Distinct protein synthesis requirements for coupled excitatory and inhibitory long-term co-plasticity in mouse hippocampus
- 1Wroclaw Medical University
Abstract
The functioning of neuronal networks critically depends on the coordinated interaction between excitation and inhibition. The properties of glutamatergic and GABAergic synapses are finely tuned by network activity, and the heterosynaptic nature of inhibitory plasticity further emphasizes their functional coupling. Although the dependence of glutamatergic plasticity on protein synthesis is well established, the role of translation in inhibitory plasticity remains unclear. Herein, we investigated how protein synthesis supports the concurrent plasticity at inhibitory and excitatory inputs onto CA1 pyramidal neurons. To this end, we applied a high-frequency stimulation protocol of CA3-CA1 input combined with prolonged postsynaptic depolarization of principal cells. This induced both glutamatergic long-term potentiation (LTP) and inhibitory LTP (iLTP) at synapses formed by somatostatin-expressing interneurons onto pyramidal neurons. Although LTP was observed in slices from both juvenile ([≤]45 days) and adult (>45 days) mice, iLTP was only present in the adult group, revealing an unusual developmental profile. Moreover, in adult animals, excitatory LTP was required for the induction of iLTP but did not determine its magnitude. We found that bath application of translation inhibitor cycloheximide (CHX) strongly attenuated LTP and converted co-occurring iLTP into iLTD. However, when CHX was restricted to the recorded postsynaptic neuron, the initial phase of iLTP proceeded normally, but GABAergic currents gradually returned to baseline levels, indicating intact induction but impaired maintenance. In contrast, postsynaptic CHX left excitatory LTP unaffected. Together, these findings identify two distinct translational mechanisms: a postsynaptic one necessary for strengthening inhibition and a non-postsynaptic process required to potentiate excitation.
Versions
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BibTeX
@misc{jablonska2026distinct,
title = {{Distinct protein synthesis requirements for coupled excitatory and inhibitory long-term co-plasticity in mouse hippocampus}},
author = {J. Jablonska and D. Orzol and D. Ciurko and G. Wiera and J. W. Mozrzymas},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.15.751693},
url = {https://www.biorxiv.org/content/10.64898/2026.09.15.751693v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Distinct protein synthesis requirements for coupled excitatory and inhibitory long-term co-plasticity in mouse hippocampus
AU - J. Jablonska
AU - D. Orzol
AU - D. Ciurko
AU - G. Wiera
AU - J. W. Mozrzymas
PY - 2026
DA - 2026/09/15
PB - bioRxiv
DO - 10.64898/2026.09.15.751693
UR - https://www.biorxiv.org/content/10.64898/2026.09.15.751693v1
AB - The functioning of neuronal networks critically depends on the coordinated interaction between excitation and inhibition. The properties of glutamatergic and GABAergic synapses are finely tuned by network activity, and the heterosynaptic nature of inhibitory plasticity further emphasizes their functional coupling. Although the dependence of glutamatergic plasticity on protein synthesis is well established, the role of translation in inhibitory plasticity remains unclear. Herein, we investigated how protein synthesis supports the concurrent plasticity at inhibitory and excitatory inputs onto CA1 pyramidal neurons. To this end, we applied a high-frequency stimulation protocol of CA3-CA1 input combined with prolonged postsynaptic depolarization of principal cells. This induced both glutamatergic long-term potentiation (LTP) and inhibitory LTP (iLTP) at synapses formed by somatostatin-expressing interneurons onto pyramidal neurons. Although LTP was observed in slices from both juvenile ([≤]45 days) and adult (>45 days) mice, iLTP was only present in the adult group, revealing an unusual developmental profile. Moreover, in adult animals, excitatory LTP was required for the induction of iLTP but did not determine its magnitude. We found that bath application of translation inhibitor cycloheximide (CHX) strongly attenuated LTP and converted co-occurring iLTP into iLTD. However, when CHX was restricted to the recorded postsynaptic neuron, the initial phase of iLTP proceeded normally, but GABAergic currents gradually returned to baseline levels, indicating intact induction but impaired maintenance. In contrast, postsynaptic CHX left excitatory LTP unaffected. Together, these findings identify two distinct translational mechanisms: a postsynaptic one necessary for strengthening inhibition and a non-postsynaptic process required to potentiate excitation.
ER -