Hippocampal neurogenesis promotes preference for future rewards

ABSTRACTAdult 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 adult-born 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 short-sighted gains are preferred at the expense of long-term health.

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Capicua regulates the development of adult-born neurons in the hippocampus

Scientific Reports ◽

10.1038/s41598-021-91168-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Brenna Hourigan ◽

Spencer D. Balay ◽

Graydon Yee ◽

Saloni Sharma ◽

Qiumin Tan

Keyword(s):

Dentate Gyrus ◽

Progenitor Cells ◽

Neural Progenitor Cells ◽

Neural Progenitor Cell ◽

Neural Progenitor ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Proliferative Potential ◽

Cell Pool ◽

Adult Born Neurons

AbstractNew neurons continuously arise from neural progenitor cells in the dentate gyrus of the adult hippocampus to support ongoing learning and memory formation. To generate functional adult-born neurons, neural progenitor cells proliferate to expand the precursor cell pool and differentiate into neurons. Newly generated cells then undergo postmitotic maturation to migrate to their final destination and develop elaborate dendritic branching, which allows them to receive input signals. Little is known about factors that regulate neuronal differentiation, migration, and dendrite maturation during adult hippocampal neurogenesis. Here, we show that the transcriptional repressor protein capicua (CIC) exhibits dynamic expression in the adult dentate gyrus. Conditional deletion of Cic from the mouse dentate gyrus compromises the adult neural progenitor cell pool without altering their proliferative potential. We further demonstrate that the loss of Cic impedes neuronal lineage development and disrupts dendritic arborization and migration of adult-born neurons. Our study uncovers a previously unrecognized role of CIC in neurogenesis of the adult dentate gyrus.

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Sex Differences in Maturation and Attrition of Adult Neurogenesis in the Hippocampus

10.1101/726398 ◽

2019 ◽

Cited By ~ 1

Author(s):

Shunya Yagi ◽

Jared E.J. Splinter ◽

Daria Tai ◽

Sarah Wong ◽

Yanhua Wen ◽

...

Keyword(s):

Sex Differences ◽

Dentate Gyrus ◽

Adult Neurogenesis ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Female Rats ◽

Sprague Dawley ◽

Male And Female Rats ◽

Maturation Rate ◽

Adult Born Neurons

ABSTRACTSex differences exist in the regulation of adult neurogenesis in the hippocampus in response to hormones and cognitive training. Here we investigated the trajectory and maturation rate of adult-born neurons in the dentate gyrus (DG) of male and female rats. Sprague-Dawley rats were perfused two hours, 24 hours, one, two or three weeks after BrdU injection, a DNA synthesis marker that labels dividing progenitor cells and their progeny. Adult-born neurons (BrdU/NeuN-ir) matured faster in males compared to females. Males had a greater density of neural stem cells (Sox2-ir) in the dorsal, but not in the ventral, DG and had higher levels of cell proliferation (Ki67-ir) than non-proestrous females. However, males showed a greater reduction in neurogenesis between one and two weeks after mitosis, whereas females showed similar levels of neurogenesis throughout the weeks. The faster maturation and greater attrition of new neurons in males compared to females suggests greater potential for neurogenesis to respond to external stimuli in males and emphasizes the importance of studying sex on adult hippocampal neurogenesis.Significance StatementPreviously studies examining the characteristics of adult-born neurons in the dentate gyrus have used almost exclusively male subjects. Researchers have assumed the two sexes have a similar maturation and attrition of new neurons in the dentate gyrus of adults. However, this study highlights notable sex differences in the attrition, maturation rate and potential of neurogenesis in the adult hippocampus that has significant implications for the field of neuroplasticity. These findings are important in understanding the relevance of sex differences in the regulation of neurogenesis in the hippocampus in response to stimuli or experience and may have consequences for our understanding of diseases that involve neurodegeneration of the hippocampus, particularly those that involve sex differences, such as Alzheimer’s disease and depression.

