No abstract

The rodent hippocampus exhibits population activities called sharp waves (SPWs) during slow wave sleep and wake immobility. SPWs are important for hippocampal-cortical communication and memory consolidation, and abnormal sharp wave-ripple complexes are closely related to epileptic seizures. Although the SPWs are known to arise from the CA3 circuit, the local mechanisms underlying their generation are not fully understood. We hypothesize that endogenous adenosine is a local regulator of hippocampal SPWs. We tested this hypothesis in thick mouse hippocampal slices that encompass a relatively large hippocampal circuit and have a high propensity of generating spontaneous in vitro SPWs. We found that application of adenosine A1 receptor antagonists induced in vitro SPWs and that such induction was sensitive to blockade by NMDA receptor antagonists. By contrast, an increase in endogenous adenosine via pharmacological inhibition of adenosine transporters or adenosine degrading enzymes suppressed spontaneous in vitro SPWs. We thus suggest that the initiation and incidence of sharp wave-like population events are under tight control by the activity of endogenously stimulated A1 receptors.

Perceptual decisions are complete when a continuously updated score of sensory evidence reaches a threshold. In Drosophila, αβ core Kenyon cells (αβc KCs) of the mushroom bodies integrate odor-evoked synaptic inputs to spike threshold at rates that parallel the speed of olfactory choices. Here we perform a causal test of the idea that the biophysical process of synaptic integration underlies the psychophysical process of bounded evidence accumulation in this system. Injections of single brief, EPSP-like depolarizations into the dendrites of αβc KCs during odor discrimination, using closed-loop control of a targeted opsin, accelerate decision times at a marginal cost of accuracy. Model comparisons favor a mechanism of temporal integration over extrema detection and suggest that the optogenetically evoked quanta are added to a growing total of sensory evidence, effectively lowering the decision bound. The subthreshold voltage dynamics of αβc KCs thus form an accumulator memory for sequential samples of information.