@article {67793, title = {Circuits for integrating learned and innate valences in the insect brain.}, journal = {eLife}, volume = {10}, year = {2021}, month = {2021 Nov 10}, abstract = {

Animal behavior is shaped both by evolution and by individual experience. Parallel brain pathways encode innate and learned valences of cues, but the way in which they are integrated during action-selection is not well understood. We used electron microscopy to comprehensively map with synaptic resolution all neurons downstream of all Mushroom Body output neurons (encoding learned valences) and characterized their patterns of interaction with Lateral Horn neurons (encoding innate valences) in larva. The connectome revealed multiple types that receive convergent Mushroom Body and Lateral Horn inputs. A subset of these receives excitatory input from positive-valence MB and LH pathways and inhibitory input from negative-valence MB pathways. We confirmed functional connectivity from LH and MB pathways and behavioral roles of two of these neurons. These neurons encode integrated odor value and bidirectionally regulate turning. Based on this we speculate that learning could potentially skew the balance of excitation and inhibition onto these neurons and thereby modulate turning. Together, our study provides insights into the circuits that integrate learned and innate valences to modify behavior.

}, issn = {2050-084X}, doi = {10.7554/eLife.62567}, author = {Eschbach, Claire and Fushiki, Akira and Winding, Michael and Afonso, Bruno and Andrade, Ingrid V and Cocanougher, Benjamin T and Eichler, Katharina and Gepner, Ruben and Si, Guangwei and Valdes-Aleman, Javier and Fetter, Richard D and Gershow, Marc and Jefferis, Gregory Sxe and Samuel, Aravinthan Dt and Truman, James W and Cardona, Albert and Zlatic, Marta} } @article {65860, title = {Central processing of leg proprioception in Drosophila.}, journal = {eLife}, volume = {9}, year = {2020}, month = {2020 Dec 02}, abstract = {

Proprioception, the sense of self-movement and position, is mediated by mechanosensory neurons that detect diverse features of body kinematics. Although proprioceptive feedback is crucial for accurate motor control, little is known about how downstream circuits transform limb sensory information to guide motor output. Here, we investigate neural circuits in that process proprioceptive information from the fly leg. We identify three cell-types from distinct developmental lineages that are positioned to receive input from proprioceptor subtypes encoding tibia position, movement, and vibration. 13Bα neurons encode femur-tibia joint angle and mediate postural changes in tibia position. 9Aα neurons also drive changes in leg posture, but encode a combination of directional movement, high frequency vibration, and joint angle. Activating 10Bα neurons, which encode tibia vibration at specific joint angles, elicits pausing in walking flies. Altogether, our results reveal that central circuits integrate information across proprioceptor subtypes to construct complex sensorimotor representations that mediate diverse behaviors, including reflexive control of limb posture and detection of leg vibration.

}, issn = {2050-084X}, doi = {10.7554/eLife.60299}, author = {Agrawal, Sweta and Dickinson, Evyn S and Sustar, Anne and Gurung, Pralaksha and Shepherd, David and Truman, James W and Tuthill, John C} } @article {49583, title = {Convergence of monosynaptic and polysynaptic sensory paths onto common motor outputs in a feeding connectome.}, journal = {eLife}, volume = {7}, year = {2018}, month = {2018 Dec 11}, abstract = {

We reconstructed, from a whole CNS EM volume, the synaptic map of input and output neurons that underlie food intake behavior of larvae. Input neurons originate from enteric, pharyngeal and external sensory organs and converge onto seven distinct sensory synaptic compartments within the CNS. Output neurons consist of feeding motor, serotonergic modulatory and neuroendocrine neurons. Monosynaptic connections from a set of sensory synaptic compartments cover the motor, modulatory and neuroendocrine targets in overlapping domains. Polysynaptic routes are superimposed on top of monosynaptic connections, resulting in divergent sensory paths that converge on common outputs. A completely different set of sensory compartments is connected to the mushroom body calyx. The mushroom body output neurons are connected to interneurons that directly target the feeding output neurons. Our results illustrate a circuit architecture in which monosynaptic and multisynaptic connections from sensory inputs traverse onto output neurons via a series of converging paths.

