title: 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 (approximately 2.8%) than the proportion of cells that expressed Arc in the already existing population of granule cells (approximately 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.
authors.affiliation: Arizona Research Laboratories Division of Neural Systems, Memory, and Aging, University of Arizona, Tucson, Arizona 85724, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Ramirez-Amaya
authors.forename: Diano F
authors.initials: DF
authors.lastname: Marrone
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
authors.forename: Paul F
authors.initials: PF
authors.lastname: Worley
authors.forename: Carol A
authors.initials: CA
authors.lastname: Barnes
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D018613:Microscopy, Confocal / Q000379:methods; D009415:Nerve Net / Q000166:cytology* / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine