Retinogeniculate (RG) synapses connect retinal ganglion cells to the thalamic relay cells of the dorsal lateral geniculate nucleus (dLGN). They are critical for regulating the flow of visual information from retina to primary visual cortex (V1). RG synapses in dLGN are uniquely larger and stronger than their counterparts in other retinorecipient regions. Moreover, in dLGN, RG synapses can be classified into two groups: simple RG synapses, which contain glia-encapsulated single RTs synapsing onto relay cell dendrites, and complex RG synapses, which contain numerous RTs that converge onto the shared regions of relay cell dendrites. To identify target-derived molecules that direct the transformation of RTs into unique RG synapses in dLGN, I used RNAseq to obtain the whole transcriptome of dLGN and its adjacent retinorecipient nucleus, vLGN, at different time points during RG synapses development. Leucine-Rich Repeat Transmembrane Neuronal 1 (LRRTM1), a synaptogenic adhesion molecule, was the candidate I selected based on its expression pattern. Here, I discovered that LRRTM1 regulates the development of complex RG synapses. Mice lacking LRRTM1 (lrrtm1-/-) not only show a significant reduction in the number of complex RG synapses but they exhibit abnormal visual behaviors. This work reveals, for the first time, a high level of retinal convergence onto dLGN relay cells in thalamus and the functional significance of this convergence for vision. / Ph. D. / Our relationship with the environment is heavily reliant on vision, an intricately wired sensory system, much like a circuit. This circuit begins at the eyes, with the retina, and spreads to different visual centers in the brain. Retinal ganglion cells (RGCs) send their wires, called axons, carrying information about the visual world to over 40 different regions in the brain. A major target of these axons is the dorsal lateral geniculate nucleus (dLGN), a region critical to our ability to perceive the visual world. The sites where RGCs connect to the dLGN cells are called retinogeniculate (RG) synapses, and my studies focused on understanding how these RG synapses develop and how they function. I am the first to discover the fact that more than a dozen distinct RGC axons cluster within the same neighborhood of one shared target cell in the dLGN. Unique to the dLGN, these clusters, termed complex RG synapses, are not seen in any other RGC target regions in the brain. Moreover, I demonstrated a new molecular mechanism that forms these synapses by identifying a protein called LRRTM1, as a critical molecule required for the formation of these complex RG synapses in the dLGN. By studying the visual behavior of mutant mice lacking LRRTM1, I demonstrated that complex RG synapses are important for performing complex visual tasks. The discoveries detailed within this dissertation add to current efforts to restore vision in patients suffering from severe visual impairments, via regenerative therapies, by furthering our understanding of how neural wires connect in the visual circuit to reveal everything we will ever know about the visual world.

No description available.

Thesis (Ph. D.)--West Virginia University, 2002. / Title from document title page. Document formatted into pages; contains x, 181 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 161-179).

Acute brain cell swelling (cytotoxic edema) can occur in the first minutes of stroke, presumably as a result of brain cells taking up water. In extreme hypo-osmotic situations such as excessive water-loading by patients, uptake by brain cells can expand the brain, causing seizures. But is ischemic brain cell swelling the same as hypo-osmotic swelling? Water can passively diffuse across the plasma membrane. However the presence of water channels termed aquaporins (AQP) facilitates passive water diffusion by 10-100 times. Unlike astrocytes, there is no evidence of water channels on neuronal plasma membrane. However, there is still much debate about which cells (neurons or astrocytes) swell during over-hydration or during stroke and if neurons and astrocytes can volume-regulate during osmotic stress. The purpose of this study was to examine and compare the volume responses of PyNs and magnocellular neuroendocrine cells (MNCs) to acute osmotic challenge and to OGD. We examined MNCs because they are intrinsically osmosensitive to small changes (2-3 mOsm) of plasma osmolality. We also examined if the same neurons behave similarly in brain slices or when dissociated and if they respond differently to acute osmotic stress and stroke-like stress. Our results indicate that during acute osmotic stress (±40 mOsm) half of dissociated PyNs and MNCs tended to show appropriate responses. MNCs in brain slices showed similar responses to when they were dissociated, while brain slice PyNs were less responsive than when dissociated. Exposure to OGD resulted in obvious differences between the two types of in vitro preparations. Dissociated PyNs and MNCs showed no consistency in their volume responses to 10 minutes of OGD. Dissociated neurons swelled, shrunk or were unchanged in about equal numbers. In contrast, brain slice PyNs underwent profound swelling whereas, brain slice MNCs showed minor volume decreases. We conclude that about half of our dissociated neurons were too variable and unpredictable in their osmotic volume responses to be useful for osmotic studies. They also were too resistant to stroke-like stress to be good models for ischemia. Brain slice neurons were similar in their osmotic responses to dissociated neurons but proved to have consistent and predictable responses to stroke-like stress. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2011-02-07 17:55:08.333

