The Effects of Neurosteroids, such as Pregnenolone Sulfate and its receptor, TrpM3 in the Retina.

Pregnenolone sulfate (PregS) is the precursor to all steroid hormones and is produced in neurons in an activity dependent manner. Studies have shown that PregS production is upregulated during certain critical periods of development, such as in the first year of life in humans, during adolescence, and during pregnancy. Conversely, PregS is decreased during aging, as well as in several neurodevelopmental and neurodegenerative conditions. There are several known targets of PregS, such as a positive allosteric modulator NMDA receptors, sigma1 receptor, and as a negative allosteric modulator of GABA-A receptors. Recently a transient receptor potential channel, TrpM3 has been shown to be activated by PregS. TrpM3 is a heat sensitive (between 33-40oC), non-selective cation channel that is outwardly rectifying. PregS has been shown to increase the frequency of post-synaptic currents in the hippocampus and developing cerebellum, induce calcium transients in a subset of retinal ganglion cells, and enhance memory formation in rodents. Furthermore, PregS mediated TrpM3 activation induces calcium dependent transcription of early immediate genes, suggesting that activation of this channel may produce lasting effects on cells and systems in which it is activated. Because PregS is abundant during critical periods of development, we hypothesized that it may play a significant role during development. Furthermore, the role of PregS or its receptor TrpM3, has not previously been well characterized in the retina. To address this question, in this dissertation, we examine the role of the neurosteroid PregS and its receptor, TrpM3, on retinal waves, which are characteristic of specific stages of synaptic development and connectivity. Briefly, we show that PregS induces a TrpM3 dependent prolonged calcium transient, which is absent in the TrpM3-/- animals and increases the correlation of cell participation in waves. We also show that TrpM3 increases the frequency of post-synaptic currents, indicating a mechanism of action presynaptic to retinal ganglion cells, but that TrpM3 is expressed primarily in RGCs and Müller glia. Taken together, our results indicate that both PregS and TrpM3 are important in modulating spontaneous synaptic activity during development

Looking for safe harbor in a crowded sea: Coastal space use conflict and marine renewable energy development

Technological advances in the marine renewable energy industry and increased clarity about the leasing and licensing process are fostering development proposals in both state and federal waters. The ocean is becoming more industrialized and competition among all marine space users is developing (Buck et al. 2004). More spatial competition can lead to conflict between ocean users themselves, and to tensions that spill over to include other stakeholders and the general public (McGrath 2004). Such conflict can wind up in litigation, which is costly and takes agency time and financial resources away from other priorities. As proposals for marine renewable energy developments are evaluated, too often decision-makers lack the tools and information to properly account for the cumulative effects and the tradeoffs associated with alternative human uses of the ocean. This paper highlights the nature of marine space conflicts associated with marine renewable energy literature highlights key issues for the growth of the marine renewable energy sector in the United States. (PDF contains 4 pages

Government decision making during a crisis: the New Zealand experience during the Covid-19 pandemic

A key component of New Zealand’s response to the Covid-19 pandemic was how the government was organised and supported to make decisions in relation to the health, economic, social, foreign policy, legal and other policy issues it faced. The New Zealand system of central government decision making, as set out in the Cabinet Manual and operated by the Cabinet Office, was continually adapted to ensure that the Prime Minister and Ministers, and the officials working to them, were provided with a system that facilitated both rapid and considered decision making and promulgation of those decisions

Experience and motivation shape leader-follower interactions in fish shoals

Leadership is an important process shaping collective movement in some species. Recent work has demonstrated that experienced or motivated individuals can emerge as leaders, and provides insight into the mechanisms by which this occurs. Ultimately, leadership depends upon the effectiveness with which would-be leaders can entrain followers, and while the properties of leaders have received much attention, less is known about the factors that affect the propensity of their groupmates to follow them. Here the roles of experience and state (hunger) in shaping leader and follower behavior were investigated using shoals of sticklebacks (Gasterosteus aculeatus). A first experiment revealed that individuals trained to approach a target could entrain and lead their naïve groupmates out of a refuge towards it, and that they did so more effectively when they (the trained fish) were food-deprived. In the second experiment the hunger level of the trained fish was held constant, while that of the naïve fish was varied. Here, leadership by trained fish was only apparent when the hunger levels of the naïve group members were intermediate. When naïve fish were recently fed they took a long time to visit the target and their arrival times were not affected by the presence of a trained individual. Very hungry groups recruited to the target most rapidly, but again with no evidence of influence by their trained groupmates. These experiments demonstrate that leadership in animal groups depends not only upon the state and experience of the leader but also upon that of the potential followers.PostprintPeer reviewe