Imagine a mysterious puzzle box that encodes the duration between two stimuli. Scientists have discovered that within the brain’s cerebellar Purkinje cells lies an engram—a special group of cells—that holds the key to this interval encoding. When the first stimulus, known as the conditional stimulus (CS), is presented, it activates the engram, causing a pause in the firing rate of the cell. This pause precisely times the blink response to the second stimulus, the unconditional stimulus (US). By developing a sophisticated Bayesian algorithm, researchers have been able to uncover important details about this enigmatic process.

The algorithm reveals that the pause is characterized by a single, unusually long interspike interval. Its onset and offset latencies, as well as their trial-to-trial variability, mirror the timing of the CS-US interval. Interestingly, there is no decline in firing rate between the onset of the CS and the onset of the pause. Instead, a step-like transition occurs. Furthermore, each reading of the engram is triggered by a single pre-synaptic spike volley, and subsequent volleys do not affect the pause parameters.

This fascinating research not only sheds light on how our brain encodes and measures time intervals but also hints at potential molecular-level structures responsible for this process. To delve deeper into this captivating study on cell-intrinsic duration-encoding engrams, check out the full article!

The engram encoding the interval between the conditional stimulus (CS) and the unconditional stimulus (US) in eyeblink conditioning resides within a small population of cerebellar Purkinje cells. CSs activate this engram to produce a pause in the spontaneous firing rate of the cell, which times the CS-conditional blink. We developed a Bayesian algorithm that finds pause onsets and offsets in the records from individual CS-alone trials. We find that the pause consists of a single unusually long interspike interval. Its onset and offset latencies and their trial-to-trial variability are proportional to the CS-US interval. The coefficient of variation (CoV = σ/μ) are comparable to the CoVs for the conditional eye blink. The average trial-to-trial correlation between the onset latencies and the offset latencies is close to 0, implying that the onsets and offsets are mediated by two stochastically independent readings of the engram. The onset of the pause is step-like; there is no decline in firing rate between the onset of the CS and the onset of the pause. A single presynaptic spike volley suffices to trigger the reading of the engram; and the pause parameters are unaffected by subsequent volleys. The Fano factors for trial-to-trial variations in the distribution of interspike intervals within the intertrial intervals indicate pronounced non-stationarity in the endogenous spontaneous spiking rate, on which the CS-triggered firing pause supervenes. These properties of the spontaneous firing and of the engram read out may prove useful in finding the cell-intrinsic, molecular-level structure that encodes the CS-US interval.

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