Abstract
Human neural networks of interconnected neurons have evolved to be remarkably efficient and are capable of learning and memory through the brain’s synaptic plasticity, including short-term plasticity (STP), and long-term potentiation (LTP) and depression (LTD). These activity-dependent mechanisms induce changes in synaptic efficiency over both transient and extended timescales. Understanding the molecular basis of learning and memory is central to deciphering brain function and advancing therapeutics for neurodegenerative diseases. Here, we report that lipid bilayers with embedded gramicidin A ion channels can structurally reorganize when interrogated using a neurologically inspired electrical stimulation protocol, adopting metastable structures with enhanced STP response and emergent LTP or LTD. Specifically, voltage-induced electrocompression is found to restructure membranes, driving them into nonequilibrium steady states with enhanced stability and increased ionic conductivity, leading to stronger and persistent membrane ion conductance. These results show how membrane restructuring and emergent complexity may regulate synaptic plasticity at the molecular level.
| Original language | English |
|---|---|
| Article number | e2510664122 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 122 |
| Issue number | 45 |
| DOIs | |
| State | Published - Nov 11 2025 |
Funding
C.P.C. and J.K. are supported through the Scientific User Facilities Division of the Department of Energy (DOE) Office of Science, sponsored by the Basic Energy Science (BES) Program, DOE Office of Science, under Contract No. DE-AC05-00OR22725. D.B. was supported through the NSF, Division of Molecular and Cellular Biosciences, under contract no. 2219289. R.A. acknowledges partial support from the NSF, Division of Materials Research, under contract no. 2350336. The research was partly funded through the Nonequilibrium and Emergent Transients in Advanced and Soft Materials award, sponsored by the Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the US DOE. P.T.P. was supported through the DOE Omni Technology Alliance Internship Program. P.T.P. and V.S. were supported by the Oak Ridge National Laboratory (ORNL) Research Student Internships program. P.T.P. and O.Z. were supported through the DOE Science Undergraduate Laboratory Internships program. T.K. was partially supported by an ORNL Neutron Scattering Graduate Research Program award. A.A. was supported by a Graduate Education for Minority Students Fellowship. The work was performed at the Center for Nanophase Materials Sciences, a DOE Office of Science User Facility at Oak Ridge National Laboratory sponsored by the Scientific User Facilities Division, Office of BES, US DOE, and the Shull Wollan Center. support from the NSF, Division of Materials Research, under contract no. 2350336. The research was partly funded through the Nonequilibrium and Emergent Transients in Advanced and Soft Materials award, sponsored by the Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, managed by UT-Battelle,LLC,for the US DOE.P.T.P.was supported through the DOE Omni Technology Alliance Internship Program. P.T.P. and V.S. were supported by the Oak Ridge National Laboratory (ORNL) Research Student Internships program. P.T.P. and O.Z. were supported through the DOE Science Undergraduate Laboratory Internships program. T.K. was partially supported by an ORNL Neutron Scattering Graduate Research Program award.A.A.was supported by a Graduate Education for Minority Students Fellowship.The work was performed at the Center for Nanophase Materials Sciences, a DOE Office of Science User Facility at Oak Ridge National Laboratory sponsored by the Scientific User Facilities Division, Office of BES, US DOE, and the Shull Wollan Center. ACKNOWLEDGMENTS. C.P.C. and J.K. are supported through the Scientific User Facilities Division of the Department of Energy (DOE) Office of Science,sponsored by the Basic Energy Science (BES) Program, DOE Office of Science, under Contract No. DE-AC05-00OR22725.D.B.was supported through the NSF,Division of Molecular and Cellular Biosciences, under contract no. 2219289. R.A. acknowledges partial
Keywords
- droplet interface bilayers
- long-term potentiation
- membranes
- neuromorphic materials
- short-term synaptic plasticity