Adult hippocampal neurogenesis is implicated in a number of disorders where reward processes are disrupted but whether new neurons regulate specific reward behaviors remains unknown. We find that blocking neurogenesis in rats reduces activation of the ventral dentate gyrus and causes a profound aversion for delayed rewards. Delay-based decision-making restructured dendrites and spines in adultborn neurons, consistent with activity-dependent neuronal recruitment. These findings identify a novel role for neurogenesis in decisions about future rewards, which is compromised in disorders where shortsighted gains are preferred at the expense of long-term health. MAIN TEXTAdult neurogenesis in the dentate gyrus (DG) subregion of the hippocampus has been implicated in psychiatric disorders such as depression 1 but it remains unclear exactly which behavioral processes depend on new neurons, due to the complex and heterogeneous nature of the disorder. For example, one of the core symptoms of depression is anhedonia, often defined as diminished pleasure or interest in pleasurable activities 2 . However, many behavioral processes are subsumed under this broad definition 3 . Relative to controls, depressed patients place less value on future rewards, which may shift behaviors away from optimal, but delayed, outcomes 4 . Altered prospective behaviors may result from hippocampal deficits. Indeed, hippocampal activity patterns reflect future-oriented behaviors in both rodents 5-7 and humans 8,9 , amnesics have an impoverished imagination of possible future events 10 and hippocampal damage biases humans 11,12 and animals [13][14][15] towards immediately-available rewards, at the expense of larger, but delayed, rewards. Whether adult neurogenesis contributes to choices about future rewards is unknown. However, blocking neurogenesis in mice reduces sucrose preference 16 , consistent with a possible role in the anhedonic symptoms of depression.To test the role of adult neurogenesis in future reward choice, we took advantage of the transgenic GFAP-TK rat model to deplete neurogenesis 17 , and operant tasks that have been optimized for rats. As measured by the immature neuronal marker, DCX, neurogenesis was reduced in valganciclovirtreated (VGCV) TK rats by 94% in the dorsal DG and 77% in the ventral DG, compared to wild type (WT) rats (Fig. 1A-F). Blockade of neurogenesis reduced the overall volume of the dentate granule cell layer, consistent with DG atrophy in depressed patients 18,19 , but was without noticeable effect on subventricular zone neurogenesis, likely due to faster recovery in this neurogenic region during the VGCV-free period of operant testing (Supplementary Fig. 1 and Supplementary Fig. 2).Delayed rewards typically have less subjective value than immediately-available rewards, a phenomenon often referred to as delay discounting (DD) 20 . To determine if adult neurogenesis regulates the value of delayed rewards, we used a rodent DD paradigm where rats choose between a small reward (1 sugar pellet) that is delivered im...

Background Imagining ways to prevent or treat glioblastoma (GBM) has been hindered by a lack of understanding of its pathogenesis. Although overexpression of platelet derived growth factor with two A-chains (PDGF-AA) may be an early event, critical details of the core biology of GBM are lacking. For example, existing PDGF-driven models replicate its microscopic appearance, but not its genomic architecture. Here we report a model that overcomes this barrier to authenticity. Methods Using a method developed to establish neural stem cell cultures, we investigated the effects of PDGF-AA on subventricular zone (SVZ) cells, one of the putative cells of origin of GBM. We microdissected SVZ tissue from p53-null and wild-type adult mice, cultured cells in media supplemented with PDGF-AA, and assessed cell viability, proliferation, genome stability, and tumorigenicity. Results Counterintuitive to its canonical role as a growth factor, we observed abrupt and massive cell death in PDGF-AA: wild-type cells did not survive, whereas a small fraction of null cells evaded apoptosis. Surviving null cells displayed attenuated proliferation accompanied by whole chromosome gains and losses. After approximately 100 days in PDGF-AA, cells suddenly proliferated rapidly, acquired growth factor independence, and became tumorigenic in immune-competent mice. Transformed cells had an oligodendrocyte precursor-like lineage marker profile, were resistant to platelet derived growth factor receptor alpha inhibition, and harbored highly abnormal karyotypes similar to human GBM. Conclusion This model associates genome instability in neural progenitor cells with chronic exposure to PDGF-AA and is the first to approximate the genomic landscape of human GBM and the first in which the earliest phases of the disease can be studied directly.

