Integration of New Neurons into Functional Neural Networks

By V. Ramírez-Amaya, D. Marrone, Fred H. Gage, P. Worley, C. A. Barnes. 2006

359 citations recorded by the source corpus.

Although it is established that new granule cells can be born and can survive in the adult mammalian hippocampus, there remains some question concerning the functional integration of these neurons into behaviorally relevant neural networks. By using high-resolution confocal microscopy, we have applied a new strategy to address the question of functional integration of newborn neurons into networks that mediate spatial information processing and memory formation. Exploration-induced expression of the immediate-early gene Arc in hippocampal cells has been linked to cellular activity observed in electrophysiological recordings under the same behavioral conditions. We investigated whether mature (5-month-old), newborn granule cells express Arc in response to a discrete spatial experience by detecting the expression of Arc in combination with NeuN (neuron-specific nuclear protein)-positive and bromodeoxyuridine-positive cells. We found that mature new granule cells do indeed express Arc in response to an exploration experience, supporting the idea that these cells are well integrated into hippocampal circuits. The proportion of mature newborn neurons that expressed Arc in response to exploration, however, was significantly higher (∼2.8%) than the proportion of cells that expressed Arc in the already existing population of granule cells (∼1.6%; p < 0.01). This finding extends previous data suggesting that the cellular physiology of newborn granule neurons differs from that of the existing population by indicating that these properties are retained in mature adult-generated neurons. Thus, these data have interesting implications for network models of spatial information processing and the role of hippocampal circuits in memory, indicating that mature new neurons are selectively recruited into hippocampal cell assemblies in higher proportions than older cells.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Developmental Neuroscience

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

In Cognitive Neuroscience

In Developmental Neuroscience

Citations in the corpus

Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “First, adult-born neurons are preferentially activated by specific inputs as indicated by immediate early gene expression in both hippocampus (Kee et al., 2007; Ramirez-Amaya et al., 2006) and olfactory bulb (Belnoue et al.”
New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? (2010, background): “Compared with their mature counterparts, a higher proportion of 5-month-old adult-born DGCs expressed IEGs when rats were allowed to encounter and explore a novel environmen”
Distinct Determinants of Sparse Activation during Granule Cell Maturation (2013, background): “…It is well established that the DG uses sparse population coding with only a small percentage of GCs activated in response to physiological stimuli (Jung and McNaughton, 1993; Chawla et al., 2005; Ramirez-Amaya et al., 2006; Kee et al., 2007; Stone et al., 2011; Neunuebel and Knierim, 2012).”
Emerging roles of Wnts in the adult nervous system (2010, background): “Wnt signalling in non-neurogenic regions The finding that new neurons functionally integrate into adult brain circuit”
A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. (2007, neutral): “Recent studies using c-Fos and Arc expression as indicators for neuronal activation suggest an interesting possibility that new DGCs may be preferentially recruited into circuits in the adult brain that mediate spatial information processing and memory formation (Kee et al., 2007; Ramirez-Amaya et a”
Experience dictates stem cell fate in the adult hippocampus. (2011, neutral): “Moreover, baseline differences in neuronal activity were described between the upper (more active) and lower (less active) blades of the dentate gyrus (Ramirez-Amaya et al., 2006).”
Spatial Learning Depends on Both the Addition and Removal of New Hippocampal Neurons (2007, background): “although spatial behaviors preferentially activated new neurons in the dentate gyrus [50,51], this recruitment did”
Hippocampal granule cells opt for early retirement (2010, methodology): “The volume of the granular cell layer was calculated from the reference image, and the total number of granule cells was estimated, as described previously (Chawla et al., 2005; Ramirez-Amaya et al., 2005, 2006).”
A Critical Time Window for the Recruitment of Bulbar Newborn Neurons by Olfactory Discrimination Learning (2011, methodology): “Recruitment of newborn neurons by odor stimulation By imaging the activation of 2-, 5-, and 9-week-old neurons using a classical functional anatomical approach (Jessberger and Kempermann, 2003; Ramirez-Amaya et al., 2006; Kee et al., 2007; Tashiro et al., 2007; Trouche et al., 2009), we found that o”
How widespread is adult neurogenesis in mammals? (2007, result): “This study was a turning point in the field as it stimulated many investigations in experimental animals which produced further data regarding the neuronal identity of the new cell”
Recruitment of adult-generated neurons into functional hippocampal networks contributes to updating and strengthening of spatial memory (2009, background): “Recently, it was found that new cells contribute to the functional activity patterns elicited in the hippocampus in response to performing memory tasks that solicit hippocampal networks (4, 6, 7).”
Development of neural stem cell in the adult brain. (2008, background): “One hypothesis is that new neurons are preferentially incorporated into special circuitry to support specific brain functions, as suggested by findings based on the expression of immediate early genes such as Arc and c-Fos [42 ,43,44].”
Modification of hippocampal circuitry by adult neurogenesis (2012, background): “, 2007), which may facilitate integration in order to achieve long-term changes in the network (Ramirez-Amaya et al., 2006; Wiskott et al., 2006).”