Which structure do intrinsically photosensitive retinal ganglion cells (ipRGCs) predominantly synapse on to transmit visual information about the light/dark cycle?

Suprachiasmatic Nucleus (SCN)

Intrinsically photosensitive retinal ganglion cells (ipRGCs) predominantly synapse directly on the suprachiasmatic nucleus (SCN) to transmit visual information about the light/dark cycle. 1

Anatomical Pathway

The retinohypothalamic tract is the neural pathway through which ipRGCs convey light information to regulate circadian rhythms:

• ipRGCs serve as the primary conduit for light information reaching the SCN, forming the retinohypothalamic tract that directly innervates this hypothalamic structure 1

• The SCN functions as the master circadian pacemaker that receives direct input from melanopsin-expressing ipRGCs to entrain circadian rhythms to environmental light-dark cycles 1, 2

• This circuit is modulated by rod and cone inputs within the retina, but ipRGCs themselves are intrinsically photosensitive and can respond to light even when all synaptic input from rods and cones is blocked 3

Functional Significance

The ipRGC-SCN connection is essential for circadian photoentrainment:

• Glutamate is the principal neurotransmitter of the retinohypothalamic projection from ipRGCs to the SCN, and glutamate transmission from ipRGCs is necessary for normal light entrainment at moderate light levels 4

• The SCN uses diffusible, systemic signals to coordinate the timing of circadian clocks in other brain regions and throughout the body after receiving light input from ipRGCs 1

• Changes in ambient light sensed by ipRGCs entrain the SCN clock to new lighting conditions, with the SCN being highly responsive to changes in environmental light-dark cycles compared to peripheral organs 1

Other ipRGC Targets

While the SCN is the predominant target for circadian regulation, ipRGCs also project to other brain regions:

• ipRGCs project to the olivary pretectal nucleus (OPN) to mediate the pupillary light response 5

• ipRGCs send projections to brain regions corresponding to sleep, cognition, and pupil control, though the SCN remains the primary target for circadian rhythm regulation 1

The other answer choices are incorrect: the paraventricular nucleus, tuberomammillary nucleus, and ventrolateral preoptic area receive indirect circadian signals downstream from the SCN rather than direct ipRGC input, and the pineal gland is regulated by the SCN but does not receive direct retinal input 1.