Knockdown of the glucocorticoid receptor alters functional integration of newborn neurons in the adult hippocampus and impairs fear-motivated behavior

2012 ◽  
Vol 18 (9) ◽  
pp. 993-1005 ◽  
Author(s):  
C P Fitzsimons ◽  
L W A van Hooijdonk ◽  
M Schouten ◽  
I Zalachoras ◽  
V Brinks ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Functional Integration ◽  
Motivated Behavior ◽  
Adult Hippocampus ◽  
Newborn Neurons

scholarly journals microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus

2010 ◽  
Vol 107 (47) ◽  
pp. 20382-20387 ◽  
Author(s):  
S. T. Magill ◽  
X. A. Cambronne ◽  
B. W. Luikart ◽  
D. T. Lioy ◽  
B. H. Leighton ◽  
...  
Keyword(s):  
Dendritic Growth ◽  
Adult Hippocampus ◽  
Newborn Neurons

scholarly journals Adult dentate gyrus neurogenesis: a functional model

2019 ◽  
Author(s):  
Olivia Gozel ◽  
Wulfram Gerstner
Keyword(s):  
Theoretical Model ◽  
Dentate Gyrus ◽  
Granule Cells ◽  
Functional Integration ◽  
Functional Model ◽  
Behavioral Pattern ◽  
Pattern Separation ◽  
Cell Maturation ◽  
Newborn Cell ◽  
Newborn Neurons

SummaryIn adult dentate gyrus neurogenesis, the link between maturation of newborn neurons and their function, such as behavioral pattern separation, has remained puzzling. By analyzing a theoretical model, we show that the switch from excitation to inhibition of the GABAergic input onto maturing newborn cells is crucial for their proper functional integration. When the GABAergic input is excitatory, cooperativity drives the growth of synapses such that newborn cells become sensitive to stimuli similar to those that activate mature cells. When GABAergic input switches to inhibitory, competition pushes the configuration of synapses onto newborn cells towards stimuli that are different from previously stored ones. This enables the maturing newborn cells to code for concepts that are novel, yet similar to familiar ones. Our theory of newborn cell maturation explains both how adult-born dentate granule cells integrate into the preexisting network and why they promote separation of similar but not distinct patterns.

scholarly journals The transcription factor ZEB1 regulates stem cell self-renewal and astroglial fate in the adult hippocampus

2020 ◽  
Author(s):  
B Gupta ◽  
AC Errington ◽  
S Brabletz ◽  
MP Stemmler ◽  
T Brabletz ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Radial Glia ◽  
Lineage Specification ◽  
Self Renewal ◽  
Cell Divisions ◽  
E Box ◽  
Genetic Deletion ◽  
Adult Hippocampus ◽  
Newborn Neurons

AbstractRadial glia-like (RGL) cells persist in the adult mammalian hippocampus where they give rise to new neurons and astrocytes throughout life. Many studies have investigated the process of adult neurogenesis, but factors deciding between neuronal and astroglial fate are incompletely understood. Here, we evaluate the functions of the transcription factor zinc finger E-box binding homeobox 1 (ZEB1) in adult hippocampal RGL cells using a conditional-inducible mouse model. We find that ZEB1 is necessary for self-renewal of active RGL cells as well as for astroglial lineage specification. Genetic deletion of Zeb1 causes differentiation-coupled depletion of RGL cells resulting in an increase of newborn neurons at the expense of newly generated astrocytes. This is due to a shift towards symmetric cell divisions that consume the RGL cell and generate pro-neuronal progenies. We identify ZEB1 as a regulator of stem cell self-renewal and lineage specification in the adult hippocampus.

Survival of newborn neurons in the adult hippocampus is enhanced by Bcl-2 overexpression in normal and ischemic conditions

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S450-S450
Author(s):  
Tsutomu Sasaki ◽  
Kazuo Kitagawa ◽  
Yoshiki Yagita ◽  
Emi Omura-Matsuoka ◽  
Shiro Sugiura ◽  
...  
Keyword(s):  
Adult Hippocampus ◽  
Newborn Neurons

scholarly journals Zif268/egr1 gene controls the selection, maturation and functional integration of adult hippocampal newborn neurons by learning

2013 ◽  
Vol 110 (17) ◽  
pp. 7062-7067 ◽  
Author(s):  
A. Veyrac ◽  
A. Gros ◽  
E. Bruel-Jungerman ◽  
C. Rochefort ◽  
F. B. Kleine Borgmann ◽  
...  
Keyword(s):  
Functional Integration ◽  
Newborn Neurons

scholarly journals Learning Increases the Survival of Newborn Neurons Provided That Learning Is Difficult to Achieve and Successful

