Precise temporal control of neuro-differentiation and postdifferentiation events is necessary for the creation of appropriate wiring diagram in the brain. To make advances in the treatment of neurodevelopmental and neurodegenerative disorders, and traumatic brain injury, it is important to understand these mechanisms. Caenorhabditis elegans has emerged as a revolutionary tool for the study of neural circuits due to its genetic homology to vertebrates and ease of genetic manipulation. microRNA (miRNA), a ubiquitous class of small non-coding RNA, that inhibits the expression of target genes, has emerged as an important timing control molecule through research conducted on C. elegans. This review will focus on the temporal control of neurodifferentiation and post-differentiation events exerted by the two conserved miRNAs, lin-4 and let-7. We summarize recent findings on the role of lin-4 as a timing regulator controlling transition of sequential events in neuronal pathfinding and synaptic remodeling, and the role of let-7 as a timing regulator that limits the regeneration potential of post-differentiated AVM neurons as they age.
PurposePreviously we found two types of corneal neurons that we hypothesized to play an important role in tearing. One type is called low threshold–cold sensitive plus dry sensitive (LT-CS + DS), and the other is termed high threshold–cold sensitive plus dry sensitive (HT-CS + DS). The present study examined critical stimuli influencing the activity of these neurons to elucidate environmental factors that may trigger this ocular reflex.MethodsSingle corneal neurons were extracellularly recorded from the trigeminal ganglia in response to ocular stimuli that mimic environmental conditions one encounters in daily life. They included an ocular desiccation and slight air currents and were presented while simultaneously monitoring the ocular surface temperatures (OST) in rats.ResultsThe results showed that the changes in steady state (SS) activity of the neurons closely followed the changes in SS OST: during the sustained ocular desiccation, neural firing displayed numerous small sudden increases in activities (“spiking”); these “spiking” activities of LT-CS + DS neurons were replicated by a minute air current that induced slight ocular surface cooling of approximately 0.2–0.1°C; and the responses of HT-CS + DS neurons showed an inconsistent relationship to the changes in SS OST or exhibited little evidence for “spiking” activities.ConclusionsThese results suggest that LT-CS + DS neurons play a role in the afferent trigger of tearing as we face the environment, exposing the cornea to prevailing air currents that produce a slight cooling of the ocular surface. By contrast, HT-CS + DS neurons may serve to protect the eyes from extreme dryness by eliciting nociception-evoked tearing when the OST or osmolarity of tears becomes injurious.
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