The control of retinogeniculate transmission in the mammalian lateral geniculate nucleus

Summary In the mammalian visual system, the lateral geniculate nucleus is commonly thought to act merely as a relay for the transmission of visual information from the retina to the visual cortex, a relay without significant elaboration in receptive field properties or signal strength. However, many morphological and electrophysiological observations are at odds with this view. Only 10–20% of the synapses found on geniculate relay neurons are retinal in origin. Roughly half of all synapses derive from cells in layer VI of visual cortex; roughly one third are inhibitory and GABAergic, derived either from interneurons or from cells of the nearby perigeniculate nucleus. Most of the remaining synapses probably derive from cholinergic, noradrenergic, and serotonergic sites within the brainstem reticular formation. Moreover, recent biophysical studies have revealed several ionic currents present in virtually all thalamic neurons. One is a Ca²⁺-dependent K⁺ current underlying the afterhyperpolarization (or the I_AHP), which may last up to 100–200 ms following an action potential. Activation of the I_AHP leads to spike frequency adaptation in response to a sustained, suprathreshold input. Intracellular recordings from other neuronal preparations have shown that the I_AHP can be blocked by noradrenalin or acetylcholine, leading to an increased cellular excitability. Another ionic current results from a voltage- and time-dependent Ca²⁺ conductance that produces a low threshold spike. Activation of this conductance transforms a geniculate neuron from a state of faithful relay of information to one of bursting behavior that bears little relationship to the activity of its retinal afférents. We propose that state-dependent gating of geniculate relay cells, which may represent part of the neuronal substrate involved in certain forms of selective visual attention, can be effected through at least three different mechanisms: (1) conventional GABAergic inhibition, which is largely controlled via brainstem and cortical afferents through interneurons and perigeniculate cells; (2) the I_AHP, which is controlled via noradrenergic and cholinergic afferents from the brainstem reticular formation; and (3) the low threshold spike, which may be controlled by GABAergic inputs, cholinergic inputs, and/or the corticogeniculate input, although other possibilities also exist. Furthermore, it seems likely that gating functions involving the corticogeniculate pathway are suited to attentional processes within the visual domain (e.g., saccadic suppression), whereas brain-stem inputs seem more likely to have more global effects that switch attention between sensory systems. In any case, it is now abundantly clear that geniculate circuitry and the intrinsic electrophysiological properties of geniculate neurons are no longer compatible with the notion that the lateral geniculate nucleus serves as a simple relay.     

An autoradiographic study of chondrocyte transformation into chondroclasts and osteocytes during bone formation In vitro

Excised mouse pubic bone rudiments were exposed to H³-thymidine. Rudiments preserved immediately after exposure consisted of mesenchyme with a large number of cells showing intense radioactivity. Rudiments incubated on a filter membrane after exposure went through the developmental stages of complete chondrification of the pubic rami followed by periosteal and then endochondral bone formation. Only chondrocytes showed radioactivity in rami consisting of cartilage and periosteal bone that were preserved prior to endochondral ossification. Cell types showing radioactivity in rami preserved during endochondral ossification were chondrocytes, chondroclasts, and osteoblasts and osteocytes of endochondral bone. The results of the study demonstrated that hypertrophic chondrocytes of the calcified cartilage of a developing mammalian long bone not only survive dissolution of their matrix, but transform into chondroclasts and osteoprogenitor cells that give rise to osteoblasts and osteocytes which form endochondral bone in the absence of blood vessels.     

Ultrastructural and biochemical aspects of liver mitochondria during recovery from ethanol-induced alterations. Experimental evidence of mitochondrial division.

To study the morphologic and biochemical changes occuring in liver mitochondria during recovery from ethanol-induced injury, rats fed a 6-month high-alcohol regimen plus a nutritionally adequate diet which did not induce fatty liver were compared with isocalorically fed controls. After this period the alcohol-fed animals displayed striking ultrastructural changes of liver mitochondria and a decreased respiratory activity with succinate or malate-glutamate as substrate. On the contrary, the respiratory rate with I-glycerophosphate was 50% increased. Regression changes were studied after alcohol was withdrawn from the diet. Enlarged mitochondria rapidly disappeared (in 24 hours), although a few megamitochondria were still present after 8 days of abstinence. A similar recovery was observed for the functional alterations. At the end of the experimental period, only a slight decrease of the maximal respiratory rate using malate-glutamate as a substrate was noted. The ultrastructural findings and the morphometric data suggest that the way in which mitochondrial normalization takes place is based on partition of these organelles.     

The Binding of Different Lectins on Peripheral Blood Mononuclear Cells from Patients with Chronic Inflammatory and Malignant Diseases

Peripheral blood mononuclear cells from patients with multiple myeloma, gastrointestinal tumors, and inflammatory bowel disease were analyzed for binding of various lectins. The results demonstrated that in most of the patients with multiple myeloma a significantly increased percentage of cells positive for Lotus tetragonolobus agglutinin (LTA), peanut agglutinin (PNA), soybean agglutinin (SBA), and wheat germ agglutinin (WGA), and a decreased number of Agaricus bisporus agglutinin (ABA) positive cells were present as compared to a normal control group. This could not be shown in malignant or inflammatory disorders of the gastrointestinal tract where only some patients exhibited an increased PNA and LTA binding, respectively. Patients with the systemic malignant disease differed from patients with solid localized tumors by a significantly altered number of ABA, LTA and SBA-positive peripheral blood mononuclear cells. Double fluorescence studies using monoclonal antibodies and lectins revealed that most of the cells expressing receptors for ABA had also receptors for OKT3, whereas most of the cells with receptors for LTA, PNA SBA, and WGA were found to be positive for OKM.     

The effect of long-term irradiation with fluorescent light on the rat fundus

In the rat, continous exposure to so-called cold light of 800 lux leads to a nearly complete loss of retinal photoreceptors, which occurs within 4 weeks. This process is followed by vascularization of the retinal pigment epithelium (RPE). The origin, extent, and expansion of such proliferations within 6 months after the onset of irradiation were evaluated by means of light microscopy, transmission electron microscopy, scanning electron microscopy, corrosion cast preparation, india ink injection, and trypsin digest preparation. The vessels within the RPE were found to be fenestrated and to form a network with the vessels of the neurosensory retina. Invasion of Bruch's membrane and formation of chorioretinal anastomoses were not observed. The occurrence of vessels within the RPE coincided with a massive regression of capillaries in the neurosensory retina.     

N-Mannich-Base Prodrugs of 5-Iodo-2′-deoxycytidine as Topical Delivery Enhancers

Two Mannich-base prodrugs of 5-iodo-2-deoxycytidine (5-IDC) have been synthesized. The prodrugs exhibit increased lipid solubility compared to 5-IDC and rapidly revert to 5-IDC in buffer. One of the prodrugs delivered about twice as much 5-IDC from isopropyl myristate (IPM) through hairless mouse skin in diffusion-cell experiments as did 5-IDC from IPM. Subsequent applications of theophylline/ propylene glycol onto the diffusion cells to determine the effect of prodrug/IPM, 5-IDC/IPM, or IPM on the resistance of the skins to subsequent applications showed that the prodrug/IPM had no more effect than IPM itself.