Modulation of cortical slow oscillatory rhythm by GABAB receptors: an in vitro experimental and computational study
| Autor: | Jesus Manrique, Néstor Parga, Ramon Reig, Daniel Jercog, Maria Perez-Zabalza, Maria V. Sanchez-Vives, Milena Winograd |
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| Přispěvatelé: | European Commission, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Generalitat de Catalunya |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Physiology Chemistry GABAB receptor 3. Good health Blockade 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Rhythm nervous system Cerebral cortex Modulation (music) medicine Excitatory postsynaptic potential Receptor Neuroscience 030217 neurology & neurosurgery Slow-wave sleep |
| Zdroj: | The Journal of Physiology Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Slow wave oscillations (SWOs) dominate cortical activity during deep sleep, anaesthesia and in some brain lesions. SWOs are composed of periods of activity (Up states) interspersed with periods of silence (Down states). The rhythmicity expressed during SWOs integrates neuronal and connectivity properties of the network and is often altered under pathological conditions. Adaptation mechanisms as well as synaptic inhibition mediated by GABAB receptors (GABAB‐Rs) have been proposed as mechanisms governing the termination of Up states. The interplay between these two mechanisms is not well understood, and the role of GABAB‐Rs controlling the whole cycle of the SWO has not been described. Here we contribute to its understanding by combining in vitro experiments on spontaneously active cortical slices and computational techniques. GABAB‐R blockade modified the whole SWO cycle, not only elongating Up states, but also affecting the subsequent Down state duration. Furthermore, while adaptation tends to yield a rather regular behaviour, we demonstrate that GABAB‐R activation desynchronizes the SWOs. Interestingly, variability changes could be accomplished in two different ways: by either shortening or lengthening the duration of Down states. Even when the most common observation following GABAB‐Rs blocking is the lengthening of Down states, both changes are expressed experimentally and also in numerical simulations. Our simulations suggest that the sluggishness of GABAB‐Rs to follow the excitatory fluctuations of the cortical network can explain these different network dynamics modulated by GABAB‐Rs. This work was supported by EU H2020 Research and Innovation Programme Grant 945539 (HBP SGA3), BFU2017‐85048‐R (MINECO) and Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya ‐AGAUR‐ (IU16‐011508) to MVSV and PGC2018‐101992‐B‐100 (MINECO) to NP. |
| Databáze: | OpenAIRE |
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