Cerebrospinal fluid (CSF)‐contacting neurons form a part of the circumventricular organs of the central nervous system. Represented by different cytologic types and located in different regions, they constitute a CSF‐contacting neuronal system, the most central periventricular ring of neurons in the brain organized concentrically according to our concept. Because the central nervous system of deuterostomian echinoderm starfishes and the prochordate lancelet is composed mainly of CSF‐contacting‐like neurons, we hypothesize that this cell type represents ancient cells, or protoneurons, in the vertebrate brain. Neurons may contact the ventricular CSF via their dendrites, axons, or perikarya. Most of the CSF‐contacting nerve cells send their dendritic processes into the ventricular cavity, where they form ciliated terminals. These ciliated endings resemble those of known sensory cells. By means of axons, the CSF‐contacting neurons also may contact the external CSF space, where the axons form terminals of neurohormonal type similar to those known in the neurohemal areas. The most simple CSF‐contacting neurons of vertebrates are present in the terminal filum, spinal cord, and oblongate medulla. The dendritic pole of these medullospinal CSF‐contacting neurons terminates with an enlargement bearing many stereocilia in the central canal. These cells are also supplied with a 9 × 2 + 2 kinocilium that may contact Reissner's fiber, the condensed secretory material of the subcommissural organ. The Reissner's fiber floating freely in the CSF leaves the central canal at the caudal open end of the terminal filum in lower vertebrates, and open communication is thus established between internal CSF and the surrounding tissue spaces. Resembling mechanoreceptors cytologically, the spinal CSF‐contacting neurons send their axons to the outer surface of the spinal cord to form neurosecretory‐type terminals. They also send collaterals to local neurons and to higher spinal segments. In the hypothalamic part of the diencephalon, neurons of two circumventricular organs, the paraventricular organ and the vascular sac, of the magnocellular neurosecretory nuclei and several parvocellular nuclei, form CSF‐contacting dendritic terminals. A CSF‐contacting neuronal area also was found in the telencephalon. The CSF‐contacting dendrites of all these areas bear solitary 9 × 2 + 0 cilia and resemble chemoreceptors and developing photoreceptors cytologically. In electrophysiological experiments, the neurons of the paraventricular organ are highly sensitive to the composition of the ventricular CSF. The axons of the CSF‐contacting neurons of the paraventricular organ and hypothalamic nuclei terminate in hypothalamic synaptic zones, and those of magno‐ and parvocellular neurosecretory nuclei also form neurohormonal terminals in the median eminence and neurohypophysis. The axons of the CSF‐contacting neurons of the vascular sac run in the nervus and tractus sacci vasculosi to the nucleus (ganglion) sacci vasculosi. Some hypothalamic CSF‐contacti...

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The cerebrospinal fluid (CSF) contacting neurons have a dendritic process which protrudes into the central canal, and is provided with one long kinocilium and many shorter stereocilia (about 80 in the turtle) as revealed by scanning electron mecroscopy. The shape, number and arrangement of the cilia are similar to those of known receptor endings. The silver impregnated axons of these cells converge to a paired centrosuperficial tract forming terminal enlargements at the ventrolateral surface of the spinal cord. Lying among glial endfeet these terminals are ultrastructurally similar to those present in known neurosecretory areas. The nerve endings are attached to the basal lamina, and they comprise many synaptic vesicles (200 to 400 A in diameter), as well as granular vesicles of different sizes (diameter 600 to 1800 A). The axons may lie within finger-like protrusions on the surface of the spinal cord, or they may terminate around vesseles. Morphological evidence suggests that these nerve terminals and the corresponding CSF contacting perikarya represent a spinal neurosecretory system possibly influenced by information taken up by its special dendrites protruding into the inner CSF space.

The pinealocytes of fishes, amphibians, reptiles, birds and mammals have been compared with cerebrospinal fluid (CSF) contacting neurons. We found that the intraventricular dendrite terminal of the latter resembles the pinealocytic inner segment and that the atypical cilium (9x2+0 tubules) of the CSF contacting neurons is analogous with the outer segment of the pinealocytes, even though the outer segment bears photoreceptor lamellae in lower vertebrates. Regular, but small-sized photoreceptor outer segments were also found on pinealocytes of the chicken. In mammals, too, primitive outer segments are present in the form of 9x2 to cilia similar to those of CSF contacting dendritic terminals. In the Golgi areas of the perikarya of both cell types there are granulated vesicles which may contain transmitter substances and/or neurohormones. The synaptic junctions of the pinealocytes differ from those in the CSF contacting neurons. Many synapses occur on the latter, but they appear only rarely on pinealocytes. The axons of the CSF contacting neurons form synaptic connections with other cells, or terminate as neurohormonal synaptic hemidesmosomes on the basal lamina of the brain surface. The pinealocyte axons give rise to terminals containing synaptic ribbons. Such ribbons do not occur in CSF contacting neurons. In Lacertilians, we found pinealocytic terminals without ribbons on dendrite-like profiles. On the basis of the ultrastructural comparisons, we consider the CSF contacting neurons and pinealocytes to be very similar, but not to represent precisely the same cell type.

Cerebrospinal fluid (CSF)-contacting neurons were studied by means of electron microscopy in the spinal cord and/or terminal ventricle of the ray, Raja clavata (Elasmobranchii), the opossum, Didelphis virginiana (Marsupialia), the mouse, Mus musculus, and the guinea pig, Cavia cobaya (Rodentia). Dendrites of the CSF-contacting neurons in the spinal cord of the ray penetrate the ependyma of the central canal and form terminals bearing stereocilia. Axons apparently belonging to these neuronal perikarya terminate on the basal lamina of the spinal cord near the fila of the radix ventralis. In the opossum, a representative of metatherian mammals, the dendritic terminals of the CSF-contacting neurons resemble those of the phylogenetically ancient lower vertebrates and are endowed with many stereocilia. In such eutherian mammals as the mouse and the guinea pig, the corresponding stereocilia are usually less developed. There are numerous CSF-contacting neurons in the wall of the terminal ventricle of the mouse. Since the dendritic terminals of the spinal CSF-contacting neurons resemble those of known sensory cells and the axon terminals on the basal lamina resemble ultrastructurally neurosecretory endings, we suppose that the former are receptive to stimuli exerted by the internal (ventricular) CSF and capable of translating them into a neurosecretory output directed toward the external (subarachnoid) CSF. With their periradicular terminations the axons of the CSF-contacting neurons establish an extended, special site for neurosecretory release along the ventrolateral sulcus of the ray spinal cord.