Abstract
The median preoptic nucleus (MnPO) and the ventrolateral preoptic nucleus (VLPO) are two brain structures that contain neurons essential for promoting non-rapid eye movement (NREM) sleep. However, their connections are still largely unknown. Here, we describe for the first time a slice preparation with an oblique coronal slicing angle at 70° from the horizontal in which their connectivity is preserved. Using the in vivo iDISCO method following viral infection of the MnPO or ex vivo biocytin crystal deposition in the MnPO of mouse brain slices, we revealed a strong axonal pathway from the MnPO to the VLPO. Then, to further explore the functionality of these projections, acute 70° slices were placed on multielectrode arrays (MEAs) and electrical stimulations were performed near the MnPO. Recordings of the signals propagation throughout the slices revealed a preferential pathway from the MnPO to the VLPO. Finally, we performed an input–output curve of field responses evoked by stimulation of the MnPO and recorded in the VLPO. We found that field responses were inhibited by GABAA receptor antagonist, suggesting that afferent inputs from the MnPO activate VLPO neuronal networks by disinhibition.
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References
Abbott SBG, Saper CB (2017) Median preoptic glutamatergic neurons promote thermoregulatory heat loss and water consumption in mice. J Physiol 595:6569–6583. https://doi.org/10.1113/JP274667
Abbott SBG, Machado NLS, Geerling JC, Saper CB (2016) Reciprocal control of drinking behavior by median preoptic neurons in mice. J Neurosci 36:8228–8237. https://doi.org/10.1523/jneurosci.1244-16.2016
Alam MA, Kumar S, McGinty D et al (2014) Neuronal activity in the preoptic hypothalamus during sleep deprivation and recovery sleep. J Neurophysiol 111:287–299. https://doi.org/10.1152/jn.00504.2013
Anaclet C, Ferrari L, Arrigoni E et al (2014) The GABAergic parafacial zone is a medullary slow wave sleep-promoting center. Nat Neurosci 17:1217–1224. https://doi.org/10.1038/nn.3789
Chever O, Dossi E, Pannasch U et al (2016) Astroglial networks promote neuronal coordination. Sci Signal 9:1–9. https://doi.org/10.1126/scisignal.aad3066
Chou TC, Bjorkum AA, Gaus SE et al (2002) Afferents to the ventrolateral preoptic nucleus. J Neurosci 22:977–990
Economo CV (1930) Sleep as a problem of localization. J Nerv Ment Dis 71:249–259. https://doi.org/10.1097/00005053-193003000-00001
Franklin KBJ, Paxinos G (2007) The mouse brain in stereotaxic coordinates, 3rd edn. Academic Press, San Diego
Gaus SE, Strecker RE, Tate BA et al (2002) Ventrolateral preoptic nucleus contains sleep-active, galaninergic neurons in multiple mammalian species. Neuroscience 115:285–294
Gong S, Zheng C, Doughty ML et al (2003) A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425:917–925. https://doi.org/10.1038/nature02033
Gong H, McGinty D, Guzman-Marin R et al (2004) Activation of c-Fos in GABAergic neurones in the preoptic area during sleep and in response to sleep deprivation. J Physiol 556:935–946
Gvilia I, Xu F, McGinty D, Szymusiak R (2006) Homeostatic regulation of sleep: a role for preoptic area neurons. J Neurosci 26:9426–9433. https://doi.org/10.1523/JNEUROSCI.2012-06.2006
Kroeger D, Absi G, Gagliardi C et al (2018) Galanin neurons in the ventrolateral preoptic area promote sleep and heat loss in mice. Nat Commun. https://doi.org/10.1038/s41467-018-06590-7
MacLean JN, Fenstermaker V, Watson BO, Yuste R (2006) A visual thalamocortical slice. Nat Methods 3:129–134. https://doi.org/10.1038/nmeth849
McKinley MJ, Yao ST, Uschakov A et al (2015) The median preoptic nucleus: front and centre for the regulation of body fluid, sodium, temperature, sleep and cardiovascular homeostasis. Acta Physiol (Oxf) 214:8–32. https://doi.org/10.1111/apha.12487
Pannasch U, Freche D, Dallérac G et al (2014) Connexin 30 sets synaptic strength by controlling astroglial synapse invasion. Nat Neurosci 17:549–558. https://doi.org/10.1038/nn.3662
Renier N, Wu Z, Simon DJ et al (2014) IDISCO: a simple, rapid method to immunolabel large tissue samples for volume imaging. Cell 159:896–910. https://doi.org/10.1016/j.cell.2014.10.010
