Biology subjects

Yu, A. L.

Publications and source records attributed to Yu, A. L..

5 recordsLinked to original sources

bioRxiv2026

An adaptive noradrenergic-prefrontal circuit for innate avoidance of heights

Innate preferences determine how animals interact with the environment, but how experience refines the neural processes underlying those intrinsic motivations is not well understood. Here we develop a virtual pole descent task which permitted in which mice can repeat many trials without habituation of height-dependent avoidance. Mice adjusted their choices based on recent trial outcomes without externally imposed behavioral reinforcement or punishment. Using this paradigm, we found that noradrenergic signaling enhances height avoidance while experience refines the prefrontal cortex population representation of the task. Inhibiting locus coeruleus norepinephrine neurons reduced safe choices in apparently tall visual height stimuli, while stimulating their projections to prelimbic cortex enhanced safe decision-making. Anticipatory norepinephrine in prelimbic cortex correlated with height avoidance across animals and reflected trial outcome history. Miniscope calcium imaging revealed prelimbic neurons tracked progress in the task. At the population level, experience induced improvements in the decoding of position which correlated strongly with behavioral improvements. With experience, neural trajectories became less variable during the task and reliability of representations correlated with behavioral improvement. Together these results reveal that innate threat experience can induce prefrontal cortical refinement without externally imposed reinforcement. Innate behavioral preference is thus maintained while the neural processes underlying it evolve, suggesting flexibility in neural circuits for interacting with hardwired environmental motivations.

neuroscience↗

bioRxiv2025

Directed cell-type recruitment during consolidation of a remote memory

Memories are consolidated into a distributed neocortical network for long-term storage. Long-term memory retrieval relies on cells that are active during learning and undergo necessary plasticity. However, remote memory retrieval activates a broader circuit, with learning-activated cells representing only a small subset. What are the rules and cell-types governing memory trace reorganization? We identified a class of prefrontal projection neurons that are gradually recruited to a memory trace through synaptic activity of learning-activated cells. This population, which projects to the temporal association area (TEa), progressively strengthens its encoding of memory-induced behaviors, mirroring increases in TEa activity. Notably, the prefrontal-TEa pathway is required for remote but not recent memory retrieval. Our findings reveal a cell type-specific mechanism underlying memory trace reorganization during consolidation.

neuroscience↗

bioRxiv2023

Frontal cortex norepinephrine, serotonin, and dopamine dynamics in an innate fear-reward behavioral model

Animals must survive by foraging for food in an uncertain and dangerous world. Neural circuits for naturalistic decision-making under these conditions must balance competing motivational demands for approaching reward and avoiding danger. To enable flexible switching between motivational states, neuromodulators are released and alter neural excitability and plasticity. The question of how neuromodulators encode motivational state is thus fundamental to systems neuroscience, yet the dynamics of neuromodulators during naturalistic decision making are not fully understood. Here, we developed a naturalistic approach/avoidance task in mice involving a tradeoff between seeking reward versus safety in the presence of looming predation risk. We utilized fiber photometry, computational behavior tracking, and local pharmacology in this task. Silencing medial prefrontal cortex (mPFC) reduced looming defensive behaviors. Moreover, by using fiber photometry combined with GPCR-based sensors, we found that cortical norepinephrine (NE) plays a more prominent role in encoding looming threats while dopamine (DA) represents reward and threat. In contrast, serotonin (5HT) dynamic negatively correlates to both emotional valences. To begin to understand neuromodulatory interactions, we used ex vivo slice physiology to understand 5HT impact on spontaneous firing of locus coeruleus NE neurons. In conclusion, monoamines such as NE, DA, 5HT can converge in their encoding of naturalistic motivated behaviors as well as dissociate from one another. By utilizing this novel innate reward-threat task, we can better understand neurochemical signaling events during natural behavior, and may contribute to the understanding of neural mechanisms underlying emotional decision-making and its implications for psychiatric disorders.

neuroscience↗

bioRxiv2022

Prefrontal norepinephrine represents a threat prediction error under uncertainty

Animals must learn to predict varying threats in the environment to survive by enacting defensive behaviors. Dopamine is involved in the prediction of rewards, encoding a reward prediction error in a similar manner to temporal difference learning algorithm. However, the corresponding molecular and computational form of threat prediction errors is not as well-characterized, although norepinephrine and other neuromodulators and neuropeptides participate in fear learning. Here, we utilized fluorescent norepinephrine recordings over the course of fear learning in concert with reinforcement learning modeling to identify its role in the prediction of threat. By varying timing and sensory uncertainty in the formation of threat associations, we were able to define a precise computational role for norepinephrine in this process. Norepinephrine release approximates the strength of fear associations, and its temporal dynamics are compatible with a prediction error signal. Intriguingly, the release of norepinephrine is influenced by time and sensory feedback, serving as an antithesis of the classical reward prediction error role of dopamine. Thus, these results directly demonstrate a combined cognitive and affective role of norepinephrine in the prediction of threat, with implications for neuropsychiatric disorders such as anxiety and PTSD.

neuroscience↗

bioRxiv2018

Human Puf-A, a Novel Component of 90S Pre-ribosome, Links Ribosome Biogenesis to Cancer Progression

We describe a novel biogenesis factor of the 90S pre-ribosome, Puf-A, which is a negative transcriptional target of p53. The expression of Puf-A is not only upregulated in advanced human lung cancer and tumors of patients especially with TP53 mutation, but also is highly prognostic for stage I lung cancer. Loss of Puf-A expression prevents KrasG12D/p53-/--induced tumor progression in the lungs and induces apoptosis in TP53- mutated cancers and c-Myc/p53-/--transformed cells as well. Overexpression of Puf-A enhances proliferation of normal cells after c-Myc induction and overcomes the cell-cycle checkpoints incurred by p53 expression. Mechanistically, Puf-A interacts with double-stranded structures of the 5.8S sequence within pre-rRNA and maintains the integrity of 90S pre-ribosomes, thereby impacting early ribosome assembly and export of ribosomes from nuclei. Silencing of Puf-A disrupts the assembly of 90S pre-ribosomes and induces the translocation of its associated nucleophosmin (NPM1) from nucleoli to the nucleoplasm, resulting in impairment of ribosome synthesis. Thus, Puf-A is crucial for over-activation of ribosome biogenesis and contributes to tumor progression and cancer growth.

cancer biology↗