Conditional reduction of adult neurogenesis impairs bidirectional hippocampal synaptic plasticity
Proceedings of the National Academy of Sciences. 2011-04-04; 108(16): 6644-6649
DOI: 10.1073/pnas.1016928108
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Erratum in
Proc Natl Acad Sci U S A. 2011 May 10;108(19):8065. Koelh, Muriel [corrected to
Koehl, Muriel].
Adult neurogenesis is a process by which the brain produces new neurons once
development has ceased. Adult hippocampal neurogenesis has been linked to the
relational processing of spatial information, a role attributed to the
contribution of newborn neurons to long-term potentiation (LTP). However, whether
newborn neurons also influence long-term depression (LTD), and how synaptic
transmission and plasticity are affected as they incorporate their network,
remain to be determined. To address these issues, we took advantage of a genetic
model in which a majority of adult-born neurons can be selectively ablated in the
dentate gyrus (DG) and, most importantly, in which neurogenesis can be restored
on demand. Using electrophysiological recordings, we show that selective
reduction of adult-born neurons impairs synaptic transmission at medial perforant
pathway synapses onto DG granule cells. Furthermore, LTP and LTD are largely
compromised at these synapses, probably as a result of an increased induction
threshold. Whereas the deficits in synaptic transmission and plasticity are
completely rescued by restoring neurogenesis, these synapses regain their ability
to express LTP much faster than their ability to express LTD. These results
demonstrate that both LTP and LTD are influenced by adult neurogenesis. They also
indicate that as newborn neurons integrate their network, the ability to express
bidirectional synaptic plasticity is largely improved at these synapses. These
findings establish that adult neurogenesis is an important process for synaptic
transmission and bidirectional plasticity in the DG, accounting for its role in
efficiently integrating novel incoming information and in forming new memories.