Sleep and Serotonin Modulate Paracapsular Nitric Oxide Synthase Expressing Neurons of the Amygdala.
Unraveling the roles of distinct neuron types is a fundamental challenge to understanding brain function in health and disease. In the amygdala, a brain structure regulating emotional behavior, the diversity of GABAergic neurons has been only partially explored. We report a novel population of GABAergic amygdala neurons expressing high levels of neuronal nitric oxide synthase (nNOS). These cells are predominantly localized along basolateral amygdala (BLA) boundaries. Performingex vivopatch-clamp recordings from nNOS+neurons in Nos1-CreER;Ai9 mice, we observed that nNOS+neurons located along the external capsule display distinctive electrophysiological properties, axonal and dendritic arborization, and connectivity. Examining their c-Fos expression, we found that paracapsular nNOS+neurons are activated during a period of undisturbed sleep following sleep deprivation, but not during sleep deprivation. Consistently, we found that dorsal raphe serotonin [5-hydroxytryptamine (5-HT)] neurons, which are involved in sleep-wake regulation, innervate nNOS+neurons. Bath application of 5-HT hyperpolarizes nNOS+neurons via 5-HT1A receptors. This hyperpolarization produces a reduction in firing rate and, occasionally, a switch from tonic to burst firing mode, thereby contrasting with the classic depolarizing effect of 5-HT on BLA GABAergic cells reported so far. Thus, nNOS+cells are a distinct cell type of the amygdala that controls the activity of downstream neurons in both amygdaloid and extra-amygdaloid regions in a vigilance state-dependent fashion. Given the strong links among mood, sleep deprivation, and 5-HT, the recruitment of paracapsular nNOS+neurons following high sleep pressure may represent an important mechanism in emotional regulation.
MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3TH, UK; Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
Marco
0000-0002-7005-3453
M
Bocchio
Department of Physiology, Anatomy and Genetics, University of Oxford , Oxford OX1 3PT, UK.
Simon P
SP
Fisher
MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3TH, UK; Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
Gunes
0000-0003-3013-0271
G
Unal
MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3TH, UK; Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
Tommas J
TJ
Ellender
Department of Physiology, Anatomy and Genetics, University of Oxford , Oxford OX1 3PT, UK.
Vladyslav V
VV
Vyazovskiy
MRC Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3TH, UK; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark; The Danish Research Institute of Translational Neuroscience (DANDRITE), Nordic EMBL Partnership for Molecular Medicine, Aarhus University, 8000 Aarhus C, Denmark.
Marco
0000-0002-2742-5485
M
Capogna
D000679:Amygdala / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D065847:Dorsal Raphe Nucleus / Q000166:cytology / Q000378:metabolism; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000378:metabolism; D046509:Tissue Culture Techniques
D016760:Proto-Oncogene Proteins c-fos; D012701:Serotonin; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse
amygdala; electrophysiology; interneuron; nitric oxide; serotonin; sleep 