Welcome back. In this tutorial, I'd like to talk to you briefly about the circuitry that's responsible for the pupillary light reflex. again, our journey into the visual system is an attempt to make it a bit more simple, some of the most complex pathways and function of the brain itself. We will once again consider circuitry, that is genetically determined and provides a foundation for one very useful aspect of nervous system function. One that is exploited from a clinical point of view to assess the integrity of cranial nerves and brain stem circuits, that is the pupillary light reflex. So my learning objectives for you, are to describe the distribution of retinal axons, from ganglion cells to their major processing centers in the forebrain in the brainstem. And we have some particular brain stem targets in mind in this tutorial. And I want you to be able to use that knowledge to discuss the neuroanatomical basic for the pupillary light reflex. So let's consider again, the distribution of the axons of our retinal gangling cells. Those that reside on the temporal side of the retina, grow their axons out through the optic nerve, and they remain on the ipsilateral side of optic chiasm, being distributed to the appropriate targets in the diencephalon and to the mid-brain. those axons that arise from nasal retinal ganglion cells, that sit here in this location, close to the nose on what we call the nasal side of the retina. They grow their axons through the optic nerve. And when they get into the optic chiasm, now these axons cross the midline. And they give rise to projections to a variety of targets in the diencephalon and in the midbrain. including the hypothalamus, and the lateral geniculate nucleus of the diencephalon. And the superior colliculus and the pretectum and the midbrain. And for this discussion today, the projection of interest is this projection to the pretectum, that I would highlight here from the retina into a set of nuclei that sit in a transitional region between the diencephalon and the midbrain. And in that region of the dorsal part of the midbrain, we have the superior and inferior colliculi. That, collectively, is called the tectum. Tectum means roof. It's the roof over the cerebral aqueduct. So the region just in front of the roof is the area of our focus in this session. That's what we call the pretectum. That's where we find a collection of nuclei that receive direct input from the retina. And it's those cells that will coordinate the distribution of that sensory information to the motor structures that result in the constriction of the pupils. So let's look now at a view just specifically of this reflex circuitry. So now what we see are the sensory and the motor limbs of this reflex arc. And let's first consider the sensory limb. Now the retinas are projecting into the pretectum. And notice that the pretectum in one side of the mid line is getting input derived from both retinas. So the temporal retina of one eye, the nasal retina of the other, are both contributing input into that pretectum. So that's important. so you need to understand that the sensory signals going into one side of that circuitry are derived from both eyes. Now, the motor limb of this reflex circuitry arises out of the pretectum. Now notice another very important fact about this circuitry here, that pertains to sidedness. The projections from these pretectum nuclei to the motor nuclei in question are bilateral. So here is our pretectal nucleus and it gives rise to axons that are directed to both sides of the midline. And specifically the target there is a small parasympathetic preganglionic nucleus called the Edinger-Westphal nucleus. It sits just dorsal and slightly lateral to our somatic motor nucleus or ocular motor nucleus and it's in this Edinger-Westphal nucleus that we have the preganglionic neurons that grow axons out through the third cranial nerve. So, here in green is a Edinger-Westphal nucleus, and it's growing an axon out through the third nerve, which makes a synapse on a post-ganglionic neuron, in the ciliary ganglion. And then that neuron grows its axons, into the eye itself, to supply ganglionic parasympathetic innervation of the constrictor muscle of the iris. So, when this motor signal is conveyed down that third nerve, the iris will constrict. Now, notice one other important fact that's worth emphasizing about the organization of the motor limb of this reflex. Once the signals leave the Edinger Westphal nucleus, they remain on the same side. That is, they remain ipsilateral. So there is bilateral distribution of sensory signals into this circuitry. And then from the pretectum to the motor output there is once again bilateral distribution of information. But once we get to the parasympathetic motor nucleus the information is unilateral. Specifically it remains ipsilateral. Okay, now, I'm going to want you to think through systematically all the various perturbations of the pupillary light reflex. Imagine shining a light in one eye, and looking for constriction of the pupil. Shining a light in the opposite eye and doing the same. And imagine what you might see in a variety of patients. There will be hopefully, all of your patients, but we know sadly that won't be the case. Hopefully all of your patients will show symmetrical, bilateral constriction of the pupils. And this bilateral constriction is an indication that the signals are being processed in the pretectum, distributed bilaterally to the motor nuclei. And these signals are being sent along the efferent pathway to the constrictor muscles of the iris, leading to the symmetrical constriction of the pupils. Now if any of that is not observed, then you very well may have an injury to the eye, to the optic nerves, to the optic tract, to the circuitry of the pretectum, to the region of the Edinger-Westphal nucleus in the nerve roots of the third nerve. Or the path taken by those preganglionic or postganglionic axons out to the constrictor muscles of the iris. And it's your job as a clinician to reason through this circuitry and make a judgement as to whether you think there is a localized lesion. Now, our focus here is on the constriction of the pupil, but let me just say in passing, that there's also a dilation of the pupil that's under the governance of the sympathetic nervous system. And as you may recall the sympathetic outflow, comes preganglionic neurons, in the intermedial lateral cell column of the thoracic spinal cord. So there's a rather circuitous route that the neural signals take to get out of the brain into that sympathetic chain of ganglia and then back to the iris. So just keep in mind for our consideration here that pupillary constriction is under the governance of the parasympathetic outflow through the third nerve where as pupil dilation is under the governance of the sympathetic nervous system. So I'd like to leave you after this brief tutorial with three study questions and these are questions that will present clinical vignettes from three patients. each of whom has some sign associated with your performance of the pupillary light reflex. And your job is to consider whether there may be a localized lesion to either the sensory limb of this reflex, the motor limb or perhaps the central stations in the pretectum where sensation is integrated to produce motor action.