Abstract
BackgroundPrevious studies indicate that light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells that contain both glutamate and pituitary adenylyl cyclase activating peptide (PACAP). While the role of glutamate in this pathway has been well studied, the involvement of PACAP and its receptors are only beginning to be understood. Speculating that PACAP may function to modulate how neurons in the suprachiasmatic nucleus respond to glutamate, we used electrophysiological and calcium imaging tools to examine possible cellular interactions between these co-transmitters.ResultsExogenous 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.ConclusionThe results reported here show that PACAP is a potent modulator of glutamatergic signalling within the SCN in the early night.
Highlights
Previous studies indicate that light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells that contain both glutamate and pituitary adenylyl cyclase activating peptide (PACAP)
PACAP enhanced excitatory synaptic transmission measured in mouse SCN neurons PACAP is co-expressed with glutamate in at least some of the retinal ganglion cell population that innervates the SCN [10,11]
Whole cell patch clamp recording techniques were used to measure the sEPSCs in ventral SCN neurons during the night (ZT 15– 17)
Summary
Previous studies indicate that light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells that contain both glutamate and pituitary adenylyl cyclase activating peptide (PACAP). 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. 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]
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