Interleukin-1 inhibits firing of serotonergic neurons in the dorsal raphe nucleus and enhances GABAergic inhibitory post-synaptic potentials.
In vitro electrophysiological data suggest that interleukin-1 may promote non-rapid eye movement sleep by inhibiting spontaneous firing of wake-active serotonergic neurons in the dorsal raphe nucleus (DRN). Interleukin-1 enhances GABA inhibitory effects. DRN neurons are under an inhibitory GABAergic control. This study aimed to test the hypothesis that interleukin-1 inhibits DRN serotonergic neurons by potentiating GABAergic inhibitory effects. In vitro intracellular recordings were performed to assess the responses of physiologically and pharmacologically identified DRN serotonergic neurons to rat recombinant interleukin-1beta. Coronal slices containing DRN were obtained from male Sprague-Dawley rats. The impact of interleukin-1 on firing rate and on evoked post-synaptic potentials was determined. Evoked post-synaptic potentials were induced by stimulation with a bipolar electrode placed on the surface of the slice ventrolateral to DRN. Addition of interleukin-1 (25 ng/mL) to the bath perfusate significantly decreased firing rates of DRN serotonergic neurons from 1.3 +/- 0.2 Hz (before administration) to 0.7 +/- 0.2 Hz. Electrical stimulation induced depolarizing evoked post-synaptic potentials in DRN serotonergic neurons. The application of glutamatergic and GABAergic antagonists unmasked two different post-synaptic potential components: a GABAergic evoked inhibitory post-synaptic potentials and a glutamatergic evoked excitatory post-synaptic potentials, respectively. Interleukin-1 increased GABAergic evoked inhibitory post-synaptic potentials amplitudes by 30.3 +/- 3.8% (n = 6) without affecting glutamatergic evoked excitatory post-synaptic potentials. These results support the hypothesis that interleukin-1 inhibitory effects on DRN serotonergic neurons are mediated by an interleukin-1-induced potentiation of evoked GABAergic inhibitory responses.
Brambilla
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Institute of Human Physiology II, Guiseppe Moruzzi Center for Experimental Sleep Research, University of Milan Medical School, Via Mangiagalli, 32, 20133 Milano, Italy. dario.brambilla@unimi.it
Franciosi
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Imeri
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D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D011903:Raphe Nuclei / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007375:Interleukin-1; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline