Akira Mamiya, Pralaksha Gurung, Igor Siwanowicz, Anne Sustar, Chenghao Chen, Jasper S Phelps, Aaron T Kuan, Alexandra Pacureanu, Wei-Chung Allen Lee, Natasha Mhatre, and John C. Tuthill. 8/9/2022. “
Biomechanical origins of proprioceptive maps in the Drosophila leg.” bioRxiv.
Publisher's VersionAbstractProprioception, the sense of body position and movement, is essential for effective motor control. Because proprioceptive sensory neurons are embedded in complex and dynamic tissues, it has been challenging to understand how they sense and encode mechanical stimuli. Here, we find that proprioceptor neurons in the Drosophila femur are organized into functional groups that are biomechanically specialized to detect features of tibia joint kinematics. The dendrites of position and vibration-tuned proprioceptors receive distinct mechanical signals via the arculum, an elegant mechanical structure that decomposes movement of the tibia joint into orthogonal components. The cell bodies of position-tuned proprioceptors form a goniotopic map of joint angle, whereas the dendrites of vibration-tuned proprioceptors form a tonotopic map of tibia vibration frequency. Our findings reveal biomechanical mechanisms that underlie proprioceptor feature selectivity and identify common organizational principles between proprioception and other topographically organized sensory systems.
Aaron T Kuan, Giulio Bondanelli, Laura N Driscoll, Julie Han, Minsu Kim, David GC Hildebrand, Brett J Graham, Logan A Thomas, Stefano Panzeri, Christopher D Harvey, and Wei-Chung Allen Lee. 4/14/2022. “
Synaptic wiring motifs in posterior parietal cortex support decision-making.” bioRxiv.
Publisher's VersionAbstractThe posterior parietal cortex (PPC) exhibits choice-selective activity during perceptual decision-making tasks. However, it is not known how this selective activity arises from the underlying synaptic connectivity. Here, we combined virtual reality behavior, two-photon calcium imaging, high throughput electron microscopy, and circuit modeling to analyze how synaptic connectivity between neurons in PPC relates to their selective activity. We found that excitatory pyramidal neurons preferentially target inhibitory interneurons with the same selectivity. In turn, inhibitory interneurons preferentially target pyramidal neurons with opposite selectivity, forming an opponent inhibition motif. Using circuit models, we show that opponent inhibition amplifies selective inputs and induces competition between neural populations with opposite selectivity, thereby improving the encoding of trial-type information. These results provide evidence for how synaptic connectivity in cortical circuits supports a learned decision-making task.
Yajun Xie, Aaron T Kuan, Wengang Wang, Zachary T Herbert, Olivia Mosto, Olubusola Olukoya, Manal Adam, Steve Vu, Minsu Kim, Diana Tran, Nicolás Gómez, Claire Charpentier, Ingie Sorour, Tiara E Lacey, Michael Y Tolstorukov, Bernardo L Sabatini, Wei-Chung Allen Lee, and Corey C Harwell. 2022. “
Astrocyte-neuron crosstalk through Hedgehog signaling mediates cortical synapse development.” Cell Rep, 38, 8, Pp. 110416.
AbstractNeuron-glia interactions play a critical role in the regulation of synapse formation and circuit assembly. Here we demonstrate that canonical Sonic hedgehog (Shh) pathway signaling in cortical astrocytes acts to coordinate layer-specific synaptic connectivity. We show that the Shh receptor Ptch1 is expressed by cortical astrocytes during development and that Shh signaling is necessary and sufficient to promote the expression of genes involved in regulating synaptic development and layer-enriched astrocyte molecular identity. Loss of Shh in layer V neurons reduces astrocyte complexity and coverage by astrocytic processes in tripartite synapses; conversely, cell-autonomous activation of Shh signaling in astrocytes promotes cortical excitatory synapse formation. Furthermore, Shh-dependent genes Lrig1 and Sparc distinctively contribute to astrocyte morphology and synapse formation. Together, these results suggest that Shh secreted from deep-layer cortical neurons acts to specialize the molecular and functional features of astrocytes during development to shape circuit assembly and function.
