Le Moing, C. L. | bioRxiv Science

bioRxiv2026

Mice with impaired synaptic facilitation exhibit deficits in cognitive flexibility

Behavioral flexibility is crucial to animal survival in dynamic environments, and a failure to update actions in response to recent outcomes is a hallmark of many neuropsychiatric disorders. However, the cellular and circuit mechanisms in the brain that support behavioral flexibility remain poorly understood. Forms of short-term plasticity such as synaptic facilitation have been theorized to transiently maintain information in neural circuits, and flexibly modulate how circuits process information depending on recent activity. Despite theoretical support, there is no direct experimental evidence linking synaptic facilitation to flexible decision-making. Recently, the presynaptic calcium sensor Synaptotagmin-7 (Syt7) has been shown to be required for synaptic facilitation at many synapses in the mammalian brain. Here, we assess operant learning in male and female Syt7 KO mice to determine how facilitation contributes to learning both stable and dynamic reward contingencies. We find that Syt7 KO mice acquired stable contingencies similarly to wild-type controls. However, KO mice were impaired in learning dynamic contingencies, showed more perseverative responding, and were delayed in applying a new task rule to all trial types following reversal. Behavioral modeling revealed a reduced influence of recent trial history on decisions in KO mice compared to wild-type controls. The behavioral deficits could not be explained by differences in motivation or memory. These results suggest that synaptic facilitation supports adaptive decision-making and that disruptions of short-term plasticity impair animals ability to use recent outcomes to update behavior.

neuroscience↗

bioRxiv2022

Responses to song playback differ in sleeping versus anesthetized songbirds

Vocal learning in songbirds is mediated by a highly localized system of interconnected forebrain regions, including recurrent loops that traverse the cortex, basal ganglia, and thalamus. This brain-behavior system provides a powerful model for elucidating mechanisms of vocal learning, with implications for learning speech in human infants, as well as for advancing our understanding of skill learning in general. A long history of experiments in this area has tested neural responses to playback of different song stimuli in anesthetized birds at different stages of vocal development. These studies have demonstrated selectivity for different song types that provide neural signatures of learning. In contrast to the ease of obtaining responses to song playback in anesthetized birds, song-evoked responses in awake birds are greatly reduced or absent, indicating that behavioral state is an important determinant of neural responsivity. Song-evoked responses can be elicited in sleeping as well as anesthetized zebra finches, and the selectivity of responses to song playback in adult birds tends to be highly similar between anesthetized and sleeping states, encouraging the idea that anesthesia and sleep are highly similar. In contrast to that idea, we report evidence that cortical responses to song playback in juvenile zebra finches (Taeniopygia guttata) differ greatly between sleep and urethane anesthesia. This finding indicates that behavioral states differ in sleep versus anesthesia and raises questions about relationships between developmental changes in sleep activity, selectivity for different song types, and the neural substrate for vocal learning. SignificancePatterns of spiking activity based on electrophysiological recordings in many different taxa are known to be heavily dependent on behavioral state. Neural activity patterns are frequently similar between sleep and anesthesia, which has encouraged the idea that similar states characterize sleep and anesthesia. Based on comparisons across studies, we report that activity patterns are highly dissimilar between sleep and urethane anesthesia in a cortical region of juvenile songbirds. These data argue against the idea that similar behavioral states are achieved in sleep versus anesthesia.

neuroscience↗