2011 ◽  
Vol 23 (9) ◽  
pp. 2159-2170 ◽  
Author(s):  
Daniel M. Curlik ◽  
Tracey J. Shors
Keyword(s):  
Nmda Receptor ◽  
Hippocampal Formation ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Adult Hippocampus ◽  
Newborn Neurons ◽  
Pharmacological Manipulations ◽  
Task Parameters ◽  
Nmda Receptor Activation ◽  
Number Of Cells

Learning increases neurogenesis by increasing the survival of new cells generated in the adult hippocampal formation [Shors, T. J. Saving new brain cells. Scientific American, 300, 46–52, 2009]. However, only some types of learning are effective. Recent studies demonstrate that animals that learn the conditioned response (CR) but require more trials to do so retain more new neurons than animals that quickly acquire the CR or that fail to acquire the CR. In these studies, task parameters were altered to modify the number of trials required to learn a CR. Here, we asked whether pharmacological manipulations that prevent or facilitate learning would decrease or increase, respectively, the number of cells that remain in the hippocampus after training. To answer this question, we first prevented learning with the competitive N-methyl-d-aspartate (NMDA) receptor antagonist (RS)-3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid. As a consequence, training did not increase cell survival. Second, we facilitated learning with the cognitive enhancer d-cycloserine, which increases NMDA receptor activity via its actions at the glycine binding site. Administration of d-cycloserine each day before training increased the number of learned responses and the number of cells that survived. All animals that learned the CR retained more of the new cells, but those that learned very quickly retained fewer than those that required more training trials to learn. Together, these results demonstrate that NMDA receptor activation modifies learning and as a consequence alters the number of surviving cells in the adult hippocampus.

scholarly journals A functional model of adult dentate gyrus neurogenesis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Olivia Gozel ◽  
Wulfram Gerstner
Keyword(s):  
Theoretical Model ◽  
Dentate Gyrus ◽  
Granule Cells ◽  
Functional Integration ◽  
Functional Model ◽  
Behavioral Pattern ◽  
Pattern Separation ◽  
Cell Maturation ◽  
Newborn Cell ◽  
Newborn Neurons

In adult dentate gyrus neurogenesis, the link between maturation of newborn neurons and their function, such as behavioral pattern separation, has remained puzzling. By analyzing a theoretical model, we show that the switch from excitation to inhibition of the GABAergic input onto maturing newborn cells is crucial for their proper functional integration. When the GABAergic input is excitatory, cooperativity drives the growth of synapses such that newborn cells become sensitive to stimuli similar to those that activate mature cells. When GABAergic input switches to inhibitory, competition pushes the configuration of synapses onto newborn cells towards stimuli that are different from previously stored ones. This enables the maturing newborn cells to code for concepts that are novel, yet similar to familiar ones. Our theory of newborn cell maturation explains both how adult-born dentate granule cells integrate into the preexisting network and why they promote separation of similar but not distinct patterns.

Evaluating the functional state of adult-born neurons in the adult dentate gyrus of the hippocampus: from birth to functional integration

2015 ◽  
Vol 26 (3) ◽  
Author(s):  
Andrea Aguilar-Arredondo ◽  
Clorinda Arias ◽  
Angélica Zepeda
Keyword(s):  
Dentate Gyrus ◽  
Functional State ◽  
Functional Integration ◽  
Critical Time ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Maturation Stage ◽  
Methodological Approaches ◽  
Adult Born Neurons ◽  
Newborn Neurons

AbstractHippocampal neurogenesis occurs in the adult brain in various species, including humans. A compelling question that arose when neurogenesis was accepted to occur in the adult dentate gyrus (DG) is whether new neurons become functionally relevant over time, which is key for interpreting their potential contributions to synaptic circuitry. The functional state of adult-born neurons has been evaluated using various methodological approaches, which have, in turn, yielded seemingly conflicting results regarding the timing of maturation and functional integration. Here, we review the contributions of different methodological approaches to addressing the maturation process of adult-born neurons and their functional state, discussing the contributions and limitations of each method. We aim to provide a framework for interpreting results based on the approaches currently used in neuroscience for evaluating functional integration. As shown by the experimental evidence, adult-born neurons are prone to respond from early stages, even when they are not yet fully integrated into circuits. The ongoing integration process for the newborn neurons is characterised by different features. However, they may contribute differently to the network depending on their maturation stage. When combined, the strategies used to date convey a comprehensive view of the functional development of newly born neurons while providing a framework for approaching the critical time at which new neurons become functionally integrated and influence brain function.

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