-contained hydrogels were analyzed using the alamarBlue® technique. In-vitro methotrexate (MTX) release was investigated from MTX-loaded hybrid hydrogels as well. As a last step, to evaluate their efficiency as a cancer treatment delivery system, an in vitro anti-tumor test was also carried out using MCF-7 breast cancer cell lines. Results confirmed that a thermosensitive chitosan-graphene hybrid hydrogel can be used as a potential breast cancer therapy system for controlled delivery of methotrexate. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2381-2390, 2017.