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  1. Free, publicly-accessible full text available February 1, 2023
  2. Morrison, Abigail (Ed.)
    The Drosophila mushroom body exhibits dopamine dependent synaptic plasticity that underlies the acquisition of associative memories. Recordings of dopamine neurons in this system have identified signals related to external reinforcement such as reward and punishment. However, other factors including locomotion, novelty, reward expectation, and internal state have also recently been shown to modulate dopamine neurons. This heterogeneity is at odds with typical modeling approaches in which these neurons are assumed to encode a global, scalar error signal. How is dopamine dependent plasticity coordinated in the presence of such heterogeneity? We develop a modeling approach that infers a pattern of dopaminemore »activity sufficient to solve defined behavioral tasks, given architectural constraints informed by knowledge of mushroom body circuitry. Model dopamine neurons exhibit diverse tuning to task parameters while nonetheless producing coherent learned behaviors. Notably, reward prediction error emerges as a mode of population activity distributed across these neurons. Our results provide a mechanistic framework that accounts for the heterogeneity of dopamine activity during learning and behavior.« less
  3. Free, publicly-accessible full text available August 25, 2022
  4. Free, publicly-accessible full text available November 1, 2022
  5. Quantum states of light can enable sensing configurations with sensitivities beyond the shot-noise limit (SNL). In order to better take advantage of available quantum resources and obtain the maximum possible sensitivity, it is necessary to determine fundamental sensitivity limits for different possible configurations for a given sensing system. Here, due to their wide applicability, we focus on optical resonance sensors, which detect a change in a parameter of interest through a resonance shift. We compare their fundamental sensitivity limits set by the quantum Cramér-Rao bound (QCRB) based on the estimation of changes in transmission or phase of a probing brightmore »two-mode squeezed state (bTMSS) of light. We show that the fundamental sensitivity results from an interplay between the QCRB and the transfer function of the system. As a result, for a resonance sensor with a Lorentzian lineshape a phase-based scheme outperforms a transmission-based one for most of the parameter space; however, this is not the case for lineshapes with steeper slopes, such as higher order Butterworth lineshapes. Furthermore, such an interplay results in conditions under which the phase-based scheme provides a higher sensitivity but a smaller degree of quantum enhancement than the transmission-based scheme. We also study the effect of losses external to the sensor on the degree of quantum enhancement and show that for certain conditions, probing with a classical state can provide a higher sensitivity than probing with a bTMSS. Finally, we discuss detection schemes, namely optimized intensity-difference and optimized homodyne detection, that can achieve the fundamental sensitivity limits even in the presence of external losses.« less
  6. The mechanisms specifying neuronal diversity are well characterized, yet it remains unclear how or if these mechanisms regulate neural circuit assembly. To address this, we mapped the developmental origin of 160 interneurons from seven bilateral neural progenitors (neuroblasts) and identify them in a synapse-scale TEM reconstruction of the Drosophila larval central nervous system. We find that lineages concurrently build the sensory and motor neuropils by generating sensory and motor hemilineages in a Notch-dependent manner. Neurons in a hemilineage share common synaptic targeting within the neuropil, which is further refined based on neuronal temporal identity. Connectome analysis shows that hemilineage-temporal cohortsmore »share common connectivity. Finally, we show that proximity alone cannot explain the observed connectivity structure, suggesting hemilineage/temporal identity confers an added layer of specificity. Thus, we demonstrate that the mechanisms specifying neuronal diversity also govern circuit formation and function, and that these principles are broadly applicable throughout the nervous system.« less
  7. Animals generate diverse motor behaviors, yet how the same motor neurons (MNs) generate two distinct or antagonistic behaviors remains an open question. Here, we characterize Drosophila larval muscle activity patterns and premotor/motor circuits to understand how they generate forward and backward locomotion. We show that all body wall MNs are activated during both behaviors, but a subset of MNs change recruitment timing for each behavior. We used TEM to reconstruct a full segment of all 60 MNs and 236 premotor neurons (PMNs), including differentially-recruited MNs. Analysis of this comprehensive connectome identified PMN-MN ‘labeled line’ connectivity; PMN-MN combinatorial connectivity; asymmetric neuronalmore »morphology; and PMN-MN circuit motifs that could all contribute to generating distinct behaviors. We generated a recurrent network model that reproduced the observed behaviors, and used functional optogenetics to validate selected model predictions. This PMN-MN connectome will provide a foundation for analyzing the full suite of larval behaviors.« less