Immediate responses to ambient light in vivo reveal distinct subpopulations of suprachiasmatic VIP neurons

Vasoactive intestinal peptide excites GnRH neurons via KCa3.1, a potential player in the slow afterhyperpolarization current

“…Vasoactive intestinal peptide (VIP) is an important component of the SCN which relays circadian information to neuronal populations, including GnRH neurons. VIP signaling is involved in the generation and/or timing of the GnRH/LH surge in females ( Harney et al, 1996 ; Kahan et al, 2023 ), and reproductive behavior in males ( Kukino et al, 2022 ). However, little is known about the signaling pathway activated downstream of the VIP receptor in GnRH neurons ( Christian and Moenter, 2008 ; Piet et al, 2016 ).…”

“…Vasoactive intestinal peptide neurons within the SCN project to GnRH neurons in both male and female animals [rodents: ( Beek et al, 1994 ; Van der Beek et al, 1997 ; Horvath et al, 1998 ); non-human primates: ( Abizaid et al, 2004 )]. In vivo studies support a role for VIP signaling in the generation and/or timing of the GnRH/LH surge in females, with infusion of VIP antisense into the SCN or specific ablation of SCN VIP neurons attenuating the steroid-induced LH surge ( Harney et al, 1996 ; Kahan et al, 2023 ), and reproductive behavior in males ( Kukino et al, 2022 ). In vitro , VIP stimulates GnRH release ( Samson et al, 1981 ) and in ex vivo preparations, VIP increases GnRH cell firing rate in both male and female mice ( Piet et al, 2016 ), though the response is time-of-the-day and estradiol (E2)-dependent in females to optimize the pre-ovulatory surge ( Christian and Moenter, 2008 ).…”

“…In adult female rodents, about 30–40% of GnRH neurons are contacted by VIP fibers ( Beek et al, 1993 ; Horvath et al, 1998 ), and ∼40% express the VIP receptor, VPAC2 (aka VIP2), which did not change between morning and afternoon of proestrus ( Smith et al, 2000 ). However, a recent study showed that specific suppression of VPAC2 expression in GnRH neurons alters female mice estrous cycles ( Kahan et al, 2023 ). Functionally, GnRH neurons in females contacted by VIP preferentially expressed c-fos at the time of the GnRH/LH surge ( Beek et al, 1994 ) and infusion of VIP antisense in SCN impairs c-fos expression in these GnRH neurons ( Gerhold et al, 2005 ; Kahan et al, 2023 ).…”

“…However, a recent study showed that specific suppression of VPAC2 expression in GnRH neurons alters female mice estrous cycles ( Kahan et al, 2023 ). Functionally, GnRH neurons in females contacted by VIP preferentially expressed c-fos at the time of the GnRH/LH surge ( Beek et al, 1994 ) and infusion of VIP antisense in SCN impairs c-fos expression in these GnRH neurons ( Gerhold et al, 2005 ; Kahan et al, 2023 ). In addition, a recent study showed that the loss of the VAX1 transcription factor required for normal VIP expression, delays puberty onset, alters females estrous cycle length and potentiates the GnRH response to kisspeptin stimulation ( Van Loh et al, 2023 ).…”

Cell-type specific circadian transcription factor BMAL1 roles in excitotoxic hippocampal lesions to enhance neurogenesis

“… 10 Ganglion cells receive photic information and convey it to the circadian pacemaker suprachiasmatic nucleus (SCN) in the hypothalamus by releasing neurotransmitter glutamate and neuromodulator pituitary adenylyl cyclase-activating peptide (PACAP). 11 , 12 , 13 Glutamate acts at N-methyl-D-aspartate (NMDA) receptors on SCN neurons and phosphorylates a transcription factor cAMP-responsive element-binding protein (CREB). 14 , 15 Phosphorylated CREB (pCREB) transcribes Per1 and Per2 in BMAL1-independent ways, but PER1 and PER2 expressed by pCREB can repress BMAL1/CLOCK to incorporate photic information into SCN clocks.…”