Control of sleep-to-wake transitions via fast amino acid and slow neuropeptide transmission
The locus coeruleus (LC) modulates cortical, subcortical, cerebellar, brainstem and spinal cord circuits and it expresses receptors for neuromodulators that operate on a time scale of several seconds. Evidence from anatomical, electrophysiological and optogenetic experiments has shown that LC neuron...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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IOP Publishing
2014-01-01
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| Series: | New Journal of Physics |
| Subjects: | |
| Online Access: | https://doi.org/10.1088/1367-2630/16/11/115010 |
| _version_ | 1797751542166585344 |
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| author | Thiago Mosqueiro Luis de Lecea Ramon Huerta |
| author_facet | Thiago Mosqueiro Luis de Lecea Ramon Huerta |
| author_sort | Thiago Mosqueiro |
| collection | DOAJ |
| description | The locus coeruleus (LC) modulates cortical, subcortical, cerebellar, brainstem and spinal cord circuits and it expresses receptors for neuromodulators that operate on a time scale of several seconds. Evidence from anatomical, electrophysiological and optogenetic experiments has shown that LC neurons receive input from a group of neurons called hypocretin neurons that release a neuropeptide called hypocretin. It is less well known how these two groups of neurons can be coregulated using GABAergic (GABA standing for gamma aminobutyric acid) neurons. As the time scale for GABA _A inhibition is several orders of magnitude faster than that for the hypocretin neuropeptide effect, we investigate the limits of circuit activity regulation using a realistic model of neurons. Our investigation shows that GABA _A inhibition is insufficient to control the activity levels of the LCs. Although slower forms of GABA _A can in principle work, there is not much plausibility due to the low probability of the presence of slow GABA _A and lack of robust stability at the maximum firing frequencies. The best possible control mechanism predicted by our modeling analysis is the presence of inhibitory neuropeptides, which exert effects on a similar time scale to the hypocretin/orexin. Although the nature of these inhibitory neuropeptides has not been identified yet, it provides the most efficient mechanism in the modeling analysis. Finally, we present a reduced mean-field model that perfectly captures the dynamics and the phenomena generated by this circuit. This investigation shows that brain communication involving multiple time scales can be better controlled by employing orthogonal mechanisms of neural transmission to decrease interference between cognitive processes and hypothalamic functions. |
| first_indexed | 2024-03-12T16:50:02Z |
| format | Article |
| id | doaj.art-de68868533614f7c80941af25ba2e801 |
| institution | Directory Open Access Journal |
| issn | 1367-2630 |
| language | English |
| last_indexed | 2024-03-12T16:50:02Z |
| publishDate | 2014-01-01 |
| publisher | IOP Publishing |
| record_format | Article |
| series | New Journal of Physics |
| spelling | doaj.art-de68868533614f7c80941af25ba2e8012023-08-08T11:23:36ZengIOP PublishingNew Journal of Physics1367-26302014-01-01161111501010.1088/1367-2630/16/11/115010Control of sleep-to-wake transitions via fast amino acid and slow neuropeptide transmissionThiago Mosqueiro0Luis de Lecea1Ramon Huerta2Institute of Physics of São Carlos, University of São Paulo , São Carlos, SP, Brazil; BioCircuits Institute, University of California , San Diego, La Jolla, CA, USADepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine , Stanford, CA, USABioCircuits Institute, University of California , San Diego, La Jolla, CA, USAThe locus coeruleus (LC) modulates cortical, subcortical, cerebellar, brainstem and spinal cord circuits and it expresses receptors for neuromodulators that operate on a time scale of several seconds. Evidence from anatomical, electrophysiological and optogenetic experiments has shown that LC neurons receive input from a group of neurons called hypocretin neurons that release a neuropeptide called hypocretin. It is less well known how these two groups of neurons can be coregulated using GABAergic (GABA standing for gamma aminobutyric acid) neurons. As the time scale for GABA _A inhibition is several orders of magnitude faster than that for the hypocretin neuropeptide effect, we investigate the limits of circuit activity regulation using a realistic model of neurons. Our investigation shows that GABA _A inhibition is insufficient to control the activity levels of the LCs. Although slower forms of GABA _A can in principle work, there is not much plausibility due to the low probability of the presence of slow GABA _A and lack of robust stability at the maximum firing frequencies. The best possible control mechanism predicted by our modeling analysis is the presence of inhibitory neuropeptides, which exert effects on a similar time scale to the hypocretin/orexin. Although the nature of these inhibitory neuropeptides has not been identified yet, it provides the most efficient mechanism in the modeling analysis. Finally, we present a reduced mean-field model that perfectly captures the dynamics and the phenomena generated by this circuit. This investigation shows that brain communication involving multiple time scales can be better controlled by employing orthogonal mechanisms of neural transmission to decrease interference between cognitive processes and hypothalamic functions.https://doi.org/10.1088/1367-2630/16/11/115010hypothalamusHodgkin-Huxley modelsleeporexinGABAphase-resetting curves |
| spellingShingle | Thiago Mosqueiro Luis de Lecea Ramon Huerta Control of sleep-to-wake transitions via fast amino acid and slow neuropeptide transmission New Journal of Physics hypothalamus Hodgkin-Huxley model sleep orexin GABA phase-resetting curves |
| title | Control of sleep-to-wake transitions via fast amino acid and slow neuropeptide transmission |
| title_full | Control of sleep-to-wake transitions via fast amino acid and slow neuropeptide transmission |
| title_fullStr | Control of sleep-to-wake transitions via fast amino acid and slow neuropeptide transmission |
| title_full_unstemmed | Control of sleep-to-wake transitions via fast amino acid and slow neuropeptide transmission |
| title_short | Control of sleep-to-wake transitions via fast amino acid and slow neuropeptide transmission |
| title_sort | control of sleep to wake transitions via fast amino acid and slow neuropeptide transmission |
| topic | hypothalamus Hodgkin-Huxley model sleep orexin GABA phase-resetting curves |
| url | https://doi.org/10.1088/1367-2630/16/11/115010 |
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