The development of the mechanical characteristics of contraction and the pharmacology of synaptic activation in chick iris and ciliary body were examined from embryonic day 9 through posthatching. The ciliary ganglion-target muscle system has proven to be a useful model for both in vivo and in vitro studies of neuron-target interactions; one such interaction is involved in neuronal cell death, which in the ciliary ganglion occurs from Stage (St) 34 to 40. To understand the mechanism by which cholinergic blocking agents prevent naturally occurring neuronal death in the chick ciliary ganglion (see the following paper, Meriney et al., 1987), it was necessary to determine the effect of these agents on synaptic transmission at target structures during the cell death period. Initially (St 34-36), iris muscle contraction are synaptically mediated via muscarinic ACh receptors (AChRs) on myoepithelial cells, which have the contractile and structural characteristics of smooth muscle. Close apposition of synaptic terminals, similar to that described for mature synapses, was observed on these myoepithelial cells. Subsequently (St 37), the striated muscle fibers that appear are activated by nicotinic receptors, although muscarinic AChRs are also present. Mechanically, this can be seen as gradually changing from a slow-onset contraction, elicited only by 30 Hz stimulation, to a fast-twitch response (St 37-44). Dilator fibers that develop later in the iris (at about St 39) also possess nicotinic and muscarinic receptors. The ciliary body musculature, although not extensively studied, also appears to have dual cholinergic activation during development. The mature iris has predominately striated muscle fibers that have both junctional nicotinic and muscarinic (mostly extrajunctional) AChRs. The dual presence of both receptor types in the same muscle fiber was confirmed with intracellular recordings, in which only the initial portion of the ACh-elicited depolarization was sensitive to alpha bungarotoxin (alpha BTX). In addition, specific muscarinic binding sites were described in the developing, as well as in the mature, iris. The developing chick iris was also shown to contract directly in response to light, this response disappearing after hatching. This unique dual-receptor pharmacology (nicotinic-muscarinic) and light response of a striated muscle may be due to the neural crest origin of these cells.

We have described in the preceding 2 papers the development of the pharmacological and contractile properties of all targets of the ciliary ganglion: the iris and ciliary body (Pilar et al., 1987), and the choroidal coat (Meriney and Pilar, 1987). In this paper, we examine the chronic effects of ACh receptor (AChR) blockade on ciliary ganglion neuron survival. Nicotinic or muscarinic AChR blockers were administered daily to developing chicken embryos during the normal neuronal death period in the ciliary ganglion. The effects of the blockers on ganglionic and neuromuscular transmission were assessed, and neuronal survival was assayed by counting both the total number of ganglion neurons and the selectively HRP-labeled ciliary neurons after the normal neuronal death period. Blockade of ganglionic transmission decreases survival in both populations of neurons. Blockade of neuromuscular muscular transmission increases survival in the ciliary population, which innervates the striated iris and ciliary body muscle. In contrast, blockade of synaptic activity has various influences on the survival of the choroid population, which innervates the smooth muscle of the choroid coat. Smooth muscle muscarinic receptor blockade with atropine does not influence survival. At higher doses (which block ganglionic transmission), atropine decreases choroid survival. Survival of the choroid population is increased by nicotinic blockade with 75 micrograms alpha bungarotoxin (alpha BTX), but decreased by 12.5 micrograms alpha BTX. Two main conclusions arise from these studies. Activation of postsynaptic AChRs in both the ganglion and the periphery are important in the regulation of neuronal survival. These effects usually occur in opposite directions: Blockade of ganglionic transmission decreases neuronal survival, while paralysis of neuromuscular transmission increases neuronal survival. This embodies the "balance" hypothesis (Cunningham, 1982) for neuronal survival, which states that motoneurons must balance afferent and target interactions during a critical period after synapses are formed in both regions. The present observations support this hypothesis. However, although both ciliary and choroid neurons have been shown to depend on the presence of the periphery for survival, target muscle paralysis via AChR blockade rescues the ciliary neurons but does not influence survival in the choroid population. Target-dependent regulation of choroid neuron survival during the normal neuronal death period is clearly different from the regulation of ciliary neuron survival.

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Cell number, size, and somatotopic arrangement within the spinal ganglia of the cells of origin of the rat dorsal penile nerve (DPN), and their spinal cord projections, were studied by loading the proximal stump of the severed DPN with horseradish peroxidase (HRP). The DPN sensory cells were located entirely in the sixth lumbar (L6) dorsal root ganglia (DRG), in which a mean of 468 +/- 78 cells per side were observed, measuring 26.7 +/- 0.8 microns in their longest axis (range 10-65 microns) and distributed apparently randomly within the ganglia. Within the spinal cord, no retrograde label was found, i.e., no motoneurons were labeled, indicating that in the rat the DPN is formed exclusively of sensory nerve fibers. Although labeled fibers entered the cord only through L6, transganglionically transported HRP was evident in all spinal segments examined, i.e., T13-S2. Labeled fibers projected along the inner edge of the dorsal horn (medial pathway) throughout their extensive craniosacral distribution. However, laminar distribution varied with spinal segment. In the dorsal horn, terminals or preterminal axons were found in the dorsal horn marginal zone (lamina I), the substantia gelatinosa (lamina II), the nucleus proprius (laminae III and IV--the most consistent projection), Clarke's column (lamina VI), and the dorsal gray commissure. In the ventral horn, terminals were found in lamina VII and lamina IX. Label apposed to cell somas and dendrites in lamina VII may represent direct primary afferent projections onto sympathetic autonomic neurons. In lamina IX, labeled terminals delineated the somas and dendrites of cells that appeared to be motoneurons. This is the first description of an apparently monosynaptic contact onto motoneurons by a primary afferent of nonmuscle origin.

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A 69-year-old woman diagnosed with papillary thyroid carcinoma was treated with total thyroidectomy and radioiodine ablation. At follow-up a whole body I-131 scan after injection of rhTSH was performed. This scan shows unexpected uptake in the superior mediastinum, initially misinterpreted as metastases (Tg level: 6.8 ng/mL). CT and digital subtraction angiography (DSA) confirmed that this finding was due to an aortic aneurysm. This vascular malformation was embolized and endoprosthesis was performed using a Seldinger's technique.

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