The Organization of Projections from Olfactory Glomeruli onto Higher-Order Neurons

June 8, 2018

Jeanne JM, Fişek M, Wilson RI

Each odorant receptor corresponds to a unique glomerulus in the brain. Projections from different glomeruli then converge in higher brain regions, but we do not understand the logic governing which glomeruli converge and which do not. Here, we use two-photon optogenetics to map glomerular connections onto neurons in the lateral horn, the region of the Drosophila brain that receives the majority of olfactory projections. We identify 39 morphological types of lateral horn neurons (LHNs) and show that different types receive input from different combinations of glomeruli. We find that different LHN types do not have independent inputs; rather, certain combinations of glomeruli converge onto many of the same LHNs and so are over-represented. Notably, many over-represented combinations are composed of glomeruli that prefer chemically dissimilar ligands whose co-occurrence indicates a behaviorally relevant "odor scene." The pattern of glomerulus-LHN connections thus represents a prediction of what ligand combinations will be most salient.


A Brain-wide Circuit Model of Heat-Evoked Swimming Behavior in Larval Zebrafish

May 1, 2018

Haesemeyer M, Robson DN, Li JM, Schier AF, Engert F

Thermosensation provides crucial information, but how temperature representation is transformed from sensation to behavior is poorly understood. Here, we report a preparation that allows control of heat delivery to zebrafish larvae while monitoring motor output and imaging whole-brain calcium signals, thereby uncovering algorithmic and computational rules that couple dynamics of heat modulation, neural activity and swimming behavior. This approach identifies a critical step in the transformation of temperature representation between the sensory trigeminal ganglia and the hindbrain: A simple sustained trigeminal stimulus representation is transformed into a representation of absolute temperature as well as temperature changes in the hindbrain that explains the observed motor output. An activity constrained dynamic circuit model captures the most prominent aspects of these sensori-motor transformations and predicts both behavior and neural activity in response to novel heat stimuli. These findings provide the first algorithmic description of heat processing from sensory input to behavioral output.


Congratulations to Sam Gershman

February 15, 2018
Sloan Fellows

Cholinergic Sensorimotor Integration Regulates Olfactory Steering.

December 21, 2017

Liu H, Yang W, Wu T, Duan F, Soucy E, Jin X, Zhang Y

Sensorimotor integration regulates goal-directed movements. We study the signaling mechanisms underlying sensorimotor integration in C. elegans during olfactory steering, when the sinusoidal movements of the worm generate an in-phase oscillation in the concentration of the sampled odorant. We show that cholinergic neurotransmission encodes the oscillatory sensory response and the motor state of head undulations by acting through an acetylcholine-gated channel and a muscarinic acetylcholine receptor, respectively. These signals converge on two axonal domains of an interneuron RIA, where the sensory-evoked signal suppresses the motor-encoding signal to transform the spatial information of the odorant into the asymmetry between the axonal activities. The asymmetric synaptic outputs of the RIA axonal domains generate a directional bias in the locomotory trajectory. Experience alters the sensorimotor integration to generate specific behavioral changes. Our study reveals how cholinergic neurotransmission, which can represent sensory and motor information in the mammalian brain, regulates sensorimotor integration during goal-directed locomotions.


Cellular and Molecular Analysis of Dendritic Morphogenesis in a Retinal Cell Type That Senses Color Contrast and Ventral Motion.

December 13, 2017

Liu J, Sanes JR

As neuronal dendrites develop, they acquire cell-type-specific features including characteristic size, shape, arborization, location and synaptic patterns. These features, in turn, are major determinants of type-specific neuronal function. Because neuronal diversity complicates the task of relating developmental programs to adult structure and function, we analyzed dendritic morphogenesis in a single retinal ganglion cell (RGC) type in mouse called J-RGC. We documented the emergence of five dendritic features that underlie J-RGC physiology: (1) dendritic field size, which approximate receptive field size; (2) dendritic complexity, which affects how J-RGCs sample space; (3) asymmetry, which contributes to direction-selectivity; (4) restricted lamination within the inner plexiform layer (IPL), which renders J-RGCs responsive to light decrements; and (5) distribution of synaptic inputs, which generate a color-opponent receptive field. We found dendritic growth in J-RGCs is accompanied by a refinement in dendritic self-crossing. Asymmetry arises by a combination of selective pruning and elaboration, whereas laminar restriction results from biased outgrowth toward the outermost IPL. Interestingly, asymmetry develops in a protracted dorsoventral wave, whereas lamination does so in a rapid centrifugal wave. As arbors mature, they acquire excitatory and inhibitory synapses, with the latter forming first and being concentrated in proximal dendrites. Thus, distinct mechanisms operate in different spatiotemporal dimensions of J-RGC dendritic patterning to generate the substrate for specific patterns of synaptogenesis. Finally, we asked whether the defining molecular signature of J-RGCs, the adhesion molecule JAM-B, regulates morphogenesis, and showed that it promotes dendro-dendritic interactions. Our results reveal multiple mechanisms that shape a dendritic arbor.SIGNIFICANCE STATEMENT Visual perception begins in the retina, where distinct types of retinal ganglion cells (RGCs) are tuned to specific visual features such as direction of motion. The features to which each RGC type responds are determined largely by the number and type of synaptic inputs it receives, and these, in turn, are greatly influenced by the size, shape, arborization pattern, and location of its dendrites. We analyzed dendritic morphogenesis in a functionally characterized RGC type, the J-RGC, demonstrating distinct mechanisms that operate in different dimensions to generate the dendritic scaffold and synaptic patterns for feature detection. Our work elucidates cellular and molecular mechanisms that shape dendritic arbors and synaptic distribution, enabling J-RGC connectivity and thus, function.