Mechanisms of Sustained Increases in <i>γ</i> Power Post-Ketamine in a Computational Model of the Hippocampal CA3: Implications for Ketamine’s Antidepressant Mechanism of Action
Subanaesthetic doses of ketamine increase <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> oscillation power in neural activity measured usin...
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MDPI AG
2023-11-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/11/1562 |
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| author | Maximilian Petzi Selena Singh Thomas Trappenberg Abraham Nunes |
| author_facet | Maximilian Petzi Selena Singh Thomas Trappenberg Abraham Nunes |
| author_sort | Maximilian Petzi |
| collection | DOAJ |
| description | Subanaesthetic doses of ketamine increase <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> oscillation power in neural activity measured using electroencephalography (EEG), and this effect lasts several hours after ketamine administration. The mechanisms underlying this effect are unknown. Using a computational model of the hippocampal cornu ammonis 3 (CA3) network, which is known to reproduce ketamine’s acute effects on <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> power, we simulated the plasticity of glutamatergic synapses in pyramidal cells to test which of the following hypotheses would best explain this sustained <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> power: <i>the direct inhibition hypothesis</i>, which proposes that increased <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> power post-ketamine administration may be caused by the potentiation of recurrent collateral synapses, and <i>the disinhibition hypothesis</i>, which proposes that potentiation affects synapses from both recurrent and external inputs. Our results suggest that the strengthening of external connections to pyramidal cells is able to account for the sustained <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> power increase observed post-ketamine by increasing the overall activity of and synchrony between pyramidal cells. The strengthening of recurrent pyramidal weights, however, would cause an additional phase shifted voltage increase that ultimately reduces <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> power due to partial cancellation. Our results therefore favor the disinhibition hypothesis for explaining sustained <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> oscillations after ketamine administration. |
| first_indexed | 2024-03-09T16:58:23Z |
| format | Article |
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| language | English |
| last_indexed | 2024-03-09T16:58:23Z |
| publishDate | 2023-11-01 |
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| spelling | doaj.art-2bfa5e8903d44c5a8131d6337d67a16f2023-11-24T14:32:44ZengMDPI AGBrain Sciences2076-34252023-11-011311156210.3390/brainsci13111562Mechanisms of Sustained Increases in <i>γ</i> Power Post-Ketamine in a Computational Model of the Hippocampal CA3: Implications for Ketamine’s Antidepressant Mechanism of ActionMaximilian Petzi0Selena Singh1Thomas Trappenberg2Abraham Nunes3Faculty of Computer Science, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, ON L8S 4L6, CanadaFaculty of Computer Science, Dalhousie University, Halifax, NS B3H 4R2, CanadaFaculty of Computer Science, Dalhousie University, Halifax, NS B3H 4R2, CanadaSubanaesthetic doses of ketamine increase <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> oscillation power in neural activity measured using electroencephalography (EEG), and this effect lasts several hours after ketamine administration. The mechanisms underlying this effect are unknown. Using a computational model of the hippocampal cornu ammonis 3 (CA3) network, which is known to reproduce ketamine’s acute effects on <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> power, we simulated the plasticity of glutamatergic synapses in pyramidal cells to test which of the following hypotheses would best explain this sustained <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> power: <i>the direct inhibition hypothesis</i>, which proposes that increased <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> power post-ketamine administration may be caused by the potentiation of recurrent collateral synapses, and <i>the disinhibition hypothesis</i>, which proposes that potentiation affects synapses from both recurrent and external inputs. Our results suggest that the strengthening of external connections to pyramidal cells is able to account for the sustained <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> power increase observed post-ketamine by increasing the overall activity of and synchrony between pyramidal cells. The strengthening of recurrent pyramidal weights, however, would cause an additional phase shifted voltage increase that ultimately reduces <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> power due to partial cancellation. Our results therefore favor the disinhibition hypothesis for explaining sustained <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>γ</mi></semantics></math></inline-formula> oscillations after ketamine administration.https://www.mdpi.com/2076-3425/13/11/1562ketaminecomputational modelneurondepressionhippocampusCA3 |
| spellingShingle | Maximilian Petzi Selena Singh Thomas Trappenberg Abraham Nunes Mechanisms of Sustained Increases in <i>γ</i> Power Post-Ketamine in a Computational Model of the Hippocampal CA3: Implications for Ketamine’s Antidepressant Mechanism of Action Brain Sciences ketamine computational model neuron depression hippocampus CA3 |
| title | Mechanisms of Sustained Increases in <i>γ</i> Power Post-Ketamine in a Computational Model of the Hippocampal CA3: Implications for Ketamine’s Antidepressant Mechanism of Action |
| title_full | Mechanisms of Sustained Increases in <i>γ</i> Power Post-Ketamine in a Computational Model of the Hippocampal CA3: Implications for Ketamine’s Antidepressant Mechanism of Action |
| title_fullStr | Mechanisms of Sustained Increases in <i>γ</i> Power Post-Ketamine in a Computational Model of the Hippocampal CA3: Implications for Ketamine’s Antidepressant Mechanism of Action |
| title_full_unstemmed | Mechanisms of Sustained Increases in <i>γ</i> Power Post-Ketamine in a Computational Model of the Hippocampal CA3: Implications for Ketamine’s Antidepressant Mechanism of Action |
| title_short | Mechanisms of Sustained Increases in <i>γ</i> Power Post-Ketamine in a Computational Model of the Hippocampal CA3: Implications for Ketamine’s Antidepressant Mechanism of Action |
| title_sort | mechanisms of sustained increases in i γ i power post ketamine in a computational model of the hippocampal ca3 implications for ketamine s antidepressant mechanism of action |
| topic | ketamine computational model neuron depression hippocampus CA3 |
| url | https://www.mdpi.com/2076-3425/13/11/1562 |
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