Cameron, H. A., McEwen, B. S. & Gould, E. Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus. J. Neurosci. 15, 4687−4692

Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 07/1995; 15(6):4687-92.
Source: PubMed

ABSTRACT The effects of afferent input and N-methyl-D-aspartate (NMDA) receptor activation on neurogenesis were examined in an intact system, the rat dentate gyrus, where neurons are naturally born in the adult. In the adult dentate gyrus, activation of NMDA receptors rapidly decreased the number of cells synthesizing DNA, whereas blockade of NMDA receptors rapidly increased the number of cells in the S phase identified with 3H-thymidine. Acute treatment with NMDA receptor antagonists increased the birth of neurons and increased the overall density of neurons in the granule cell layer. Lesion of the entorhinal cortex, the main excitatory afferent population to the granule neurons, also increased the birth of cells in the dentate gyrus. These results suggest that adult neurogenesis in the dentate gyrus of the rat is altered by afferent input, via NMDA receptors, and may be regulated naturally by endogenous excitatory amino acids.

Download full-text


Available from: Heather Cameron, Jan 10, 2015
27 Reads
  • Source
    • "Activation of NMDA receptors was shown to rapidly decrease DG cell proliferation, while blockade of the NMDA receptors brought an increase of neurogenesis. When the excitatory input to the DG was severed, an increase in cell proliferation was also observed (Cameron et al. 1995). In a transgenic animal study, it was shown that decreased expression of NR1 subunit of NMDA receptor, which is essential for the ion channel functioning of NMDA, led to an increase in DG neurogenesis (Bursztajn et al. 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Abuse of cough mixture is increasingly prevalent worldwide. Clinical studies showed that chronic consumption of cough mixture at high dosages may lead to psychiatric symptoms, especially affective disturbances, with the underlying mechanisms remain elusive. The present study aims at exploring the effect of repeated, high-dose dextromethorphan (DXM, a common active component of cough mixture) treatment on adult hippocampal neurogenesis, which is associated with pathophysiology of mood disturbances. After treatment with a high-dose of DXM (40 mg/kg/day) for 2 weeks, Sprague-Dawley rats showed increased depression-like behavior when compared to the control animals. Neurogenesis in the hippocampus was suppressed by DXM treatment, which was indicated by decreases in number of proliferative cells and doublecortin (an immature neuron marker)-positive new neurons. Furthermore, the dendritic complexity of the immature neurons was suppressed by DXM treatment. These findings suggest that DXM induces depression- and anxiety-like behavior and suppresses neurogenesis in rats. The current experimental paradigm may serve as an animal model for study on affective effect of cough mixture abuse, rehabilitation treatment options for abusers and the related neurological mechanisms.
    Experimental Brain Research 05/2015; 233(7). DOI:10.1007/s00221-015-4290-0 · 2.04 Impact Factor
  • Source
    • "Gould, with Heather Cameron, also " re-discovered " adult neurogenesis in the dentate gyrus [28] [29], which had been shown previously by Altman [30] and Kaplan [31] but generally disregarded [32]. Like hippocampal remodeling, dentate gyrus neurogenesis is also regulated by both glucocorticoids and excitatory amino acids [33]. However, regarding both dendritic remodeling and postnatal neurogenesis, there remained the task of showing generality across mammalian species. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The discovery of adrenal steroid receptors outside of the hypothalamus in the hippocampus and other forebrain regions catalyzed research on the effects of stress upon cognitive function, emotions and self-regulatory behaviors as well as the molecular, cellular and neuroanatomical mechanisms underlying acute and chronic stress effects on the brain. Indeed, this work has shown that the brain is a plastic and vulnerable organ in the face of acute and chronic stress. The insight that Bob and Caroline Blanchard had in developing and interpreting findings using the Visible Burrow System model made an enormous contribution to the current view that the human brain is very sensitive to the social environment and to agonistic interactions between individuals. Their collaboration with Sakai and McEwen at The Rockefeller University extended application of the Visible Burrow System model to demonstrate that it also was a unique and highly relevant neuroethological model with which to study stress and adaptation to stressors. Those studies focused on the brain and systemic organ responses to stress and, in turn, described that the brain is also very responsive to changes in systemic physiology. Copyright © 2015. Published by Elsevier Inc.
    Physiology & Behavior 04/2015; 146. DOI:10.1016/j.physbeh.2015.04.015 · 2.98 Impact Factor
  • Source
    • "For example, unilateral or bilateral olfactory bulbectomy implies a rapid, transient increase in apoptosis in the dentate gyrus ipsilateral to the removed OB and lesions of the MEC significantly increase the number of dividing cells in the dentate gyrus in adult rats (Pope and Wilson, 2007). Data suggest that afferent input by NMDA receptor activation slows neuronal birth during adulthood (Cameron et al., 1995). Thereby, inputs seem to play a relevant role for cell survival, maturation and integration of new dentate granule cells once they reach maturity. "
    [Show abstract] [Hide abstract]
    ABSTRACT: New neurons are continually generated in the subependymal layer of the lateral ventricles and the subgranular zone of dentate gyrus during adulthood. In the subventricular zone, neuroblasts migrate a long distance to the olfactory bulb where they differentiate into granule or periglomerular interneurons. In the hippocampus, neuroblasts migrate a short distance from the subgranular zone to the granule cell layer of the dentate gyrus to become granule neurons. In addition to the short-distance inputs, bulbar interneurons receive long-distance centrifugal afferents from olfactory-recipient structures. Similarly, dentate granule cells receive differential inputs from the medial and lateral entorhinal cortices through the perforant pathway. Little is known concerning these new inputs on the adult-born cells. In this work, we have characterized afferent inputs to 21-day old newly-born neurons. Mice were intraperitoneally injected with bromodeoxyuridine. Two weeks later, rhodamine-labeled dextran-amine was injected into the anterior olfactory nucleus, olfactory tubercle, piriform cortex and lateral and medial entorhinal cortices. One week later, animals were perfused and immunofluorescences were carried out. The data show that projection neurons from the mentioned structures, establish putative synaptic contacts onto 21-day-old neurons in the olfactory bulb and dentate gyrus, in some cases even before they start to express specific subpopulation proteins. Long-distance afferents reach middle and outer one-third portions of the molecular layer of the dentate gyrus and granule and, interestingly, periglomerular layers of the olfactory bulb. In the olfactory bulb, these fibers appear to establish presumptive axo-somatic contacts onto newly-born granule and periglomerular cells.
    Frontiers in Neuroanatomy 02/2015; 9:4. DOI:10.3389/fnana.2015.00004 · 3.54 Impact Factor
Show more