When an organism is dehydrated, neurons in the Organum vasculosum lamina terminalis (OVL T) sense this variation in plasma osmolality (OSM) and excite magnocellular neurosecretory cells (MNCs) in the supraoptic nucleus (SON) via glutamatergic synapses. The resulting action potential firing of MNCs will result in the secretion of vasopressin (VP) into the blood, which will promote water reabsorption from the kidney. The relationship between plasma VP and OSM (know as the VP-OSM ratio) is known to change in sensitivity during the course of a day. / Lorsqu'un organisme est déshydraté, les neurones dans l'Organum vasculosum lamina terminalis (OVL T) détectent le changement dans l'osmolalité du plasma (OSM) et excitent les cellules magnocellulaires neurosécrétoires (MNCs) dans le noyau supraoptique (SON) avec des synapses glutamatergique. La décharge des potentiels d'action qui survient dans les MNCs génère la sécrétion de vasopressine (VP) dans le sang, qui permettra la réabsorption d'eau au niveau du rein. Le rapport entre la VP et OSM (connu comme étant le rapport VP/OSM) subit des changements de sensibilité durant une journée.

Background: The neuropeptide S receptor (NPSR1) and its ligand neuropeptide S (NPS) have received increased attention in the last few years, as both establish a previously unknown system of neuromodulation. Animal research studies have suggested that NPS may be involved in arousal/wakefulness and may also have a crucial role in sleep regulation. The single nucleotide polymorphism (SNP) rs324981 in NPSR1 has begun to shed light on a function of the NPS-system in human sleep regulation. Due to an amino acid exchange, the T-allele leads to an increased sensitivity of the NPSR1. In the only genomewide association study to date on circadian sleep parameters in humans, an association was found between rs324981 and regular bedtime. However, the sleep parameters in this study were only measured by self-rating. Therefore, our study aimed to replicate these findings using an objective measure of sleep. Methods: The study included n = 393 white subjects (62–79 years) who participated in an actigraphic assessment for determining sleep duration, rest duration, sleep onset, rest onset and sleep onset latency. Genotyping of the SNP rs324981 was performed using the TaqMan OpenArray System. Results: The genotype at rs324981 was not significantly associated with rest onset (bedtime) or sleep onset (p = .146 and p = .199, respectively). However, the SNP showed a significant effect on sleep- and rest duration (p = .007 and p = .003, respectively). Subjects that were homozygous for the minor T-allele had a significantly decreased sleep- and rest duration compared to A-allele carriers. Conclusion: The results of this study indicate that the sleep pattern in humans is influenced by the NPS-system. However, the previously reported association between bedtime and rs324981 could not be confirmed. The current finding of decreased sleep duration in T/T allele carriers is in accordance with studies in rodents reporting similar results after NPS application.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 126-139).

Thesis (Ph. D.)--University of Missouri--Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 166-187). Also available on the Internet.