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Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury

Current Medicinal Chemistry ◽

10.2174/0929867328666210923143713 ◽

2021 ◽

Vol 28 ◽

Author(s):

Lucas Alexandre Santos Marzano ◽

Fabyolla Lúcia Macedo de Castro ◽

Caroline Amaral Machado ◽

João Luís Vieira Monteiro de Barros ◽

Thiago Macedo e Cordeiro ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Clinical Studies ◽

Molecular Mechanisms ◽

Hippocampal Neurogenesis ◽

Cognitive Outcomes ◽

Adult Hippocampal Neurogenesis ◽

The Brain

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

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Heterosynaptic NMDA Receptor Plasticity in Hippocampal Dentate Granule Cells

10.1101/2022.01.12.476040 ◽

2022 ◽

Author(s):

Alma Rodenas-Ruano ◽

Kaoutsar Nasrallah ◽

Stefano Lutzu ◽

Maryann Castillo ◽

Pablo E. Castillo

Keyword(s):

Dentate Gyrus ◽

Entorhinal Cortex ◽

Information Transfer ◽

Granule Cells ◽

Hippocampal Slices ◽

Dentate Granule Cells ◽

Hippocampus Proper ◽

Receptor Plasticity ◽

Activity Dependent

The dentate gyrus is a key relay station that controls information transfer from the entorhinal cortex to the hippocampus proper. This process heavily relies on dendritic integration by dentate granule cells (GCs) of excitatory synaptic inputs from medial and lateral entorhinal cortex via medial and lateral perforant paths (MPP and LPP, respectively). N-methyl-D-aspartate receptors (NMDARs) can contribute significantly to the integrative properties of neurons. While early studies reported that excitatory inputs from entorhinal cortex onto GCs can undergo activity-dependent long-term plasticity of NMDAR-mediated transmission, the input-specificity of this plasticity along the dendritic axis remains unknown. Here, we examined the NMDAR plasticity rules at MPP-GC and LPP-GC synapses using physiologically relevant patterns of stimulation in acute rat hippocampal slices. We found that MPP-GC, but not LPP-GC synapses, expressed homosynaptic NMDAR-LTP. In addition, induction of NMDAR-LTP at MPP-GC synapses heterosynaptically potentiated distal LPP-GC NMDAR plasticity. The same stimulation protocol induced homosynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-LTP at MPP-GC but heterosynaptic AMPAR-LTD at distal LPP synapses, demonstrating that NMDAR and AMPAR are governed by different plasticity rules. Remarkably, heterosynaptic but not homosynaptic NMDAR-LTP required Ca2+ release from intracellular, ryanodine-dependent Ca2+ stores. Lastly, the induction and maintenance of both homo- and heterosynaptic NMDAR-LTP were blocked by GluN2D antagonism, suggesting the recruitment of GluN2D-containing receptors to the synapse. Our findings uncover a mechanism by which distinct inputs to the dentate gyrus may interact functionally and contribute to hippocampal-dependent memory formation.

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Canonical Wnt-signaling modulates the tempo of dendritic growth of adult-born hippocampal neurons

10.1101/2020.01.14.905919 ◽

2020 ◽

Author(s):

Jana Heppt ◽

Marie-Theres Wittmann ◽

Jingzhong Zhang ◽

Daniela Vogt-Weisenhorn ◽

Nilima Prakash ◽

...

Keyword(s):

Young Adult ◽

Wnt Signaling ◽

Progenitor Cells ◽

Dendritic Growth ◽

Functional Integration ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Canonical Wnt Signaling ◽

Adult Born Neurons ◽

Canonical Wnt

AbstractIn adult hippocampal neurogenesis neural stem/progenitor cells generate new dentate granule neurons that contribute to hippocampal plasticity. The establishment of a morphologically defined dendritic arbor is central to the functional integration of adult-born neurons. Here, we investigated the role of canonical Wnt/β-catenin-signaling in dendritogenesis of adult-born neurons. We show that canonical Wnt-signaling follows a biphasic pattern, with high activity in stem/progenitor cells, attenuation in early immature neurons, and re-activation during maturation, and demonstrate that the biphasic activity pattern is required for proper dendrite development. Increasing β-catenin-signaling in maturing neurons of young adult mice transiently accelerated dendritic growth, but eventually resulted in dendritic defects and excessive spine numbers. In middle-aged mice, in which protracted dendrite and spine development was paralleled by lower canonical Wnt-signaling activity, enhancement of β-catenin-signaling restored dendritic growth and spine formation to levels observed in young adult animals. Our data indicate that precise timing and strength of β-catenin-signaling is essential for the correct functional integration of adult-born neurons and suggest Wnt/β-catenin-signaling as a pathway to ameliorate deficits in adult neurogenesis during aging.

