Parallel visual pathways with topographic versus non-topographic organization connect the Drosophila eyes to the central brain

SummaryOne hallmark of the visual system is the strict retinotopic organization from the periphery towards the central brain, spanning multiple layers of synaptic integration. Recent Drosophila studies on the computation of distinct visual features have shown that retinotopic representation is often lost beyond the optic lobes, due to convergence of columnar neuron types onto optic glomeruli. Nevertheless, functional imaging revealed a spatially accurate representation of visual cues in the central complex (CX), raising the question how this is implemented on a circuit level. By characterizing the afferents to a specific visual glomerulus, the anterior optic tubercle (AOTU), we discovered a spatial segregation of topographic versus non-topographic projections from molecularly distinct classes of medulla projection neurons (medullo-tubercular, or MeTu neurons). Distinct classes of topographic versus non-topographic MeTus form parallel channels, terminating in separate AOTU domains. Both types then synapse onto separate matching topographic fields of tubercular-bulbar (TuBu) neurons which relay visual information towards the dendritic fields of central complex ring neurons in the bulb neuropil, where distinct bulb sectors correspond to a distinct ring domain in the ellipsoid body. Hence, peripheral topography is maintained due to stereotypic circuitry within each TuBu class, providing the structural basis for spatial representation of visual information in the central complex. Together with previous data showing rough topography of lobula projections to a different AOTU subunit, our results further highlight the AOTUs role as a prominent relay station for spatial information from the retina to the central brain.

Antagonistic regulation by insulin-like peptide and activin ensures the elaboration of appropriate dendritic field sizes of amacrine neurons

Establishing appropriate sizes and shapes of dendritic arbors is critical for proper wiring of the central nervous system. Here we report that Insulin-like Peptide 2 (DILP2) locally activates transiently expressed insulin receptors in the central dendrites of Drosophila Dm8 amacrine neurons to positively regulate dendritic field elaboration. We found DILP2 was expressed in L5 lamina neurons, which have axonal terminals abutting Dm8 dendrites. Proper Dm8 dendrite morphogenesis and synapse formation required insulin signaling through TOR (target of rapamycin) and SREBP (sterol regulatory element-binding protein), acting in parallel with previously identified negative regulation by Activin signaling to provide robust control of Dm8 dendrite elaboration. A simulation of dendritic growth revealed trade-offs between dendritic field size and robustness when branching and terminating kinetic parameters were constant, but dynamic modulation of the parameters could mitigate these trade-offs. We suggest that antagonistic DILP2 and Activin signals from different afferents appropriately size Dm8 dendritic fields.

DSCAM-mediated control of dendritic and axonal arbor outgrowth enforces tiling and inhibits synaptic plasticity

Mature mammalian neurons have a limited ability to extend neurites and make new synaptic connections, but the mechanisms that inhibit such plasticity remain poorly understood. Here, we report that OFF-type retinal bipolar cells in mice are an exception to this rule, as they form new anatomical connections within their tiled dendritic fields well after retinal maturity. The Down syndrome cell-adhesion molecule (Dscam) confines these anatomical rearrangements within the normal tiled fields, as conditional deletion of the gene permits extension of dendrite and axon arbors beyond these borders. Dscam deletion in the mature retina results in expanded dendritic fields and increased cone photoreceptor contacts, demonstrating that DSCAM actively inhibits circuit-level plasticity. Electrophysiological recordings from Dscam−/− OFF bipolar cells showed enlarged visual receptive fields, demonstrating that expanded dendritic territories comprise functional synapses. Our results identify cell-adhesion molecule-mediated inhibition as a regulator of circuit-level neuronal plasticity in the adult retina.

A topographic visual pathway into the central brain of Drosophila

SummaryThe visual system is characterized by a strict topographic organization from the retina towards multiple layers of synaptic integration. Recent studies in Drosophila have shown that in the transition from the optic lobes to the central brain, due to convergence of columnar neurons onto optic glomeruli, distinct synaptic units employed in the computation of different visual features, the retinotopic representation is lost in these circuits. However, functional imaging revealed a spatial representation of visual cues in the Drosophila central complex, raising the question about the underlying circuitry, which bypasses optic glomerulus convergence.While characterizing afferent arborizations within Drosophila visual glomeruli, we discovered a spatial segregation of topographic and non-topographic projections from distinct molecular classes of medulla projection neurons, medullo-tubercular (MeTu) neurons, into a specific central brain glomerulus, the anterior optic tubercle (AOTu). Single cell analysis revealed that topographic information is organized by ensembles of MeTu neurons (type 1), forming parallel channels within the AOTu, while a separate class of MeTu neurons (type 2) displays convergent projection, associated with a loss of spatial resolution. MeTu afferents in the AOTu synapse onto a matching topographic field of output projection neurons, these tubercular-bulbar (TuBu) neurons relay visual information towards dendritic fields of central complex ring neurons in the bulb neuropil. Within the bulb, neuronal proximity of the topographic AOTu map as well as channel identity is maintained despite the absence of a stereotyped map organization, providing the structural basis for spatial representation of visual information in the central complex (CX). TuBu neurons project onto dendritic fields of efferent ring neurons, where distinct sectors of the bulb correspond to a distinct ring domain in the ellipsoid body. We found a stereotypic circuitry for each analyzed TuBu class, thus the individual channels of peripheral topography are maintained in the central complex structure. Together with previous data showing rough topography within the lobula AOTu domain, our results on the organization of medulla projection neurons define the AOTu neuropil as the main relay station for spatial information from the optic lobes into the central brain.

The unfolded protein response is required for dendrite morphogenesis

Precise patterning of dendritic fields is essential for the formation and function of neuronal circuits. During development, dendrites acquire their morphology by exuberant branching. How neurons cope with the increased load of protein production required for this rapid growth is poorly understood. Here we show that the physiological unfolded protein response (UPR) is induced in the highly branched Caenorhabditis elegans sensory neuron PVD during dendrite morphogenesis. Perturbation of the IRE1 arm of the UPR pathway causes loss of dendritic branches, a phenotype that can be rescued by overexpression of the ER chaperone HSP-4 (a homolog of mammalian BiP/ grp78). Surprisingly, a single transmembrane leucine-rich repeat protein, DMA-1, plays a major role in the induction of the UPR and the dendritic phenotype in the UPR mutants. These findings reveal a significant role for the physiological UPR in the maintenance of ER homeostasis during morphogenesis of large dendritic arbors.