Regulation of glutamatergic signalling by PACAP in the mammalian suprachiasmatic nucleus

Exogenous application of PACAP increased both the amplitude and frequency of spontaneous excitatory postsynaptic currents recorded from SCN neurons in a mouse brain slice preparation. PACAP also increased the magnitude of AMPA-evoked currents through a mechanism mediated by PAC1 receptors and the adenylyl cyclase-signalling cascade. This enhancement of excitatory currents was not limited to those evoked by AMPA as the magnitude of NMDA currents were also enhanced by application of PACAP. Furthermore, PACAP enhanced AMPA and NMDA evoked calcium transients while PACAP alone produced very little change in resting calcium in most mouse SCN neurons. Finally, in rat SCN neurons, exogenous PACAP enhanced AMPA evoked currents and calcium transients as well evoked robust calcium transients on its own.The results reported here show that PACAP is a potent modulator of glutamatergic signalling within the SCN in the early night.In mammals, the neural structure responsible for most circadian behaviours can be localized to a bilaterally paired structure in the hypothalamus, the suprachiasmatic nucleus (SCN). These SCN neurons must be synchronized to each other as well as to the environment in order to function adaptively. The daily cycle of light and dark is the dominant environmental cue responsible for synchronizing this biological timing system to the environment. The SCN receives photic information directly through a monosynaptic projection from the retina known as the retinal hypothalamic tract (RHT). The RHT comprises a distinct subset of retinal ganglion cells that contain a novel photopigment melanopsin and are directly light-sensitive [1,2]. There is a variety of evidence that the amino acid glutamate is a transmitter at the RHT/SCN synaptic connection and that this transmitter plays a critical role in mediating photic regulation of the circadian system [3,4]. One of the main post -synaptic consequences of glutamate receptor activation within the SCN is an increase in int