Biology subjects

Nunez, K. M.

Publications and source records attributed to Nunez, K. M..

3 recordsLinked to original sources

bioRxiv2025

Hunger Recruits a Parallel Circuit Encoding Alcohol Reward

Internal states like hunger, pain, thirst and arousal can bias behavior by affecting sensory and memory processing. Internal states are critical to understand in the context of alcohol addiction because they influence cravings, reinstatement, and relapse. Norepinephrine plays a key role in both hunger and alcohol-induced arousal and preference, but the circuit-level mechanisms through which it modulates the influence of hunger on alcohol preference are not well understood. We sought to address this using intersectional genetic tools for manipulating neurons expressing octopamine, the invertebrate analogue of vertebrate norepinephrine. We identified a single octopamine neuron required for ethanol seeking only when Drosophila are food-deprived. Hunger increased baseline activity in this neuron, making it more responsive to an odor cue previously paired with ethanol. A combination of genetic and connectome analyses revealed that synaptic partners of this octopaminergic neuron form a functional module that acts on Drosophila memory circuitry. Thus, we show that hunger recruits a parallel circuit that drives learned ethanol preference, providing a neuronal framework through which internal state influences the expression of memory for ethanol-associated cues.

neuroscience↗

bioRxiv2024

Inhibitory control of locomotor statistics in walking Drosophila

In order to forage for food, many animals regulate not only specific limb movements but the statistics of locomotor behavior over time, switching between long-range dispersal and localized search depending on resource availability. How pre-motor circuits regulate such locomotor statistics is not clear. Here we analyze and model locomotor statistics in walking Drosophila, and their modulation by attractive food odor. Odor evokes three motor regimes in flies: baseline walking, upwind running during odor, and search behavior following odor loss. During search behavior, we find that flies adopt higher angular velocities and slower ground speeds, and tend to turn for longer periods of time in one direction. We further find that flies spontaneously adopt periods of different mean ground speed, and that these changes in state influence the length of odor-evoked runs. We next developed a simple model of neural locomotor control that suggests that contralateral inhibition plays a key role in regulating the statistical features of locomotion. As the fly connectome predicts decussating inhibitory neurons in the lateral accessory lobe (LAL), a pre-motor structure, we gained genetic access to a subset of these neurons and tested their effects on behavior. We identified one population of neurons whose activation induces all three signature of search and that bi-directionally regulates angular velocity at odor offset. We identified a second group of neurons, including a single LAL neuron pair, that bi-directionally regulate ground speed. Together, our work develops a biologically plausible computational architecture that captures the statistical features of fly locomotion across behavioral states and identifies potential neural substrates of these computations.

neuroscience↗

bioRxiv2019

Circuits that encode and predict alcohol associated preference.

Substance use disorders are chronic relapsing disorders often impelled by enduring memories and persistent cravings. Alcohol, as well as other addictive substances, remolds neural circuits important for memory to establish obstinate preference despite aversive consequences. How pertinent circuits are selected and shaped to result in these unchanging, inflexible memories is unclear. Using neurogenetic tools available in Drosophila melanogaster we define how circuits required for alcohol associated preference shift from population level dopaminergic activation to select dopamine neurons that predict behavioral choice. During memory expression, these dopamine neurons directly, and indirectly via the mushroom body (MB), modulate the activity of interconnected glutamatergic and cholinergic output neurons. Transsynaptic tracing of these output neurons revealed at least two regions of convergence: 1) a center of memory consolidation within the MB implicated in arousal, and 2) a structure outside the MB implicated in integration of naive and learned responses. These findings provide a circuit framework through which dopamine neuron activation shifts from reward delivery to cue onset, and provides insight into the inflexible, maladaptive nature of alcohol associated memories.

neuroscience↗