Biology subjects

Kaun, K. R.

Publications and source records attributed to Kaun, K. R..

7 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↗

bioRxiv2021

The foraging gene affects alcohol sensitivity, metabolism and memory in Drosophila

The genetic basis of alcohol use disorder (AUD) is complex. Understanding how natural genetic variation contributes to alcohol phenotypes can help identify mechanisms underlying the genetic contribution of AUD. Recently, a single nucleotide polymorphism in the human foraging (for) gene ortholog, Protein Kinase cGMP-Dependent 1 (PRKG1), was found to be associated with stress-induced risk for alcohol abuse. However, the mechanistic role that PRKG1 plays in AUD is not well understood. We use natural variation in the Drosophila for gene to describe how variation of cGMP-dependent protein kinase (PKG) activity modifies ethanol-induced phenotypes. We found that variation in for affects ethanol-induced increases in locomotion and memory of the appetitive properties of ethanol intoxication. Further, these differences may stem from the ability to metabolize ethanol. Together, this data suggests that natural variation in PKG modulates cue reactivity for alcohol, and thus could influence alcohol cravings by differentially modulating metabolic and behavioral sensitivities to alcohol.

genetics↗

bioRxiv2021

Neuromolecular and behavioral effects of ethanol deprivation in Drosophila

Alcohol use disorder (AUD) is characterized by loss of control in limiting alcohol intake. This may involve intermittent periods of abstinence followed by alcohol seeking and, consequently, relapse. However, little is understood of the molecular mechanisms underlying the impact of alcohol deprivation on behavior. Using a new Drosophila melanogaster repeated intermittent alcohol exposure model, we sought to identify how ethanol deprivation alters spontaneous behavior, determine the associated neural structures, and reveal correlated changes in brain gene expression. We found that repeated intermittent ethanol-odor exposures followed by ethanol-deprivation dynamically induces behaviors associated with a negative affect state. Although behavioral states broadly mapped to many brain regions, persistent changes in social behaviors mapped to the mushroom body and surrounding neuropil. This occurred concurrently with changes in expression of genes associated with sensory responses, neural plasticity, and immunity. Like social behaviors, immune response genes were upregulated following three-day repeated intermittent ethanol-odor exposures and persisted with one or two days of ethanol-deprivation, suggesting an enduring change in molecular function. Our study provides a framework for identifying how ethanol deprivation alters behavior with correlated underlying circuit and molecular changes.

neuroscience↗

bioRxiv2020

Transsynaptic mapping of Drosophila mushroom body output neurons

The Mushroom Body (MB) is a well-characterized associative memory structure within the Drosophila brain. Although previous studies have analyzed MB connectivity and provided a map of inputs and outputs, a detailed map of the downstream targets is missing. Using the genetic anterograde transsynaptic tracing tool, trans-Tango, we identified divergent projections across the brain and convergent downstream targets of the MB output neurons (MBONs). Our analysis revealed at least three separate targets that receive convergent input from MBONs: other MBONs, the fan shaped body (FSB), and the lateral accessory lobe (LAL). We describe, both anatomically and functionally, a multilayer circuit in which inhibitory and excitatory MBONs converge on the same genetic subset of FSB and LAL neurons. This circuit architecture provides an opportunity for the brain to update information and integrate it with previous experience before executing appropriate behavioral responses. Highlights-The postsynaptic connections of the output neurons of the mushroom body, a structure that integrates environmental cues with associated valence, are mapped using trans-Tango. -Mushroom body circuits are highly interconnected with several points of convergence among mushroom body output neurons (MBONs). -The postsynaptic partners of MBONs have divergent projections across the brain and convergent projections to select target neuropils outside the mushroom body important for multimodal integration. -Functional connectivity suggests the presence of multisynaptic pathways that have several layers of integration prior to initiation of an output response.

neuroscience↗

bioRxiv2020

Behavioral features of motivated response to alcohol in Drosophila

Animals avoid predators and find the best food and mates by learning from the consequences of their behavior. However, reinforcers are not always uniquely appetitive or aversive but can have complex properties. Most intoxicating substances fall within this category; provoking aversive sensory and physiological reactions while simultaneously inducing overwhelming appetitive properties. Here we describe the subtle behavioral features associated with continued seeking for alcohol despite aversive consequences. We developed an automated runway apparatus to measure how Drosophila respond to consecutive exposures of a volatilized substance. Behavior within this Behavioral Expression of Ethanol Reinforcement Runway (BEER Run) demonstrated a defined shift from aversive to appetitive responses to volatilized ethanol. Behavioral metrics attained by combining computer vision and machine learning methods, reveal that a subset of 9 classified behaviors and component behavioral features associate with this shift. We propose this combination of 9 behaviors can be used to navigate the complexities of operant learning to reveal motivated goal-seeking behavior.

animal behavior and cognition↗

bioRxiv2019

Alcohol causes lasting differential transcription in Drosophila mushroom body neurons

Repeated alcohol experiences can produce long-lasting memories for sensory cues associated with intoxication. These memories can ultimately trigger relapse in individuals recovering from alcohol use disorder (AUD). The molecular mechanisms by which alcohol changes memories to become long-lasting and inflexible remain unclear. New methods to analyze gene expression within precise neuronal cell-types can provide further insight towards AUD prevention and treatment. Here, we employed genetic tools in Drosophila melanogaster to investigate the lasting consequences of ethanol on transcription in memory-encoding neurons. Drosophila rely on mushroom body (MB) neurons to make associative memories, including memories of ethanol-associated sensory cues. Differential expression analyses found that distinct transcripts, but not genes, in the MB were associated with experiencing ethanol alone compared to forming a memory of an odor cue associated with ethanol. These findings reveal the dynamic and highly context-specific regulation of splicing associated with encoding behavioral experiences. Our data thus demonstrate that alcohol can have lasting effects on transcription and RNA processing during memory formation, and identify new transcript targets for future AUD and addiction investigation.

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↗