Biology subjects

Baz, E.-S.

Publications and source records attributed to Baz, E.-S..

7 recordsLinked to original sources

bioRxiv2026

Neprilysin 1 in the Mushroom Body controls Feeding behavior by regulating SIFamide levels in Drosophila melanogaster

Feeding-related behavior in Drosophila melanogaster encompasses olfactory and gustatory detection of odors, foraging, and food intake. In Drosophila melanogaster, the neuropeptide SIFamide (SIFa), has been shown to integrate hunger signals to promote feeding in Drosophila and is considered a central regulator of mutually exclusive behavioral states. Here, we identify the mushroom bodies as a key downstream circuit of SIFamidergic neurons for regulation of food-seeking and feeding. Furthermore, we show that mushroom bodies are not merely downstream effectors but actively shape SIFamidergic signaling through the peptidase Neprilysin 1 for which SIFamide is a substrate. Thus, SIFa signaling is embedded within a feedforward-feedback circuit that couples internal state to the selection and execution of feeding behavior. We propose that the distinct neuronal subtypes postsynaptic to the elaborately arborized SIFamidergic neurons define discrete neuronal subroutines that differentially control the mutually exclusive behaviors related to sexual reproduction, sleep and feeding. Our findings reveal an evolutionary ancient peptidergic system that is modified by recruitment of novel genes for the flexible control of distinct behavioral programs and feeding strategies.

animal behavior and cognition↗

bioRxiv2025

Presynaptic Release Probability Determines the Need for Sleep

Sleep is universal among animals with synapses, yet the synaptic functions determining the need for sleep remain elusive. By directly measuring synaptic transmission at anatomically defined synapses in Drosophila, we found that synaptic strength remained stable or declined after sleep deprivation in a circuit-specific manner. In contrast, presynaptic release probability (Pr) consistently decreased with sleep loss across circuits and species, stemming from reduced Ca2+ influx or weakened vesicle-channel coupling at presynaptic terminals, and recovered after sleep. Bidirectional manipulations of Pr altered sleep pressure, establishing a causal relationship between presynaptic function and sleep need. Non-synaptic sleep-regulatory signaling pathways consistently modulate Pr but not synaptic strength. Thus, our findings identify Pr, rather than synaptic strength, as the conserved synaptic substrate underlying sleep need.

neuroscience↗

bioRxiv2025

Sleep Facilitates Pattern Separation through SK Channel-Mediated Sparse Coding

The roles of sleep in priming the brain for associative learning remain unclear. Here, we report that acute sleep deprivation in Drosophila selectively impairs pattern separation--the ability to distinguish between similar stimuli--without affecting classical conditioning. This deficit correlates with disrupted sparse coding in the mushroom body, reflected by an increased number of active Kenyon cells and greater overlap in their odor representations. Electrophysiological analyses reveal that sleep loss enhances small conductance calcium-activated potassium (SK) channel-mediated afterhyperpolarization in GABAergic anterior paired lateral (APL) neurons, leading to reduced levels of feedback inhibition onto Kenyon cells and compromised sparse coding. Targeted knockdown of SK channels in APL neurons reduce their augmented afterhyperpolarization and rescues the pattern separation deficits caused by sleep deprivation. These findings identify a critical role for SK channels in inhibitory interneurons to enable sleep to preserve sparse and decorrelated neural representations, supporting cognitive processes such as pattern separation.

neuroscience↗

bioRxiv2024

A High-Throughput Platform for Assessing Single Fly Learning and Memory: Individual Drosophila Olfactory Conditioner (iDOC)

