Heterogeneous off-target impact of ion-channel deletion on intrinsic properties of hippocampal model neurons that self-regulate calcium DOI Creative Commons
Sunandha Srikanth, Rishikesh Narayanan

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Oct. 10, 2023

How do neurons that implement cell-autonomous self-regulation of calcium react to knockout individual ion-channel conductances? To address this question, we used a heterogeneous population 78 conductance-based models hippocampal pyramidal maintained homeostasis while receiving theta-frequency inputs. At steady-state, individually deleted each the 11 active conductances from model. We measured acute impact deleting conductance (one at time) by comparing intrinsic electrophysiological properties before and immediately after channel deletion. The on physiological (including homeostasis) was heterogeneous, depending property, specific model, channel. underlying many-to-many mapping between ion channels pointed degeneracy. Next, allowed other (barring conductance) evolve towards achieving during activity. When perturbed deletion, post-knockout plasticity in ensured resilience These results demonstrate degeneracy homeostasis, as implemented absence earlier involved homeostatic process. Importantly, reacquiring underwent heterogenous (dependent channel), even introducing changes were not directly connected Together, geared maintaining introduced off-target effects several properties, suggesting extreme caution be exercised interpreting experimental outcomes involving knockouts.

Language: Английский

Different parameter solutions of a conductance-based model that behave identically are not necessarily degenerate DOI
Loïs Naudin

Journal of Computational Neuroscience, Journal Year: 2023, Volume and Issue: 51(2), P. 201 - 206

Published: March 11, 2023

Citations

2

Heterogeneous off-target impact of ion-channel deletion on intrinsic properties of hippocampal model neurons that self-regulate calcium DOI Creative Commons
Sunandha Srikanth, Rishikesh Narayanan

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Oct. 10, 2023

How do neurons that implement cell-autonomous self-regulation of calcium react to knockout individual ion-channel conductances? To address this question, we used a heterogeneous population 78 conductance-based models hippocampal pyramidal maintained homeostasis while receiving theta-frequency inputs. At steady-state, individually deleted each the 11 active conductances from model. We measured acute impact deleting conductance (one at time) by comparing intrinsic electrophysiological properties before and immediately after channel deletion. The on physiological (including homeostasis) was heterogeneous, depending property, specific model, channel. underlying many-to-many mapping between ion channels pointed degeneracy. Next, allowed other (barring conductance) evolve towards achieving during activity. When perturbed deletion, post-knockout plasticity in ensured resilience These results demonstrate degeneracy homeostasis, as implemented absence earlier involved homeostatic process. Importantly, reacquiring underwent heterogenous (dependent channel), even introducing changes were not directly connected Together, geared maintaining introduced off-target effects several properties, suggesting extreme caution be exercised interpreting experimental outcomes involving knockouts.

Language: Английский

Citations

2