Homeostatic regulation of neuronal function: importance of degeneracy and pleiotropy
Neurons maintain their average firing rate and other properties within narrow bounds despite changing conditions. This homeostatic regulation is achieved using negative feedback to adjust ion channel expression levels. To understand how homeostatic regulation of excitability normally works and how i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1184563/full |
| _version_ | 1797813663273320448 |
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| author | Jane Yang Jane Yang Steven A. Prescott Steven A. Prescott Steven A. Prescott |
| author_facet | Jane Yang Jane Yang Steven A. Prescott Steven A. Prescott Steven A. Prescott |
| author_sort | Jane Yang |
| collection | DOAJ |
| description | Neurons maintain their average firing rate and other properties within narrow bounds despite changing conditions. This homeostatic regulation is achieved using negative feedback to adjust ion channel expression levels. To understand how homeostatic regulation of excitability normally works and how it goes awry, one must consider the various ion channels involved as well as the other regulated properties impacted by adjusting those channels when regulating excitability. This raises issues of degeneracy and pleiotropy. Degeneracy refers to disparate solutions conveying equivalent function (e.g., different channel combinations yielding equivalent excitability). This many-to-one mapping contrasts the one-to-many mapping described by pleiotropy (e.g., one channel affecting multiple properties). Degeneracy facilitates homeostatic regulation by enabling a disturbance to be offset by compensatory changes in any one of several different channels or combinations thereof. Pleiotropy complicates homeostatic regulation because compensatory changes intended to regulate one property may inadvertently disrupt other properties. Co-regulating multiple properties by adjusting pleiotropic channels requires greater degeneracy than regulating one property in isolation and, by extension, can fail for additional reasons such as solutions for each property being incompatible with one another. Problems also arise if a perturbation is too strong and/or negative feedback is too weak, or because the set point is disturbed. Delineating feedback loops and their interactions provides valuable insight into how homeostatic regulation might fail. Insofar as different failure modes require distinct interventions to restore homeostasis, deeper understanding of homeostatic regulation and its pathological disruption may reveal more effective treatments for chronic neurological disorders like neuropathic pain and epilepsy. |
| first_indexed | 2024-03-13T07:56:08Z |
| format | Article |
| id | doaj.art-681e9a113b8d44a592a9a48143e362b2 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-03-13T07:56:08Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-681e9a113b8d44a592a9a48143e362b22023-06-02T05:08:38ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-06-011710.3389/fncel.2023.11845631184563Homeostatic regulation of neuronal function: importance of degeneracy and pleiotropyJane Yang0Jane Yang1Steven A. Prescott2Steven A. Prescott3Steven A. Prescott4Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, CanadaInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, CanadaNeurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, CanadaInstitute of Biomedical Engineering, University of Toronto, Toronto, ON, CanadaDepartment of Physiology, University of Toronto, Toronto, ON, CanadaNeurons maintain their average firing rate and other properties within narrow bounds despite changing conditions. This homeostatic regulation is achieved using negative feedback to adjust ion channel expression levels. To understand how homeostatic regulation of excitability normally works and how it goes awry, one must consider the various ion channels involved as well as the other regulated properties impacted by adjusting those channels when regulating excitability. This raises issues of degeneracy and pleiotropy. Degeneracy refers to disparate solutions conveying equivalent function (e.g., different channel combinations yielding equivalent excitability). This many-to-one mapping contrasts the one-to-many mapping described by pleiotropy (e.g., one channel affecting multiple properties). Degeneracy facilitates homeostatic regulation by enabling a disturbance to be offset by compensatory changes in any one of several different channels or combinations thereof. Pleiotropy complicates homeostatic regulation because compensatory changes intended to regulate one property may inadvertently disrupt other properties. Co-regulating multiple properties by adjusting pleiotropic channels requires greater degeneracy than regulating one property in isolation and, by extension, can fail for additional reasons such as solutions for each property being incompatible with one another. Problems also arise if a perturbation is too strong and/or negative feedback is too weak, or because the set point is disturbed. Delineating feedback loops and their interactions provides valuable insight into how homeostatic regulation might fail. Insofar as different failure modes require distinct interventions to restore homeostasis, deeper understanding of homeostatic regulation and its pathological disruption may reveal more effective treatments for chronic neurological disorders like neuropathic pain and epilepsy.https://www.frontiersin.org/articles/10.3389/fncel.2023.1184563/fulldegeneracypleiotropyexcitabilityion channelshomeostatic regulationrobustness |
| spellingShingle | Jane Yang Jane Yang Steven A. Prescott Steven A. Prescott Steven A. Prescott Homeostatic regulation of neuronal function: importance of degeneracy and pleiotropy Frontiers in Cellular Neuroscience degeneracy pleiotropy excitability ion channels homeostatic regulation robustness |
| title | Homeostatic regulation of neuronal function: importance of degeneracy and pleiotropy |
| title_full | Homeostatic regulation of neuronal function: importance of degeneracy and pleiotropy |
| title_fullStr | Homeostatic regulation of neuronal function: importance of degeneracy and pleiotropy |
| title_full_unstemmed | Homeostatic regulation of neuronal function: importance of degeneracy and pleiotropy |
| title_short | Homeostatic regulation of neuronal function: importance of degeneracy and pleiotropy |
| title_sort | homeostatic regulation of neuronal function importance of degeneracy and pleiotropy |
| topic | degeneracy pleiotropy excitability ion channels homeostatic regulation robustness |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1184563/full |
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