Ross FM, Cassidy J, Wilson M, Davies SN (2000) Developmental regulation of hippocampal excitatory synaptic transmission by metabotropic glutamate receptors. Br J Pharmacol 131:453–464. https://doi.org/10.1038/sj.bjp.0703610
Sakai K, Crochet S (2001) Differentiation of presumed serotonergic dorsal raphe neurons in relation to behavior and wake–sleep states. Neuroscience 104:1141–1155
Saper CB, Scammell TE, Lu J (2005) Hypothalamic regulation of sleep and circadian rhythms. Nature 437:1257–1263
Saper CB, Fuller PM, Pedersen NP et al (2010) Sleep state switching. Neuron 68:1023–1042
Scammell TE, Arrigoni E, Lipton JO (2017) Neural circuitry of wakefulness and sleep. Neuron 93:747–765. https://doi.org/10.1016/j.neuron.2017.01.014
Scharbarg E, Daenens M, Lemaître F et al (2016) Astrocyte-derived adenosine is central to the hypnogenic effect of glucose. Sci Rep 6:19107
Sherin JE, Shiromani PJ, McCarley RW, Saper CB (1996) Activation of ventrolateral preoptic neurons during sleep. Science 271:216–219
Sherin JE, Elmquist JK, Torrealba F, Saper CB (1998) Innervation of histaminergic tuberomammillary neurons by GABAergic and galaninergic neurons in the ventrolateral preoptic nucleus of the rat. J Neurosci 18:4705–4721
Suntsova N, Szymusiak R, Alam MN et al (2002) Sleep-waking discharge patterns of median preoptic nucleus neurons in rats. J Physiol 543:665–677. https://doi.org/10.1113/jphysiol.2002.023085
Szymusiak R, Alam N, Steininger TL, McGinty D (1998) Sleep-waking discharge patterns of ventrolateral preoptic/anterior hypothalamic neurons in rats. Brain Res 803:178–188
Takahashi K, Lin J-S, Sakai K (2009) Characterization and mapping of sleep-waking specific neurons in the basal forebrain and preoptic hypothalamus in mice. Neuroscience 161:269–292. https://doi.org/10.1016/j.neuroscience.2009.02.075
Thompson RH, Swanson LW (2003) Structural characterization of a hypothalamic visceromotor pattern generator network. Brain Res Brain Res Rev 41:153–202
Uschakov A, Gong H, McGinty D, Szymusiak R (2006) Sleep-active neurons in the preoptic area project to the hypothalamic paraventricular nucleus and perifornical lateral hypothalamus. Eur J Neurosci 23:3284–3296
Uschakov A, Gong H, McGinty D, Szymusiak R (2007) Efferent projections from the median preoptic nucleus to sleep- and arousal-regulatory nuclei in the rat brain. Neuroscience 150:104–120
Williams RH, Chee MJS, Kroeger D et al (2014) Optogenetic-mediated release of histamine reveals distal and autoregulatory mechanisms for controlling arousal. J Neurosci 34:6023–6029. https://doi.org/10.1523/JNEUROSCI.4838-13.2014
Zhang W, Zhou Q, Chen W et al (2017) A hypothalamic circuit that controls body temperature. Proc Natl Acad Sci 114:E1755. https://doi.org/10.1073/pnas.1701881114
Acknowledgements
This work was supported by grants from the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé et de la Recherche Médicale (Inserm), Collège de France and the Marie Sklodowska-Curie Research and Innovation Programme EU-GliaPhD (722053) (N.R.). We thank all the members of the animal house facility and imaging platform from Collège de France, including Philippe Mailly in particular. We gratefully acknowledge Yves Dupraz for the design of the brain cutting angles and IT people including Aurélien Agneray, in particular, for excellent and prompt technical assistance.
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All animal procedures were carried out according to the guidelines of European Community Council Directives of January first 2013 (2010/63/EU) and followed our local guidelines for the ethical treatment of animal care [Center for Interdisciplinary Research in Biology in College de France (France)]. The number of animals in our study was kept to the necessary minimum.
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Walter, A., van der Spek, L., Hardy, E. et al. Structural and functional connections between the median and the ventrolateral preoptic nucleus. Brain Struct Funct 224, 3045–3057 (2019). https://doi.org/10.1007/s00429-019-01935-4
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DOI: https://doi.org/10.1007/s00429-019-01935-4