Modification by sialylated glycans can affect protein functions, underlying mechanisms that control animal development and physiology. Sialylation relies on a dedicated pathway involving evolutionarily conserved enzymes, including CMP-sialic acid synthetase (CSAS) and sialyltransferase (SiaT) that mediate the activation of sialic acid and its transfer onto glycan termini, respectively. In Drosophila, CSAS and DSiaT genes function in the nervous system, affecting neural transmission and excitability. We found that these genes function in different cells: the function of CSAS is restricted to glia, while DSiaT functions in neurons. This partition of the sialylation pathway allows for regulation of neural functions via a glia-mediated control of neural sialylation. The sialylation genes were shown to be required for tolerance to heat and oxidative stress and for maintenance of the normal level of voltage-gated sodium channels. Our results uncovered a unique bipartite sialylation pathway that mediates glia-neuron coupling and regulates neural excitability and stress tolerance.

The basal ganglia (BG) contribute to reinforcement learning (RL) and decision making, but unlike artificial RL agents, it relies on complex circuitry and dynamic dopamine modulaton of opponent striatal pathways to do so. We develop the OpAL* model to assess the normative advantages of this circuitry. In OpAL*, learning induces opponent pathways to differentially emphasize the history of positive or negative outcomes for each action. Dynamic DA modulation then amplifies the pathway most tuned for the task environment. This efficient coding mechanism avoids a vexing explore-exploit tradeoff that plagues traditional RL models in sparse reward environments. OpAL* exhibits robust advantages over alternative models, particularly in environments with sparse reward and large action spaces. These advantages depend on opponent and nonlinear Hebbian plasticity mechanisms previously thought to be pathological. Finally, OpAL* captures risky choice patterns arising from DA and environmental manipulations across species, suggesting that they result from a normative biological mechanism.