Roles of PACAP‐Containing Retinal Ganglion Cells in Circadian Timing

Aug 31, 2006International review of cytology

Roles of light-sensitive nerve cells carrying PACAP in body clock timing

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Abstract

The neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP) is essential for light entrainment of the brain's biological clock.

The brain's biological clock located in the suprachiasmatic nucleus (SCN) generates circadian rhythms in physiology and behavior.
Light-dark cycles are the primary stimulus for adjusting the biological clock to the 24-hour day.
PACAP is found exclusively in the neural pathway that transmits light information from the eyes to the SCN.
Retinal ganglion cells in this pathway are photosensitive and play a role in regulating circadian timing and other light-dependent responses.
Research shows that PACAP and glutamate interact in a concentration-dependent manner during the light entrainment process.

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The brain's biological clock located in the suprachiasmatic nucleus (SCN) generates circadian rhythms in physiology and behavior. The clock-driven rhythms need daily adjustment (entrainment) to be synchronized with the astronomical day of 24 h. The most important stimulus for entrainment of the clock is the light-dark (LD) cycle. In this review functional elements of the light entrainment pathway will be considered with special focus on the neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP), which is found exclusively in the monosynaptic neuronal pathway mediating light information to the SCN, the retinohypothalamic tract (RHT). The retinal ganglion cells of the RHT are intrinsically photosensitive due to the expression of melanopsin and seem to constitute a non-image forming photosensitive system in the mammalian eye regulating circadian timing, masking behavior, light-regulated melatonin secretion, and the pupillary light reflex. Evidence from in vitro and in vivo studies and studies of mice lacking PACAP and the specific PACAP receptor (PAC1) indicate that PACAP and glutamate are neurotransmitters in the RHT which in a clock and concentration-dependent manner interact during light entrainment of the clock.

Roles of PACAP‐Containing Retinal Ganglion Cells in Circadian Timing

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