Regulation of electrical transmission by protein kinase C in Aplysia bag cell neurons

Electrical synapses are composed of gap junctions, made from paired hemi-channels that allow for the transfer of current from one neuron to another. Gap junctions mediate electrical transmission in neurons, where they synchronize spiking and promote rapid transmission, thereby influencing the coordination, pattern, and frequency of firing. In the marine snail, Aplysia calfornica, two clusters of neuroendocrine bag cell neurons use electrical synapses to synchronize a 30-min burst of action potentials, known as the afterdischarge, which releases egg-laying hormone and induces reproduction. In culture, paired bag cell neurons present a junctional conductance that is non-rectifying and largely voltage-independent. During the afterdischarge, PKC is activated, which is known to increase voltage-gated Ca2+ current; yet, little is understood as to how this pathway impacts electrical transmission. The transfer of presynaptic spike-like waveforms (generated in voltage-clamp) to the postsynaptic cell (measured in current-clamp) was monitored with or without PKC activation. It was found that pretreatment with the PKC activator, phorbol-12-myristate-13-acetate (PMA), enhanced junctional conductance between bag cell neurons. Furthermore, in control, presynaptic action potential waveforms mainly evoked postsynaptic electrotonic potentials at both -60 and -40 mV. However, with PKC activation the presynaptic stimulus consistently elicited postsynaptic action potentials from resting potentials of -40 mV, and would occasionally result in firing from repetitive input at -60 mV. Moreover, to assess whether this enhanced electrical transmission genuinely reflects a greater junctional conductance or a change in postsynaptic responsiveness, a fast-phase junctional-like current was applied to single bag cell neurons. Neurons in PMA always fired action potentials in response to current injection as opposed to control, which were less likely to spike. This outcome did not change when the junctional-like current was artificially enhanced in control conditions. Also, in response to fast- and slow-phase electrotonic potential (ETP) waveforms, Ca2+ current was markedly larger in single PMA-treated neurons. These findings suggest that PKC activation may contribute to afterdischarge fidelity by recruiting postsynaptic Ca2+ current to promote synchronous network firing. Finally, Aplysia gap junction genes (innexins) were transfected into mouse N2A cells and characterized. This revealed a biophysical and pharmacological profile similar to native gap junctions.

Retro-Neoliberalism: Elite Counter-Protest in Latin America, 1940-1975

This research challenges the origin story of neoliberalism in Latin America. Drawing on archival data from the Mont Pèlerin Society and the personal archives of leading but neglected figures in the post-war push to rebuild economic liberalism, I present a historical geography of elite counter-protest that both predates and broadens the generally accepted “birth” of neoliberalism in 1970s Chile. Beginning in the 1940s, Latin American elites found common cause with key figures from economic liberalism’s most radical wing: the Austrian School. While existing literature links the onset of neoliberalism in Chile to the Austrian School, particularly with respect to the School’s influence on the early Mont Pèlerin Society, this dissertation is the first comprehensive inquiry to place the Austrian tradition in the ideational and organizational landscape of Latin America. Embracing a new mission that promised to save the soul of Western civilization, Latin America’s retro-neoliberal leaders collaborated with transnational actors to build a network of Austrian-inspired think-tanks and institutes of higher learning in the region. These organizations, in turn, served as recruiting mechanisms to found the Hispanic quarter of the Mont Pèlerin Society, which was dominated not (as might be assumed) by Chileans, but rather by retro-neoliberal elites from Mexico, Argentina, Guatemala, and Venezuela. By 1975, when scholars began analyzing how a run-of-the-mill economics department had been transformed into a bastion of free-market thinking in Chile, an entire neoliberal university was up and running in Guatemala, exposing all students, regardless of discipline, to the Austrian tradition – the crowning achievement of Latin America’s retro-neoliberal network. Investigating, and accounting for, the development and impact of this initiative sheds new light on the neoliberal landscape in Latin America, and raises important questions for the study of neoliberalism more broadly.