Neuroscience: How the brain prioritizes behaviors.

To optimize our choices, we need to prioritize among different goals. A recent study used a new Drosophila behavioral paradigm, bringing together conflicting behavioral choices in the context of different internal states and sensory cues, to provide foundational insights into the circuit mechanisms underlying how the brain prioritizes behavioral decisions.

Cellular metabolic reprogramming controls sugar appetite in Drosophila.

Cellular metabolic reprogramming is an important mechanism by which cells rewire their metabolism to promote proliferation and cell growth. This process has been mostly studied in the context of tumorigenesis, but less is known about its relevance for nonpathological processes and how it affects whole-animal physiology. Here, we show that metabolic reprogramming in Drosophila female germline cells affects nutrient preferences of animals. Egg production depends on the upregulation of the activity of the pentose phosphate pathway in the germline, which also specifically increases the animal's appetite for sugar, the key nutrient fuelling this metabolic pathway. We provide functional evidence that the germline alters sugar appetite by regulating the expression of the fat-body-secreted satiety factor Fit. Our findings demonstrate that the cellular metabolic program of a small set of cells is able to increase the animal's preference for specific nutrients through inter-organ communication to promote specific metabolic and cellular outcomes.

Nutrient homeostasis - translating internal states to behavior.

Behavioral neuroscience aims to describe a causal relationship between neuronal processes and behavior. Animals' ever-changing physiological needs alter their internal states. Internal states then alter neuronal processes to adapt the behavior of the animal enabling it to meet its needs. Here, we describe nutrient-specific appetites as an attractive framework to study how internal states shape complex neuronal processes and resulting behavioral outcomes. Understanding how neurons detect nutrient states and how these are integrated at the level of neuronal circuits will provide a multilevel description of the mechanisms underlying complex feeding and foraging decisions.

optoPAD, a closed-loop optogenetics system to study the circuit basis of feeding behaviors.

The regulation of feeding plays a key role in determining the fitness of animals through its impact on nutrition. Elucidating the circuit basis of feeding and related behaviors is an important goal in neuroscience. We recently used a system for closed-loop optogenetic manipulation of neurons contingent on the feeding behavior of Drosophila to dissect the impact of a specific subset of taste neurons on yeast feeding. Here, we describe the development and validation of this system, which we term the optoPAD. We use the optoPAD to induce appetitive and aversive effects on feeding by activating or inhibiting gustatory neurons in closed-loop - effectively creating virtual taste realities. The use of optogenetics allowed us to vary the dynamics and probability of stimulation in single flies and assess the impact on feeding behavior quantitatively and with high throughput. These data demonstrate that the optoPAD is a powerful tool to dissect the circuit basis of feeding behavior, allowing the efficient implementation of sophisticated behavioral paradigms to study the mechanistic basis of animals' adaptation to dynamic environments.

Sensorimotor pathway controlling stopping behavior during chemotaxis in the Drosophila melanogaster larva.

Sensory navigation results from coordinated transitions between distinct behavioral programs. During chemotaxis in the Drosophila melanogaster larva, the detection of positive odor gradients extends runs while negative gradients promote stops and turns. This algorithm represents a foundation for the control of sensory navigation across phyla. In the present work, we identified an olfactory descending neuron, PDM-DN, which plays a pivotal role in the organization of stops and turns in response to the detection of graded changes in odor concentrations. Artificial activation of this descending neuron induces deterministic stops followed by the initiation of turning maneuvers through head casts. Using electron microscopy, we reconstructed the main pathway that connects the PDM-DN neuron to the peripheral olfactory system and to the pre-motor circuit responsible for the actuation of forward peristalsis. Our results set the stage for a detailed mechanistic analysis of the sensorimotor conversion of graded olfactory inputs into action selection to perform goal-oriented navigation.

Role of the subesophageal zone in sensorimotor control of orientation in Drosophila larva.

Chemotaxis is a powerful paradigm to investigate how nervous systems represent and integrate changes in sensory signals to direct navigational decisions. In the Drosophila melanogaster larva, chemotaxis mainly consists of an alternation of distinct behavioral modes: runs and directed turns. During locomotion, turns are triggered by the integration of temporal changes in the intensity of the stimulus. Upon completion of a turning maneuver, the direction of motion is typically realigned toward the odor gradient. While the anatomy of the peripheral olfactory circuits and the locomotor system of the larva are reasonably well documented, the neural circuits connecting the sensory neurons to the motor neurons remain unknown. We combined a loss-of-function behavioral screen with optogenetics-based clonal gain-of-function manipulations to identify neurons that are necessary and sufficient for the initiation of reorientation maneuvers in odor gradients. Our results indicate that a small subset of neurons residing in the subesophageal zone controls the rate of transition from runs to turns-a premotor function compatible with previous observations made in other invertebrates. After having shown that this function pertains to the processing of inputs from different sensory modalities (olfaction, vision, thermosensation), we conclude that the subesophageal zone operates as a general premotor center that regulates the selection of different behavioral programs based on the integration of sensory stimuli. The present analysis paves the way for a systematic investigation of the neural computations underlying action selection in a miniature brain amenable to genetic manipulations.

Primate segmental duplication creates novel promoters for the LRRC37 gene family within the 17q21.31 inversion polymorphism region.

The LRRC37 gene family maps to a complex region of the human genome and has been subjected to multiple rounds of segmental duplication. We investigate the expression and regulation of this gene family in multiple tissues and organisms and show a testis-specific expression of this gene family in mouse but a more ubiquitous pattern of expression among primates. Evolutionary and phylogenetic analyses support a model in which new alternative promoters have been acquired during primate evolution. We identify two promoters, Cl8 and particularly Cl3, both of which are highly active in the cerebellum and fetal brain in human and have been duplicated from a promoter region of two unrelated genes, BPTF and DND1, respectively. Two of these more broadly expressed gene family members, LRRC37A1 and A4, define the boundary of a common human inversion polymorphism mapping to chromosome 17q21.31 (the MAPT locus)-a region associated with risk for frontal temporal dementia, Parkinsonism, and intellectual disability. We propose that the regulation of the LRRC37 family occurred in a stepwise manner, acquiring foreign promoters from BPTF and DND1 via segmental duplication. This unusual evolutionary trajectory altered the regulation of the LRRC37 family, leading to increased expression in the fetal brain and cerebellum.