Control of CA3 Output by Feedforward Inhibition Despite Developmental Changes in the Excitation-Inhibition Balance
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Torborg-2010-Control of CA3 Output by Feedforward Inhibition Despite Developmental Changes in the Excitation-Inhibition Balance.pdf
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Author(s)
Torborg, Christine L.
Nakashiba, Toshiaki
Tonegawa, Susumu
McBain, Chris J.
Date Issued
November 2010
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Torborg, C. L. et al. “Control of CA3 Output by Feedforward Inhibition Despite Developmental Changes in the Excitation-Inhibition Balance.” Journal of Neuroscience 30.46 (2010) : 15628-15637. Copyright © 2010 the authors
Version
Final published version
Abstract
In somatosensory cortex, the relative balance of excitation and inhibition determines how effectively feedforward inhibition enforces the
temporal fidelity of action potentials. Within the CA3 region of the hippocampus, glutamatergic mossy fiber (MF) synapses onto CA3
pyramidal cells (PCs) provide strong monosynaptic excitation that exhibit prominent facilitation during repetitive activity. We demonstrate
in the juvenile CA3 that MF-driven polysynaptic IPSCs facilitate to maintain a fixed EPSC-IPSC ratio during short-term plasticity.
In contrast, in young adult mice this MF-driven polysynaptic inhibitory input can facilitate or depress in response to short trains of
activity. Transgenic mice lacking the feedback inhibitory loop continue to exhibit both facilitating and depressing polysynaptic IPSCs,
indicating that this robust inhibition is not caused by the secondary engagement of feedback inhibition. Surprisingly, eliminating
MF-driven inhibition onto CA3 pyramidal cells by blockade of GABAA [GABA subscript A] receptors did not lead to a loss of temporal precision of the first
action potential observed after a stimulus but triggered in many cases a long excitatory plateau potential capable of triggering repetitive
action potential firing. These observations indicate that, unlike other regions of the brain, the temporal precision of single MF-driven
action potentials is dictated primarily by the kinetics of MF EPSPs, not feedforward inhibition. Instead, feedforward inhibition provides
a robust regulation of CA3 PC excitability across development to prevent excessive depolarization by the monosynaptic EPSP and
multiple action potential firings.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Picower Institute for Learning and Memory
RIKEN-MIT Center for Neural Circuit Genetics
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DOI of Published Version
https://doi.org/10.1523/jneurosci.3099-10.2010
