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The Journal of Neurophysiology Vol. 85 No. 6 June 2001, pp. 2423-2431
Copyright ©2001 by the American Physiological Society
Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
Snyder, J. S.,
N. Kee, and
J. M. Wojtowicz.
Effects of Adult Neurogenesis on Synaptic Plasticity in the Rat
Dentate Gyrus. J. Neurophysiol. 85: 2423-2431, 2001. Ongoing neurogenesis in the adult hippocampal dentate
gyrus (DG) generates a substantial population of young neurons. This phenomenon is present in all species examined thus far, including humans. Although the regulation of adult neurogenesis by various physiologically relevant factors such as learning and stress has been
documented, the functional contributions of the newly born neurons to
hippocampal functions are not known. We investigated possible
contributions of the newly born granule neurons to synaptic plasticity
in the hippocampal DG. In the standard hippocampal slice preparation
perfused with artificial cerebrospinal fluid (ACSF), a small (10%)
long-term potentiation (LTP) of the evoked field potentials is seen
after tetanic stimulation of the afferent medial perforant pathway
(MPP). The induction of this ACSF-LTP is resistant to a
N-methyl-D-aspartate (NMDA) receptor blocker, D,L-2-amino-5-phosphonovaleric acid (APV), but is
completely prevented by ifenprodil, a blocker of NR2B subtype
of NMDA receptors. In contrast, slices perfused with picrotoxin
(PICRO), a GABA-receptor blocker, revealed a larger (40-50%),
APV-sensitive but ifenprodil-insensitive LTP. The ACSF-LTP required
lower frequency of stimulation and fewer stimuli for its induction than
the PICRO-LTP. All these characteristics of ACSF-LTP are in agreement
with the properties of the putative individual new granule neurons
examined previously with the use of the whole cell recording technique
in a similar preparation. A causal relationship between neurogenesis
and ACSF-LTP was confirmed in experiments using low dose of gamma
radiation applied to the brain 3 wk prior to the electrophysiological
experiments. In these experiments, the new cell proliferation was
drastically reduced and ACSF-LTP was selectively blocked. We conclude
that the young, adult-generated granule neurons play a significant role
in synaptic plasticity in the DG. Since DG is the major source of the
afferent inputs into the hippocampus, the production and the plasticity
of new neurons may have an important role in the hippocampal functions
such as learning and memory.
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