Observations are presented of a combined light and electron microscopic study of synaptogenesis in the photoreceptor terminal of visuallycompetent mice. Our study suggests that photoreceptor synaptogenesis in these retina progresses through a sequence of postnatal changes which leads to the ordered arrangement of processes within the adult photoreceptor terminal. On the 5th postnatal day, neuronal processes form synaptic contacts with a photoreceptor terminal, usually in the vicinity of a synaptic ribbon. Following the formation of synaptic contacts, the processes invaginate into the photoreceptor terminal, maintaining their position, lateral to a synaptic ribbon. Beginning on about the 10th day, a central process enters the terminal to yield a triad configuration which is a characteristic of a mature photoreceptor terminal. The formation of triads is essentially complete by the 14th postnatal day.Our observations suggest that horizontal cell processes form synaptic contacts with the photoreceptor terminal before bipolar cell dendrites, implying that the horizontal cells mature in advance of the bipolar cells. This possibility is discussed in terms of the appearance of the electroretinogram (ERG) in the developing mouse retina.

The influence of photoreceptor degeneration upon synaptogenesis in the photoreceptor terminal of developing retinae of rd mice (C3H/HeJ and C57BL rd Ze) is outlined and compared to the sequential development of the photoreceptor terminals of the retinae of normal mice. The initial phases of synaptogenesis in the photoreceptor terminal of the rd retina appear normal during the first postnatal week. Appositional contacts form between the photoreceptor terminal and neuronal processes before invagination of horizontal processes occurs to form a dyad configuration. A virtual absence of triad configurations in the photoreceptor terminal suggests that synaptogenesis is arrested in the photoreceptor terminal of the rd retina between the 7th and 10th day, at which time the central (bipolar) process normally invaginates into the photoreceptor terminal. During this period, photoreceptor cell death proceeds rapidly but few signs of degeneration are aaparent. It is suggested that the inherited abnormality influences the maturation of bipolar cells more than that of horizontal cells. The b-wave component of the electroretinogram (EilG) of the immature rd retina is discussed in terms of photoreceptor/bipolar cell synaptic contacts.In the retinal-degenerative mouse, a mutation ( r d ) has occurred in gene linkage group XVII which is transmitted as an autosomal recessive characteristic ( Sidman and Green, '65). Expression of the mutation ( r d ) has been shown to be restricted to the retina where it is lethal to all the photoreceptor cells and possibly some bipolar cells. Observations with light microscopy (Noell, '58) and electron microscopy (Sonohara and Shiose, '68; Shiose and Sonohara, '69; Caley, Johnson and Liebelt, '72) show that the degeneration first appears on the 8th postnatal day in the inner segments. Later, the developing outer segments disintegrate and, finally, pyknosis of the nuclei occurs; by 18 days, the outer nuclear layer is reduced to a single layer of photoreceptor nuclei.While the most striking pathological changes occur in the photoreceptor layer, there are suggestions that cells within the inner layers of the retinae of rd mice are affected by the inherited disease. Biochemical studies of cyclic AMP metabolism J. COMP. NEUR., 156: 95-106.

We have prepared highly purified cultures of rat oligodendrocytes by a modification of the procedure of McCarthy and de Vellis [1980]. By utilizing a substratum derived from lysed glia and a calf serum-containing medium with a high concentration of transferrin, the oligodendrocyte cultures display a high degree of purity, the ability to survive several months of culture, and a striking ability to produce a myelin-like membrane. We have examined the production of this myelin-like membrane using immunocytochemical and biochemical probes as well as an extensive morphological examination at the electron microscopic level. The membrane appears to be produced in a similar developmental pattern to that observed in vivo and it has the structural characteristics of loosely packed central nervous system myelin.

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Because hypoxic inhibition of fetal breathing may be caused by a rise in central adenosine levels, the effects of O2 deficiency on fetal brain adenosine concentrations were determined at levels of hypoxia that inhibited fetal breathing. Under halothane anesthesia, the brains of fetal sheep (0.8 term) were implanted with guide cannulas exteriorized through a Silastic rubber window in the uterus and flank of the ewe. At least 4 days after surgery, a microdialysis probe was inserted into a cannula with the membrane tip placed in the rostral brain stem. During 1 h of isocapnic hypoxia, mean fetal arterial PO2 was reduced from 24.0 +/- 0.9 Torr (control) to 13 +/- 0.6 Torr and arterial pH fell progressively from 7.354 +/- 0.007 to 7.273 +/- 0.023. Hypoxia decreased the incidence of fetal breathing movements from 33 +/- 5.2 to 5 +/- 2.2 min/h, with a normal incidence (29 +/- 3.5 min/h) during the hour after arterial PO2 returned to control values. Adenosine concentrations in microdialysis perfusate under control conditions averaged approximately 35 nM, increased up to 2.3-fold during the hour of O2 deficiency, and fell toward control values when normoxia was restored. We conclude that fetal brain adenosine levels are increased at levels of O2 deficiency that inhibit fetal breathing, which are results consistent with a role for adenosine in hypoxic inhibition of fetal breathing.