Biology subjects

Keles, M. F.

Publications and source records attributed to Keles, M. F..

6 recordsLinked to original sources

bioRxiv2023

Deep Phenotyping of Sleep in Drosophila

Animal behavior depends on internal state. While subtle movements can signify significant changes in internal state, computational methods for analyzing these "microbehaviors" are lacking. Here, we present FlyVISTA, a machine-learning platform to characterize microbehaviors in freely-moving flies, which we use to perform deep phenotyping of sleep. This platform comprises a high-resolution closed-loop video imaging system, coupled with a deep-learning network to annotate 35 body parts, and a computational pipeline to extract behaviors from high-dimensional data. FlyVISTA reveals the distinct spatiotemporal dynamics of sleep-associated microbehaviors in flies. We further show that stimulation of dorsal fan-shaped body neurons induces micromovements, not sleep, whereas activating R5 ring neurons triggers rhythmic proboscis extension followed by persistent sleep. Importantly, we identify a novel microbehavior ("haltere switch") exclusively seen during quiescence that indicates a deeper sleep stage. These findings enable the rigorous analysis of sleep in Drosophila and set the stage for computational analyses of microbehaviors.

neuroscience↗

bioRxiv2023

A subclass of evening cells promotes the switch from arousal to sleep at dusk

Animals exhibit rhythmic patterns of behavior that are shaped by an internal circadian clock and the external environment. While light intensity varies across the day, there are particularly robust differences at twilight (dawn/dusk). These periods are also associated with major changes in behavioral states, such as the transition from arousal to sleep. However, the neural mechanisms by which time and environmental conditions promote these behavioral transitions are poorly defined. Here, we show that the E1 subclass of Drosophila evening clock neurons promotes the transition from arousal to sleep at dusk. We first demonstrate that the cell-autonomous clocks of E2 neurons alone are required to drive and adjust the phase of evening anticipation, the canonical behavior associated with "evening" clock neurons. We next show that conditionally silencing E1 neurons causes a significant delay in sleep onset after dusk. However, rather than simply promoting sleep, activating E1 neurons produces time- and light- dependent effects on behavior. Activation of E1 neurons has no effect early in the day, but then triggers arousal before dusk and induces sleep after dusk. Strikingly, these phenotypes critically depend on the presence of light during the day. Despite their influence on behavior around dusk, in vivo voltage imaging of E1 neurons reveals that their spiking rate does not vary between dawn and dusk. Moreover, E1-specific clock ablation has no effect on arousal or sleep. Thus, we suggest that, rather than specifying "evening" time, E1 neurons act, in concert with other rhythmic neurons, to promote behavioral transitions at dusk.

neuroscience↗

bioRxiv2020

A visual pathway for skylight polarization processing in Drosophila

Many insects use patterns of polarized light in the sky to orient and navigate. Here we functionally characterize neural circuitry in the fruit fly, Drosophila melanogaster, that conveys polarized light signals from the eye to the central complex, a brain region essential for the flys sense of direction. Neurons tuned to the angle of polarization of ultraviolet light are found throughout the anterior visual pathway, connecting the optic lobes with the central complex via the anterior optic tubercle and bulb, in a homologous organization to the sky compass pathways described in other insects. We detail how a consistent, map-like organization of neural tunings in the peripheral visual system is transformed into a reduced representation suited to flexible processing in the central brain. This study identifies computational motifs of the transformation, enabling mechanistic comparisons of multisensory integration and central processing for navigation in the brains of insects.

neuroscience↗

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↗

bioRxiv2018

Cell-type specific patterned stimulus-independent neuronal activity in the Drosophila visual system during synapse formation

Stereotyped synaptic connections define the neural circuits of the brain. In vertebrates, stimulus-independent activity contributes to neural circuit formation. It is unknown whether this type of activity is a general feature of nervous system development. Here, we report patterned, stimulus-independent neural activity in the Drosophila visual system during synaptogenesis. Using in vivo calcium, voltage, and glutamate imaging, we found that all neurons participate in this spontaneous activity, which is characterized by brain-wide periodic active and silent phases. Glia are active in a complementary pattern. Each of the 15 examined of the over 100 specific neuron types in the fly visual system exhibited a unique activity signature. The activity of neurons that are synaptic partners in the adult was highly correlated during development. We propose that this cell type-specific activity coordinates the development of the functional circuitry of the adult brain.

neuroscience↗

bioRxiv2016

Hypercomplex properties of Drosophila object detecting neurons

Many animals rely on vision to detect objects such as conspecifics, predators, and prey. Hypercomplex cells of the feline cortex and small target motion detectors of the dragonfly and hoverfly optic lobe demonstrate robust tuning for small objects with weak or no response to elongated edges or movement of the visual panorama [1-4]. However, the relationship between anatomical, molecular, and functional properties of object detection circuitry is not understood. Here, we characterize a previously identified lobula columnar neuron (LC11) in Drosophila [5]. By imaging calcium dynamics with two-photon excitation microscopy we show that LC11 responds to the non-directional motion of a small object darker than the background, with little or no responses to static flicker, elongated bars, or panoramic gratings. LC11 dendrites reside at the boundary between GABA-ergic and cholinergic layers of the lobula, each dendrite spans enough columns to sample 75-degrees of visual space, yet the functional receptive field is only 20-degrees wide, and shows robust responses to an object spanning less than one 5-degree facet of the compound eye. The dendrites of neighboring LC11s encode object motion retinotopically, but the axon terminals fuse into a glomerular structure in the central brain where retinotopy is lost. Blocking inhibitory ionic currents abolishes small object sensitivity and facilitates responses to elongated bars and gratings. Our results reveal high acuity small object motion detection in the Drosophila optic lobe.

neuroscience↗