Olfactory conditioning in Drosophila melanogaster is a widely used behavioral paradigm for uncovering the neural basis of learning and memory. The traditional T-maze assay, however, relies on group-level assessments and cannot examine individual flies learning and memory abilities. To address this limitation, we developed the Individual Drosophila Olfactory Conditioner (iDOC), an apparatus for single-fly conditioning and memory assessment. Using iDOC, we demonstrated aversive olfactory learning, short-term memory (STM), anesthesia-resistant memory (ARM), and protein synthesis-dependent long-term memory (LTM) in individual flies, consistent with previous experiments conducted using the T-maze. As an individual memory assessment method, iDOC can be integrated with other behavioral assays at the single animal level, such as sleep monitoring. Notably, we found that spaced training, which induces LTM, also promotes post-learning sleep, while massed training, which induces ARM, did not. iDOC thus provides a powerful platform for investigating learning and memory and its interplay with other behavioral processes at the individual animal level. HighlightsO_LIDeveloped iDOC for high-throughput, single-fly aversive olfactory training and memory assessment C_LIO_LIDemonstrated aversive learning, STM, ARM, and LTM in individual flies using iDOC C_LIO_LISpaced conditioning, and not massed conditioning, promotes sleep C_LI

animal behavior and cognition↗

bioRxiv2024

Behavioral screening defines three molecular Parkinsonism subgroups in Drosophila

Parkinsonism is defined by motor dysfunction, but the specific upstream molecular causes of these clinical symptoms can vary widely. We hypothesize that these causes converge onto a limited number of core cellular pathways. To investigate this, we created a new collection of 24 genetically very well-controlled animal models of familial forms of parkinsonism. Using unbiased behavioral screening and machine learning we identified three clusters of mutants that converge on (1) mitochondrial function; (2) retromer/vesicle trafficking; and (3) proteostasis/autophagy. Genes within each cluster have a similar genetic interaction profile and compounds that target specific molecular pathways ameliorate dopaminergic neuron dysfunction in a cluster-specific manner. This suggests that familial parkinsonism can be stratified into three broad functional groups and our findings pave the way for targeted biomarker discovery and drug development.

neuroscience↗

bioRxiv2023

Single-cell transcriptomics reveals that glial cells integrate homeostatic and circadian processes to drive sleep-wake cycles

The sleep-wake cycle is determined by circadian and sleep homeostatic processes. However, the molecular impact of these processes and their interaction in different brain cell populations remain unknown. To fill this gap, we profiled the single-cell transcriptome of adult Drosophila brains across the sleep-wake cycle and four circadian times. We show cell type-specific transcriptomic changes with glia displaying the largest variation. Glia are also among the few cell types whose gene expression correlates with both sleep homeostat and circadian clock. The sleep-wake cycle and sleep drive level affect expression of clock gene regulators in glia, while diminishing the circadian clock specifically in glia impairs homeostatic sleep rebound after sleep deprivation. These findings reveal a comprehensive view of the effects of sleep homeostatic and circadian processes on distinct cell types in an entire animal brain and reveal glia as an interaction site of these two processes to determine sleep-wake dynamics.

animal behavior and cognition↗

bioRxiv2020

Astroglial Calcium Signaling Encodes Sleep Need in Drosophila

Sleep is under homeostatic control, whereby increasing wakefulness generates sleep need and triggers sleep drive. However, the molecular and cellular pathways by which sleep need is encoded are poorly understood. In addition, the mechanisms underlying both how and when sleep need is transformed to sleep drive are unknown. Here, using ex vivo and in vivo imaging, we show in Drosophila that astroglial Ca2+ signaling increases with sleep need. We demonstrate that this signaling is dependent on a specific L-type Ca2+ channel and is required for homeostatic sleep rebound. Thermogenetically increasing Ca2+ in astrocytes induces persistent sleep behavior, and we exploit this phenotype to conduct a genetic screen for genes required for the homeostatic regulation of sleep. From this large-scale screen, we identify TyrRII, a monoaminergic receptor required in astrocytes for sleep homeostasis. TyrRII levels rise following sleep deprivation in a Ca2+-dependent manner, promoting further increases in astrocytic Ca2+ and resulting in a positive-feedback loop. These data suggest that TyrRII acts as a gate to enable the transformation of sleep need to sleep drive at the appropriate time. Moreover, our findings suggest that astrocytes then transmit this sleep need to the R5 sleep drive circuit, by upregulation and release of the interleukin-1 analog Spatzle. These findings define astroglial Ca2+ signaling mechanisms encoding sleep need and reveal dynamic properties of the sleep homeostatic control system.

neuroscience↗