Memory consists of several separate entities that depend on various brain systems [1]. Clinical and behavioral evidence suggests that the hippocampus and the surrounding anatomically associated regions serve a critical role in learning and memory [2]. In the 1960s, the outlines of the essential neural substrates of memory were gradually elucidated based on analyzing the effects of therapeutic surgical lesions of the bilateral medial temporal lobes to suppress uncontrollable epilepsy in a patient [3]. Although the operation was effective in controlling the patient's epilepsy, one unexpected consequence was that he became profoundly amnesic while retaining his intelligence and perceptual and motor functions. Similar cases were also seen in other patients with damage to the hippocampal formation and surrounding medial temporal lobe structures [4]. These individuals had severe amnesia for episodic events, although other forms of learning and memory-semantic, perceptual, procedural, and simple forms of conditioning-were spared. It is now believed that the hippocampal formation has a central role in declarative memory, the ability to recollect everyday facts and events consciously [5]. The unique anatomy, electrophysiologic characteristics, and key roles in memory formation have made the hippocampus an attractive target of research for neuroscientists.For decades, it was believed that neurogenesis only occurred during embryonic stages in the mammalian central nervous system (CNS), making the brain one of the few mammalian organs incapable of replenishing its functional cell population throughout life [6]. In the 1960s, seminal studies by Altman and Das [7][8][9] provided the first evidence that new neurons were generated in the postnatal mammalian brain. In 1992, Reynolds and Weiss [10] isolated multipotent neural stem/progenitor cells (NSCs) from the adult rodent brain and characterized them in vitro. Studies in the 1990s confirmed that, contrary to long-held dogma, NSCs reside in the adult CNS and active neurogenesis occurs in discrete regions of the adult brain across various mammalian species, including mice, rats, monkeys, and humans [11][12][13][14]. Only recently has it been recognized that adult neurogenesis replicates the complex process of neuronal development to generate functionally integrated new neurons ( Fig. 1) [15][16][17]. A role for these postnatally generated cells in learning was first suggested by Altman and Das in the 1960s [7-9,18]. Later, Nottebohm [19] directly tested the role of * Corresponding author: shongju1@jhmi.edu (H. Song).
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Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript adult-generated neurons in song learning in birds. Subsequent work in rodents has led to the idea that adult neurogenesis is important for learning and memory of spatial information.The discovery of adult neurogenesis has generated significant interest, especially in regard to the hippocampus, not only for neuroscientists but for physicians who are engaged in treating various ...