The dentate gyrus is essential for remembering the fine details of experiences that comprise episodic memory. Dentate gyrus granule cells receive highly-processed sensory information and are hypothesized to perform a pattern separation function, whereby similar sensory inputs are transformed into orthogonal neural representations. Behaviorally, this is believed to enable distinct memory for highly interfering stimuli. Since the dentate gyrus is comprised of a large number of adult-born neurons, which have unique synaptic wiring and neurophysiological firing patterns, it has been proposed that neurogenesis may contribute to this process in unique ways. Some behavioral evidence exists to support this role, whereby neurogenesis-deficient rodents are impaired at discriminating the fine visuospatial details of experiences. However, the extent to which newborn neurons contribute to dentate gyrus-dependent learning tasks is unclear. Furthermore, since most studies of dentate gyrus function are conducted in male rats, little is known about how females perform in similar situations, and whether there might be sex differences in the function of adult neurogenesis. To address these issues, we examined spatial discrimination memory in transgenic male and female rats that lacked adult neurogenesis. The first task probed memory for the position of local objects in an open field, assessed by behavioral responses to novel object locations. The second task examined memory for distal environmental cues. All rats were able to successfully discriminate local and distal cue changes. Males and females also performed comparably, although females displayed higher levels of rearing and locomotion. Collectively, our results indicate that rats are capable of learning about local and distal cues in the absence of adult neurogenesis.

Objective To synthesize qualitative literature exploring the lived experience of healthcare workers (HCWs) who cared for patients during the following infectious disease outbreaks (IDOs): the 2003 SARS epidemic, 2009 H1N1 pandemic, 2012 MERS outbreak, and 2014 EVD epidemic. We aim to reveal the collective experience of HCWs during these four IDOs and to create a reference for comparison of current and future IDOs. Methods Three electronic databases were searched, yielding 823 results after duplicates were removed. Forty qualitative and mixed-methods studies met the criteria for full file review. Fourteen studies met the inclusion and exclusion criteria. The data from the Results or Findings sections were manually coded and themes were conceptualized using thematic analysis. Results Of the 14 studies, 28.6% focused on SARS, 21.4% on H1N1, 21.4% on MERS, and 28.6% on EVD. Studies occurred in six different countries and included physicians, nurses, paramedics, and emergency medical technicians as participants. Five themes were conceptualized: Uncertainty, Adapting to Change, Commitment, Sacrifice, and Resilience. Conclusion This review identified the collective experience of HCWs caring for patients during four 21st century IDOs. This qualitative systematic review offers a reference to compare similarities and differences of other IDOs, including the COVID-19 pandemic.

Adult hippocampal neurogenesis is implicated in a number of disorders where reward processes are disrupted but whether new neurons regulate specific reward behaviors remains unknown. We find that blocking neurogenesis in rats reduces activation of the ventral dentate gyrus and causes a profound aversion for delayed rewards. Delay-based decision-making restructured dendrites and spines in adultborn neurons, consistent with activity-dependent neuronal recruitment. These findings identify a novel role for neurogenesis in decisions about future rewards, which is compromised in disorders where shortsighted gains are preferred at the expense of long-term health. MAIN TEXTAdult neurogenesis in the dentate gyrus (DG) subregion of the hippocampus has been implicated in psychiatric disorders such as depression 1 but it remains unclear exactly which behavioral processes depend on new neurons, due to the complex and heterogeneous nature of the disorder. For example, one of the core symptoms of depression is anhedonia, often defined as diminished pleasure or interest in pleasurable activities 2 . However, many behavioral processes are subsumed under this broad definition 3 . Relative to controls, depressed patients place less value on future rewards, which may shift behaviors away from optimal, but delayed, outcomes 4 . Altered prospective behaviors may result from hippocampal deficits. Indeed, hippocampal activity patterns reflect future-oriented behaviors in both rodents 5-7 and humans 8,9 , amnesics have an impoverished imagination of possible future events 10 and hippocampal damage biases humans 11,12 and animals 13-15 towards immediately-available rewards, at the expense of larger, but delayed, rewards. Whether adult neurogenesis contributes to choices about future rewards is unknown. However, blocking neurogenesis in mice reduces sucrose preference 16 , consistent with a possible role in the anhedonic symptoms of depression.To test the role of adult neurogenesis in future reward choice, we took advantage of the transgenic GFAP-TK rat model to deplete neurogenesis 17 , and operant tasks that have been optimized for rats. As measured by the immature neuronal marker, DCX, neurogenesis was reduced in valganciclovirtreated (VGCV) TK rats by 94% in the dorsal DG and 77% in the ventral DG, compared to wild type (WT) rats ( Fig. 1A-F). Blockade of neurogenesis reduced the overall volume of the dentate granule cell layer, consistent with DG atrophy in depressed patients 18,19 , but was without noticeable effect on subventricular zone neurogenesis, likely due to faster recovery in this neurogenic region during the VGCV-free period of operant testing ( Supplementary Fig. 1 and Supplementary Fig. 2).Delayed rewards typically have less subjective value than immediately-available rewards, a phenomenon often referred to as delay discounting (DD) 20 . To determine if adult neurogenesis regulates the value of delayed rewards, we used a rodent DD paradigm where rats choose between a small reward (1 sugar pellet) that is delivered immedia...