Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics

Aso, Yoshinori; Ray, Robert P.; Long, Xi; Cichewicz, Karol; Ngo, Teri-TB; Sharp, Brandi; Christoforou, Christina; Lemire, Andrew; Hirsh, Jay; Litwin-Kumar, Ashok; Rubin, Gerald M.

doi:10.1101/682815

Cited by 30 publications

(64 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We based these divisions on findings that (1) these regions are innervated by different dopaminergic neurons that respond differentially to ‘punishment’ (e.g. electric shock) vs. ‘reward’ (reviewed in Amin and Lin, 2019 ), (2) dopaminergic neurons release synaptic vesicles onto APL in response to electric shocks ( Zhou et al, 2019 ), and (3) APL expresses the dopamine receptors DopEcR ( Aso et al, 2019 ) and the inhibitory Dop2R ( Zhou et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

“…In addition to reflecting differential synaptic inputs, this spatially localized activity in APL most likely also reflects intrinsic properties of APL’s membrane excitability that prevent activity from spreading. To validate the hypothesis that intrinsic properties could contribute, we analyzed an RNA-seq dataset revealing mRNA levels in the cell bodies of Kenyon cells, dopaminergic neurons, mushroom body output neurons, the dorsal paired medial (DPM) neuron, and APL ( Aso et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Localized inhibition in the Drosophila mushroom body

Amin

Apostolopoulou

Suárez-Grimalt

et al. 2020

eLife

View full text Add to dashboard Cite

Many neurons show compartmentalized activity, in which activity does not spread readily across the cell, allowing input and output to occur locally. However, the functional implications of compartmentalized activity for the wider neural circuit are often unclear. We addressed this problem in the Drosophila mushroom body, whose principal neurons, Kenyon cells, receive feedback inhibition from a non-spiking interneuron called APL. We used local stimulation and volumetric calcium imaging to show that APL inhibits Kenyon cells’ dendrites and axons, and that both activity in APL and APL’s inhibitory effect on Kenyon cells are spatially localized (the latter somewhat less so), allowing APL to differentially inhibit different mushroom body compartments. Applying these results to the Drosophila hemibrain connectome predicts that individual Kenyon cells inhibit themselves via APL more strongly than they inhibit other individual Kenyon cells. These findings reveal how cellular physiology and detailed network anatomy can combine to influence circuit function.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Localized inhibition in the Drosophila mushroom body

Amin

Apostolopoulou

Suárez-Grimalt

et al. 2020

eLife

View full text Add to dashboard Cite

show abstract

“…Next, to determine the signs of the connections between identified partners -that is, whether synaptic connections are excitatory or inhibitory-we performed RNA-Seq on each cell type that we could target specifically with Gal4 driver lines ( Figure 2F-H; see Methods) (Aso et al, 2019;Davis et al, 2019). For cell types that did not yield clear answers or that we could not target cleanly, we also used FISH to determine the likely neurotransmitter (Long et al, 2017;Meissner et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

The neuroanatomical ultrastructure and function of a biological ring attractor

Turner-Evans

Jensen

Ali

et al. 2019

Preprint

Self Cite

105

View full text Add to dashboard Cite

Neural representations of head direction have been discovered in many different species. A large body of theoretical work has proposed that the dynamics associated with these representations might be generated, maintained, and updated by recurrent network structures called ring attractors. Ring attractor models rely on specific assumptions about the structure of excitatory and inhibitory connectivity. These assumptions have been difficult to test directly. We therefore performed electron-microscopy-based circuit reconstruction and RNA profiling of identified cell types in the heading direction system of Drosophila melanogaster to directly examine excitatory and inhibitory synaptic connectivity, generating a dataset that should serve as a reference for future functional studies of the network. Consistent with several theoretical models, we identified network motifs that have been hypothesized to maintain the heading representation in darkness, update it when the animal turns, and tether it to visual cues. Genetically targeted two-photon calcium imaging and thermogenetic perturbation of the constituent neuron types during behavior provided additional support for these functional roles. However, we also discovered network motifs absent in current models, including a surprising degree of recurrence between arbors of different neurons with mixed pre-and post-synaptic specializations. Overall, our results confirm that the Drosophila heading direction network contains the core components of a ring attractor while also revealing unpredicted structural features that might enable the heading system to accurately track the animal's heading with a small number of neurons. Importantly, however, these and other models of attractor networks in the fly have assumed the circuit's connectivity based on relatively indirect evidence (Cope et al., 2017;Han et al., 2019;Kakaria and de Bivort, 2017;Kim et al., 2017;Su et al., 2017;Turner-Evans et al., 2017). For example, the location of pre-and post-synaptic arbors has been inferred from whether neural processes visible in light-microscopic images seem spine-or bouton-like in specific substructures (Hanesch et al., 1989;Lin et al., 2013;Wolff et al., 2015). The hypothesized connectivity of the circuit has then been derived from light-level overlap between the putatively pre-and post-synaptic arbors of neurons . In Drosophila, such conclusions have been bolstered by employing GFP-reconstitution-acrosssynaptic-partners (GRASP) (Xie et al., 2017) and trans-Tango (Omoto et al., 2018) techniques. Although both GRASP and trans-Tango are powerful techniques, their reliability and accuracy when used to estimate pairwise connectivity is limited (Lee et al., 2017; Talay et al., 2017). Similarly, measurements of functional connectivity by optogenetic stimulation of one neuron type and calcium imaging of another (Franconville et al., 2018) cannot conclusively establish the presence or absence of monosynaptic connectivity.In the current study, we established the synaptic-and cellular-resolution str...

show abstract

“…What might be the neuronal subsets that produce NO and regulate period length of locomotor activity? A recent study by the group of Y. Aso and G. Rubin [ 54 ], has shown that NO acts as a co-transmitter in a subset of dopaminergic neurons, specifically in some of the PAMs, PPL1s and PPL2abs. It is thus possible that dopamine signaling modulated by NO is involved in the control of the locomotor activity period.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide mediates neuro-glial interaction that shapes Drosophila circadian behavior

2020

View full text Add to dashboard Cite

Drosophila circadian behavior relies on the network of heterogeneous groups of clock neurons. Short-and long-range signaling within the pacemaker circuit coordinates molecular and neural rhythms of clock neurons to generate coherent behavioral output. The neurochemistry of circadian behavior is complex and remains incompletely understood. Here we demonstrate that the gaseous messenger nitric oxide (NO) is a signaling molecule linking circadian pacemaker to rhythmic locomotor activity. We show that mutants lacking nitric oxide synthase (NOS) have behavioral arrhythmia in constant darkness, although molecular clocks in the main pacemaker neurons are unaffected. Behavioral phenotypes of mutants are due in part to the malformation of neurites of the main pacemaker neurons, s-LNvs. Using cell-type selective and stage-specific gain-and loss-of-function of NOS, we also demonstrate that NO secreted from diverse cellular clusters affect behavioral rhythms. Furthermore, we identify the perineurial glia, one of the two glial subtypes that form the blood-brain barrier, as the major source of NO that regulates circadian locomotor output. These results reveal for the first time the critical role of NO signaling in the Drosophila circadian system and highlight the importance of neuro-glial interaction in the neural circuit output.

show abstract

Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics

Cited by 30 publications

References 119 publications

Localized inhibition in the Drosophila mushroom body

Localized inhibition in the Drosophila mushroom body

The neuroanatomical ultrastructure and function of a biological ring attractor

Nitric oxide mediates neuro-glial interaction that shapes Drosophila circadian behavior

Contact Info

Product

Resources

About