Crosstalk between biochemical signaling and trafficking determines AMPAR dynamics in synaptic plasticity

Synaptic plasticity involves the modification of both biochemical and structural components of neurons. Many studies have revealed that the change in the number density of the glutamatergic receptor AMPAR at the synapse is proportional to synaptic weight update; increase in AMPAR corresponds to strengthening of synapses while decrease in AMPAR density weakens synaptic connections. The dynamics of AMPAR are thought to be regulated by upstream signaling, primarily the calcium-CaMKII pathway, trafficking to and from the synapse, and influx from extrasynaptic sources. Here, we have developed a set of models using compartmental ordinary differential equations to systematically investigate contributions of signaling and trafficking variations on AMPAR dynamics at the synaptic site. We find that the model properties including network architecture and parameters significantly affect the integration of fast upstream species by slower downstream species. Furthermore, we predict that the model outcome, as determined by bound AMPAR at the synaptic site, depends on (a) the choice of signaling model (bistable CaMKII or monostable CaMKII dynamics), (b) trafficking versus influx contributions, and (c) frequency of stimulus. Therefore, AMPAR dynamics can have unexpected dependencies when upstream signaling dynamics (such as CaMKII and PP1) are coupled with trafficking modalities.

Energy versus safety: unilateral action, voter welfare, and executive accountability

Does increasing executive power necessarily decrease accountability? To answer this question, I develop a two-period signaling model comparing voter welfare in two separation-of-powers settings. In one, the executive works with a median legislator to change policy; in the other, the executive chooses between legislation or unilateral action. Both politicians may have preferences that diverge from the voter's, yet I find that increasing executive power may increase accountability and welfare, even in some cases when the legislator is more likely to share the voter's preferences than the executive. Unilateral power allows a congruent executive to overcome gridlock, implement the voter's preferred policy, and reveal information about the politicians’ types—which can outweigh the risks of a divergent executive wielding power for partisan ends.

Security Transitions

How do foreign powers disengage from a conflict? We study this issue by examining the recent, large-scale security transition from international troops to local forces in the ongoing civil conflict in Afghanistan. We construct a new dataset that combines information on this transition process with declassified conflict outcomes and previously unreleased quarterly survey data of residents’ perceptions of local security. Our empirical design leverages the staggered roll-out of the transition, and employs a novel instrumental variables approach to estimate the impact. We find a significant, sharp, and timely decline of insurgent violence in the initial phase: the security transfer to Afghan forces. We find that this is followed by a significant surge in violence in the second phase: the actual physical withdrawal of foreign troops. We argue that this pattern is consistent with a signaling model, in which the insurgents reduce violence strategically to facilitate the foreign military withdrawal to capitalize on the reduced foreign military presence afterward. Our findings clarify the destabilizing consequences of withdrawal in one of the costliest conflicts in modern history, and yield potentially actionable insights for designing future security transitions. (JEL D74, F51, F52, O17)

Phospho-dependent Signaling during the General Stress Response by the Atypical Response Regulator and ClpXP Adaptor RssB

ABSTRACTIn the model organism Escherichia coli and related species, the general stress response relies on tight regulation of the intracellular levels of the promoter specificity subunit RpoS. RpoS turnover is exclusively dependent on RssB, a two-domain response regulator that functions as an adaptor that delivers RpoS to ClpXP for proteolysis. Here we report crystal structures of the receiver domain of RssB both in its unphosphorylated form and bound to the phosphomimic BeF3−. Surprisingly, we find only modest differences between these two structures, suggesting that truncating RssB may partially activate the receiver domain to a “meta-active” state. Our structural and sequence analysis points to RssB proteins not conforming to either the Y-T coupling scheme for signaling seen in prototypical response regulators, such as CheY, or to the signaling model of the less understood FATGUY proteins.

Reputation Concerns in Risky Experimentation

High-ability agents are more likely to achieve early success in risky experimentation, but learn faster that their project is not promising. These counteracting effects give rise to a signaling model with double-crossing property. This property tends to induce homogenization of quitting times between types, which in turn leads to some pooling in equilibrium. Low-ability agents may hold out to continue their project for the prospect of pooling with the high type, despite having a negative instantaneous net payoff. A war-of-attrition mechanism causes low-ability agents to quit only gradually over time, and to stop quitting for a period immediately before all agents exit.

What’s in a Name? That Which We Call Capital Controls

This paper investigates why controls on capital inflows have a bad name by tracing how capital controls have been used and perceived since the laissez-faire era of the classical gold standard. While advanced economies often employed capital controls to tame inflows during the last century, we conjecture that several factors undermined their subsequent use—most notably, a “guilt by association” with controls on capital outflows, which have typically been employed by autocratic regimes or those with failed macroeconomic policies. We formalize the idea of a possible guilt by association between inflow controls and outflow controls in a signaling model and provide some empirics consistent with it.