RESUMO
Melanopsin-dependent phototransduction in intrinsically photosensitive retinal ganglion cells (ipRGCs) involves a Gq-coupled phospholipase C (PLC) signaling cascade. Acetylcholine, released in the mammalian retina by starburst amacrine cells, can also activate Gq-PLC pathways through certain muscarinic acetylcholine receptors (mAChRs). Using multielectrode array recordings of rat retinas, we demonstrate that robust spiking responses can be evoked in neonatal and adult ipRGCs after bath application of the muscarinic agonist carbachol. The stimulatory action of carbachol on ipRGCs was a direct effect, as confirmed through calcium imaging experiments on isolated ipRGCs in purified cultures. Using flickering (6 Hz) yellow light stimuli at irradiances below the threshold for melanopsin activation, spiking responses could be elicited in ipRGCs that were suppressed by mAChR antagonism. Therefore, this work identified a novel melanopsin-independent pathway for stimulating sustained spiking in ganglion cell photoreceptors. This mAChR-mediated pathway could enhance ipRGC spiking responses in conditions known to evoke retinal acetylcholine release, such as those involving flickering or moving visual stimuli. Furthermore, this work identifies a pharmacological approach for light-independent ipRGC stimulation that could be targeted by mAChR agonists.
Assuntos
Potenciais de Ação/fisiologia , Estimulação Luminosa/métodos , Células Fotorreceptoras/fisiologia , Receptores Muscarínicos/fisiologia , Células Ganglionares da Retina/fisiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Carbacol/farmacologia , Agonistas Colinérgicos/farmacologia , Antagonistas Muscarínicos/farmacologia , Técnicas de Cultura de Órgãos , Células Fotorreceptoras/efeitos dos fármacos , Ratos , Ratos Long-Evans/parasitologia , Células Ganglionares da Retina/efeitos dos fármacosRESUMO
An overall 44% transplacental transmission rate was observed in 221 rats fed cysts of 12 Toxoplasma strains at 15 days of pregnancy, with a range of 0-90% transmission. Considerable variability in the transmission rate was seen among different groups of rats that received similar Toxoplasma inocula; this is attributed to genetically based susceptibility to Toxoplasma among individuals of the outbred Wistar strain of rats. Transplacental transmission was more frequent in Long Evans than in Wistar rats. Significant differences in the rate of transmission were not found between rats that were fed similar Toxoplasma inocula 6-8 days or 15 days after conception. The frequency of transmission was not affected by the strain or dose of Toxoplasma used.