}, issn = {2050-084X}, doi = {10.7554/eLife.40247}, author = {Miroschnikow, Anton and Schlegel, Philipp and Schoofs, Andreas and Hueckesfeld, Sebastian and Li, Feng and Schneider-Mizell, Casey M and Fetter, Richard D and Truman, James W and Cardona, Albert and Pankratz, Michael J} } @article {48720, title = {The complete connectome of a learning and memory centre in an insect brain.}, journal = {Nature}, volume = {548}, year = {2017}, month = {2017 Aug 09}, pages = {175-182}, abstract = {

Associating stimuli with positive or negative reinforcement is essential for survival, but a complete wiring diagram of a higher-order circuit supporting associative memory has not been previously available. Here we reconstruct one such circuit at synaptic resolution, the Drosophila larval mushroom body. We find that most Kenyon cells integrate random combinations of inputs but that a subset receives stereotyped inputs from single projection neurons. This organization maximizes performance of a model output neuron on a stimulus discrimination task. We also report a novel canonical circuit in each mushroom body compartment with previously unidentified connections: reciprocal Kenyon cell to modulatory neuron connections, modulatory neuron to output neuron connections, and a surprisingly high number of recurrent connections between Kenyon cells. Stereotyped connections found between output neurons could enhance the selection of learned behaviours. The complete circuit map of the mushroom body should guide future functional studies of this learning and memory centre.

}, issn = {1476-4687}, doi = {10.1038/nature23455}, author = {Eichler, Katharina and Li, Feng and Litwin-Kumar, Ashok and Park, Youngser and Andrade, Ingrid and Schneider-Mizell, Casey M and Saumweber, Timo and Huser, Annina and Eschbach, Claire and Gerber, Bertram and Fetter, Richard D and Truman, James W and Priebe, Carey E and Abbott, L F and Thum, Andreas S and Zlatic, Marta and Cardona, Albert} } @article {47935, title = {Competitive disinhibition mediates behavioral choice and sequences in Drosophila.}, journal = {Cell}, volume = {167}, year = {2016}, month = {2016 Oct 5}, pages = {858-70}, abstract = {

Even a simple sensory stimulus can elicit distinct innate behaviors and sequences. During sensorimotor decisions, competitive interactions among neurons that promote distinct behaviors must ensure the selection and maintenance of one behavior, while suppressing others. The circuit implementation of these competitive interactions is still an open question. By combining comprehensive electron microscopy reconstruction of inhibitory interneuron networks, modeling, electrophysiology, and behavioral studies, we determined the circuit mechanisms that\ contribute to the Drosophila larval sensorimotor decision to startle, explore, or perform a sequence of the two in response to a mechanosensory stimulus. Together, these studies reveal that, early in sensory processing, (1) reciprocally connected feedforward inhibitory interneurons implement behavioral choice, (2) local feedback disinhibition provides positive feedback that consolidates and maintains the chosen behavior, and (3) lateral disinhibition promotes sequence transitions. The combination of these interconnected circuit motifs can implement both behavior selection and the serial organization of behaviors into a sequence.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2016.09.009}, author = {Jovanic, Tihana and Schneider-Mizell, Casey M and Shao, Mei and Masson, Jean-Baptiste and Denisov, Gennady and Fetter, Richard D and Mensh, Brett D and Truman, James W and Cardona, Albert and Zlatic, Marta} } @article {2448, title = {Cellular mechanisms of dendrite pruning in Drosophila: insights from in vivo time-lapse of remodeling dendritic arborizing sensory neurons.}, journal = {Development}, volume = {132}, year = {2005}, month = {2005 Aug}, pages = {3631-42}, abstract = {

Regressive events that refine exuberant or inaccurate connections are critical in neuronal development. We used multi-photon, time-lapse imaging to examine how dendrites of Drosophila dendritic arborizing (da) sensory neurons are eliminated during early metamorphosis, and how intrinsic and extrinsic cellular mechanisms control this deconstruction. Removal of the larval dendritic arbor involves two mechanisms: local degeneration and branch retraction. In local degeneration, major branch severing events entail focal disruption of the microtubule cytoskeleton, followed by thinning of the disrupted region, severing and fragmentation. Retraction was observed at distal tips of branches and in proximal stumps after severing events. The pruning program of da neuron dendrites is steroid induced; cell-autonomous dominant-negative inhibition of steroid action blocks local degeneration, although retraction events still occur. Our data suggest that steroid-induced changes in the epidermis may contribute to dendritic retraction. Finally, we find that phagocytic blood cells not only engulf neuronal debris but also attack and sever intact branches that show signs of destabilization.

}, keywords = {Abdomen, Afferent, Animals, Biological, Cytoskeleton, Dendrites, Drosophila melanogaster, Fluorescent Dyes, Metamorphosis, Microscopy, Neurons, Phagocytes, Receptors, Steroid, Video}, issn = {0950-1991}, doi = {10.1242/dev.01928}, author = {Williams, Darren W and Truman, James W} }