Clock-driven vasopressin neurotransmission mediates anticipatory thirst prior to sleep.
Circadian rhythms have evolved to anticipate and adapt animals to the constraints of the earth's 24-hour light cycle. Although the molecular processes that establish periodicity in clock neurons of the suprachiasmatic nucleus (SCN) are well understood, the mechanisms by which axonal projections from the central clock drive behavioural rhythms are unknown. Here we show that the sleep period in mice (Zeitgeber time, ZT0-12) is preceded by an increase in water intake promoted entirely by the central clock, and not motivated by physiological need. Mice denied this surge experienced significant dehydration near the end of the sleep period, indicating that this water intake contributes to the maintenance of overnight hydromineral balance. Furthermore, this effect relies specifically on the activity of SCN vasopressin (VP) neurons that project to thirst neurons in the OVLT (organum vasculosum lamina terminalis), where VP is released as a neurotransmitter. SCN VP neurons become electrically active during the anticipatory period (ZT21.5-23.5), and depolarize and excite OVLT neurons through the activation of postsynaptic VP V1a receptors and downstream non-selective cation channels. Optogenetic induction of VP release before the anticipatory period (basal period; ZT19.5-21.5) excited OVLT neurons and prompted a surge in water intake. Conversely, optogenetic inhibition of VP release during the anticipatory period inhibited the firing of OVLT neurons and prevented the corresponding increase in water intake. Our findings reveal the existence of anticipatory thirst, and demonstrate this behaviour to be driven by excitatory peptidergic neurotransmission mediated by VP release from central clock neurons.
Centre for Research in Neuroscience and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal H3G 1A4, Canada.
C
C
Gizowski
Centre for Research in Neuroscience and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal H3G 1A4, Canada.
C
C
Zaelzer
Centre for Research in Neuroscience and Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal H3G 1A4, Canada.
C W
CW
Bourque
D000818:Animals; D059031:Anticipation, Psychological; D001683:Biological Clocks / Q000502:physiology*; D003681:Dehydration; D004326:Drinking / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D062308:Optogenetics; D066278:Organum Vasculosum / Q000166:cytology / Q000378:metabolism; D057907:Post-Synaptic Density / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism; D012890:Sleep / Q000502:physiology; D009435:Synaptic Transmission; D013894:Thirst / Q000502:physiology*; D014667:Vasopressins / Q000378:metabolism*; D014882:Water-Electrolyte Balance
D017483:Receptors, Vasopressin; D014667:Vasopressins
Front Syst Neurosci. 2011 Apr 13;5:18
21811444
J Biol Rhythms. 2006 Dec;21(6):458-69
17107936
Brain Res. 2001 Oct 19;916(1-2):172-91
11597605
Peptides. 1988 Jan-Feb;9(1):87-105
3362746
Physiol Rev. 1966 Jan;46(1):128-71
5323500
Am J Physiol Regul Integr Comp Physiol. 2015 Aug 15;309(4):R324-37
26017494
Cell Tissue Res. 2002 Jul;309(1):89-98
12111539
Trends Neurosci. 2005 Mar;28(3):145-51
15749168
Physiol Rev. 1998 Jul;78(3):583-686
9674690
Semin Nephrol. 2006 May;26(3):249-57
16713498
Nat Rev Neurosci. 2001 Jul;2(7):521-6
11433377
Am J Physiol Regul Integr Comp Physiol. 2011 Sep;301(3):R623-31
21677275
CNS Drug Rev. 2005 Spring;11(1):53-68
15867952
Nature. 2013 Jul 18;499(7458):295-300
23868258
Brain Res. 1978 Feb 3;141(1):89-103
624080
Am J Physiol Regul Integr Comp Physiol. 2003 Aug;285(2):R394-403
12714354
Curr Biol. 2008 Sep 9;18(17):R805-R815
18786386
J Biol Rhythms. 1988 Spring;3(1):1-22
2979628
Cell Rep. 2015 Oct 6;13(1):23-30
26387947
Prog Brain Res. 2002;139:197-210
12436936
Physiol Behav. 1982 Jan;28(1):139-47
7200613
J Neuroimmunol. 2003 Feb;135(1-2):72-81
12576226
Nat Methods. 2012 Jun 28;9(7):676-82
22743772
J Neurosci Methods. 2003 Sep 30;128(1-2):67-77
12948549
Annu Rev Neurosci. 2012;35:445-62
22483041
Nat Rev Neurosci. 2008 Jul;9(7):519-31
18509340
Physiol Behav. 1983 Mar;30(3):451-62
6683413
Am J Physiol. 1978 Mar;234(3):R122-9
629368
Am J Physiol Regul Integr Comp Physiol. 2008 Apr;294(4):R1390-401
18234743
Prog Brain Res. 1983;60:91-8
6665160
Am J Physiol. 1995 Sep;269(3 Pt 2):R557-64
7573556
J Neurosci. 1988 Nov;8(11):3967-77
3183709
Nat Neurosci. 2010 Mar;13(3):387-92
20081849