Tomas Osorno, Stephanie Rudolph, Tri Nguyen, Velina Kozareva, Naeem M Nadaf, Aliya Norton, Evan Z Macosko, Wei-Chung Allen Lee, and Wade G Regehr. 2022. “
Candelabrum cells are ubiquitous cerebellar cortex interneurons with specialized circuit properties.” Nat Neurosci, 25, 6, Pp. 702-713.
AbstractTo understand how the cerebellar cortex transforms mossy fiber (MF) inputs into Purkinje cell (PC) outputs, it is vital to delineate the elements of this circuit. Candelabrum cells (CCs) are enigmatic interneurons of the cerebellar cortex that have been identified based on their morphology, but their electrophysiological properties, synaptic connections and function remain unknown. Here, we clarify these properties using electrophysiology, single-nucleus RNA sequencing, in situ hybridization and serial electron microscopy in mice. We find that CCs are the most abundant PC layer interneuron. They are GABAergic, molecularly distinct and present in all cerebellar lobules. Their high resistance renders CC firing highly sensitive to synaptic inputs. CCs are excited by MFs and granule cells and are strongly inhibited by PCs. CCs in turn primarily inhibit molecular layer interneurons, which leads to PC disinhibition. Thus, inputs, outputs and local signals converge onto CCs to allow them to assume a unique role in controlling cerebellar output.
Tri M Nguyen, Logan A Thomas, Jeff L Rhoades, Ilaria Ricchi, Xintong Cindy Yuan, Arlo Sheridan, David GC Hildebrand, Jan Funke, Wade G Regehr, and Wei-Chung Allen Lee. 2022. “
Structured cerebellar connectivity supports resilient pattern separation.” Nature.
AbstractThe cerebellum is thought to help detect and correct errors between intended and executed commands1,2 and is critical for social behaviours, cognition and emotion3-6. Computations for motor control must be performed quickly to correct errors in real time and should be sensitive to small differences between patterns for fine error correction while being resilient to noise7. Influential theories of cerebellar information processing have largely assumed random network connectivity, which increases the encoding capacity of the network's first layer8-13. However, maximizing encoding capacity reduces the resilience to noise7. To understand how neuronal circuits address this fundamental trade-off, we mapped the feedforward connectivity in the mouse cerebellar cortex using automated large-scale transmission electron microscopy and convolutional neural network-based image segmentation. We found that both the input and output layers of the circuit exhibit redundant and selective connectivity motifs, which contrast with prevailing models. Numerical simulations suggest that these redundant, non-random connectivity motifs increase the resilience to noise at a negligible cost to the overall encoding capacity. This work reveals how neuronal network structure can support a trade-off between encoding capacity and redundancy, unveiling principles of biological network architecture with implications for the design of artificial neural networks.
Jenny Lu, Amir H Behbahani, Lydia Hamburg, Elena A Westeinde, Paul M Dawson, Cheng Lyu, Gaby Maimon, Michael H Dickinson, Shaul Druckmann, and Rachel I Wilson. 2022. “
Transforming representations of movement from body- to world-centric space.” Nature, 601, 7891, Pp. 98-104.
AbstractWhen an animal moves through the world, its brain receives a stream of information about the body's translational velocity from motor commands and sensory feedback signals. These incoming signals are referenced to the body, but ultimately, they must be transformed into world-centric coordinates for navigation1,2. Here we show that this computation occurs in the fan-shaped body in the brain of Drosophila melanogaster. We identify two cell types, PFNd and PFNv3-5, that conjunctively encode translational velocity and heading as a fly walks. In these cells, velocity signals are acquired from locomotor brain regions6 and are multiplied with heading signals from the compass system. PFNd neurons prefer forward-ipsilateral movement, whereas PFNv neurons prefer backward-contralateral movement, and perturbing PFNd neurons disrupts idiothetic path integration in walking flies7. Downstream, PFNd and PFNv neurons converge onto hΔB neurons, with a connectivity pattern that pools together heading and translation direction combinations corresponding to the same movement in world-centric space. This network motif effectively performs a rotation of the brain's representation of body-centric translational velocity according to the current heading direction. Consistent with our predictions, we observe that hΔB neurons form a representation of translational velocity in world-centric coordinates. By integrating this representation over time, it should be possible for the brain to form a working memory of the path travelled through the environment8-10.