Sleep deprivation results in diverse patterns of synaptic scaling across the Drosophila mushroom bodies

Abstract

Amount of pre-synaptic BRP in mushroom bodies is inversely related to recent sleep d Increased BRP after sleep loss is restricted specifically to Kenyon cells d Outputs from KCs to different synaptic partners show varied changes with sleep loss

Roles for Sleep in Neural and Behavioral Plasticity: Reviewing Variation in the Consequences of Sleep Loss

“…While even a brief nap restores memory in some assays (Seugnet et al, 2008 ; Ong et al, 2020 ), other learning and memory impairments persist after days of recovery sleep (Havekes et al, 2016 ; Yamazaki et al, 2020 ; Wu et al, 2021 ). While it is not clear why recovery from sleep loss varies between these conditions, studies have detected several types of longer-lasting cellular and molecular changes that persist after recovery sleep, including altered gene expression (Gaine et al, 2021 ), protein synthesis (Tudor et al, 2016 ; Lamon et al, 2021 ), and circuit connectivity (Weiss and Donlea, 2021 ). Interestingly, some types of memories seem to be more vulnerable to sleep loss than others.…”

“…Since sleep loss prior to training can impair acquisition/short-term memory and disrupting sleep after training prevents memory consolidation (Ganguly-Fitzgerald et al, 2006 ; Seugnet et al, 2008 ), it is likely that sleep deprivation alters either synaptic connectivity or plasticity in MB circuits. Overnight sleep deprivation selectively upscales synapses of cholinergic memory-encoding KCs, but not other cell types in the MB, including DANs or large, inhibitory interneurons (Weiss and Donlea, 2021 ). Further, not all types of KC output synapses are equally impacted by sleep loss; output connections from KCs to different classes of post-synaptic target neurons show wide variations in abundance following sleep loss.…”

“…While appetitive memory is encoded in the KC>MBON-γ2α'1 circuit in fed flies and is sensitive to sleep loss, appetitive memory is encoded in KC>MBON-γ1pedc circuitry in starved flies, and remains intact with sleep loss (Chouhan et al, 2021 ). Additionally, Weiss and Donlea ( 2021 ) found that sleep loss led to decreased connectivity between KCs and MBON-γ2α'1, necessary for sleep-dependent memory consolidation, while KC>MBON-γ1pedc connections, dispensable for sleep-dependent memory consolidation, were unaffected. Sleep loss could therefore disrupt consolidation of recent appetitive memories in fed flies by reducing overall connectivity between KCs and MBON-γ2α'1 (see Figure 1 ).…”

“…After SD, KC>MBON-γ1pedc connectivity is unchanged, but KC>MBON-γ2α'1 connectivity decreases. Based on findings from Weiss and Donlea ( 2021 ) and Chouhan et al ( 2021 ).…”

“…These studies in both mice and Drosophila suggest that increased cholinergic signaling disrupts learning and memory after sleep deprivation, and that inhibitory drive onto memory-encoding neurons could be recruited to compensate. While these studies find complementary effects of sleep loss in the fly and mouse, these results use different approaches; Weiss and Donlea ( 2021 ) measure synaptic active zone reporters in the fly MB while Delorme et al ( 2021 ) and Puentes-Mestril et al ( 2021 ) quantify hippocampal transcript levels of activity-dependent immediate early genes. Additional studies will be required to directly test the relationship between connectivity changes and cell-type specific changes in activity.…”