Integration of New Neurons into Functional Neural Networks

Abstract

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 (ϳ2.8%) than the proportion of cells that expressed Arc in the already existing population of granule cells (ϳ1.6%; p Ͻ 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.

The Endogenous Regenerative Capacity of the Damaged Newborn Brain: Boosting Neurogenesis with Mesenchymal Stem Cell Treatment

“…However, the development of proliferation markers such as [ 3 H]-thymidine or 5-bromo-2 0 -deoxy-uridine (BrdU) during the past decades confirmed the discovery of the existence of proliferating cells in the mature mammalian brain. These studies have indisputably established that neural stem cells (NSCs) from the subgranular zone (SGZ) in the dentate gyrus of the hippocampus and the subventricular zone (SVZ) in the lateral ventricles continue to proliferate under normal conditions throughout mammalian adulthood [3][4][5] (see review by Gould 6 ). Evidence from studies in rodents suggests that every month B6% of proliferating cells in the dentate gyrus are functionally integrated into the hippocampus.…”

Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice

“…Cognitive functions, learning and memory, and behavioral health can be improved by increased adult neurogenesis (van Praag et al 2000(van Praag et al , 2005Ramirez-Amaya et al 2006;Deng et al 2010). Additionally, antidepressants function by stimulating adult neurogenesis (Malberg et al 2000;Santarelli et al 2003;Encinas et al 2006;Li et al 2008;Wang et al 2008).…”

Methamphetamine Self-Administration and Voluntary Exercise Have Opposing Effects on Medial Prefrontal Cortex Gliogenesis

“…The ability of the brain to endlessly generate new precursor or neural stem cells throughout adulthood that maintain the structure and function of the adult mammalian brain changed the dogma that new neurons were born only during development (Gould et al, 1999a;Markakis and Gage, 1999;Kempermann, 2002;van Praag et al, 2002;Ramirez-Amaya et al, 2006). Medial prefrontal cortex (mPFC) precursors are mostly gliogenic, and their neurogenic capacity is uncertain and unconfirmed (Gould et al, 1999b;Magavi et al, 2000;Nowakowski and Hayes, 2000;Kornack and Rakic, 2001;Bernier et al, 2002;Ehninger and Kempermann, 2003;Koketsu et al, 2003;Kodama et al, 2004;Dayer et al, 2005;Madsen et al, 2005;Czeh et al, 2007;Ongur et al, 2007).…”