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Activity-Dependent Regulation of the Early Phase of Adult Hippocampal Neurogenesis

Neurogenesis in the Adult Brain I ◽

10.1007/978-4-431-53933-9_8 ◽

2011 ◽

pp. 217-236 ◽

Cited By ~ 2

Author(s):

Tatsuhiro Hisatsune ◽

Yoko Ide ◽

Rokuya Nochi

Keyword(s):

Early Phase ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Activity Dependent

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Estrogenic Regulation of Hippocampal Neurogenesis Throughout the Lifespan

Estrogens and Memory ◽

10.1093/oso/9780190645908.003.0016 ◽

2020 ◽

pp. 253-281

Author(s):

Shunya Yagi ◽

Rand S. Eid ◽

Wansu Qiu ◽

Paula Duarte-Guterman ◽

Liisa A. M. Galea

Keyword(s):

Steroid Hormones ◽

Cognitive Training ◽

Adult Female ◽

Ovarian Hormones ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Maternal Experience ◽

Number Of Factors ◽

Estrogenic Regulation

Neurogenesis in the hippocampus exists across a number of species, including humans. Steroid hormones, such as estrogens, modulate neurogenesis dependent on age, reproductive experience and sex. Findings are discussed in the chapter with reference to how neurogenesis in the hippocampus is related to learning and memory. Natural fluctuations in ovarian hormones or removal of ovaries modulate neurogenesis in the short term but not in the long term. Maternal experience has long-lasting effects on neurogenesis in the hippocampus. Acute estrogens increase proliferation in adult female rodents, but influence survival of new neurons dependent on a number of factors including sex, cognitive training, type of estrogen, and whether or not cells were produced under estrogens. This chapter outlines findings indicating that estrogens can be strong modulators of adult hippocampal neurogenesis, which may have implications for disorders involving hippocampal dysfunction that target women.

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Metabolic tuning of inhibition regulates hippocampal neurogenesis in the adult brain

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2006138117 ◽

2020 ◽

Vol 117 (41) ◽

pp. 25818-25829

Author(s):

Xinxing Wang ◽

Hanxiao Liu ◽

Johannes Morstein ◽

Alexander J. E. Novak ◽

Dirk Trauner ◽

...

Keyword(s):

Dentate Gyrus ◽

Energy Homeostasis ◽

Inhibitory Neuron ◽

Hippocampal Neurogenesis ◽

Adult Brain ◽

Adult Hippocampal Neurogenesis ◽

Neuron Activity ◽

Adult Mice ◽

Sphingosine 1 Phosphate ◽

Underlying Mechanisms

Hippocampus-engaged behaviors stimulate neurogenesis in the adult dentate gyrus by largely unknown means. To explore the underlying mechanisms, we used tetrode recording to analyze neuronal activity in the dentate gyrus of freely moving adult mice during hippocampus-engaged contextual exploration. We found that exploration induced an overall sustained increase in inhibitory neuron activity that was concomitant with decreased excitatory neuron activity. A mathematical model based on energy homeostasis in the dentate gyrus showed that enhanced inhibition and decreased excitation resulted in a similar increase in neurogenesis to that observed experimentally. To mechanistically investigate this sustained inhibitory regulation, we performed metabolomic and lipidomic profiling of the hippocampus during exploration. We found sustainably increased signaling of sphingosine-1-phosphate, a bioactive metabolite, during exploration. Furthermore, we found that sphingosine-1-phosphate signaling through its receptor 2 increased interneuron activity and thus mediated exploration-induced neurogenesis. Taken together, our findings point to a behavior-metabolism circuit pathway through which experience regulates adult hippocampal neurogenesis.

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