Inhibitory muscarinic acetylcholine receptors enhance aversive olfactory learning in adult Drosophila

Innate behaviours, although robust and hard wired, rely on modulation of neuronal circuits, for eliciting an appropriate response according to internal states and external cues. Drosophila flight is one such innate behaviour that is modulated by intracellular calcium release through inositol 1,4,5-trisphosphate receptors (IP3Rs). Cellular mechanism(s) by which IP3Rs modulate neuronal function for specific behaviours remain speculative, in vertebrates and invertebrates. To address this, we generated an inducible dominant negative form of the IP3R (IP3RDN). Flies with neuronal expression of IP3RDN exhibit flight deficits. Expression of IP3RDN helped identify key flight-modulating dopaminergic neurons with axonal projections in the mushroom body. Flies with attenuated IP3Rs in these presynaptic dopaminergic neurons exhibit shortened flight bouts and a disinterest in seeking food, accompanied by reduced excitability and dopamine release upon cholinergic stimulation. Our findings suggest that the same neural circuit modulates the drive for food search and for undertaking longer flight bouts.

Section: Resultsmentioning

confidence: 99%

Modulation of flight and feeding behaviours requires presynaptic IP3Rs in dopaminergic neurons

Sharma

Hasan

2020

“…Motion correction was carried out as in Bielopolski et al, 2019 ; Lin et al, 2014 ; flies with excessive uncorrectable motion were discarded. For experiments without 3D-skeletonization (see below), ΔF/F was calculated in ImageJ for manually drawn regions of interest (ROIs).…”

Section: Methodsmentioning

confidence: 99%

Localized inhibition in the Drosophila mushroom body

Amin

Apostolopoulou

Suárez-Grimalt

et al. 2020

Self 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.

“…Glutamate for instance is mainly excitatory, however, in invertebrates it can also have inhibitory effects when it acts on a glutamate-gated chloride channel, known as GluClα ( Cully et al, 1996 ; Liu and Wilson, 2013 ; Mauss et al, 2015 ). Recently, it has also been shown that acetylcholine, usually excitatory, might also be inhibitory in Drosophila , if it binds to the muscarinic mAChR-A receptor ( Bielopolski et al, 2019 ). Hence, knowledge inferring the type of transmitter receptor at a synapse is essential for our understanding of the way neural circuits process information.…”

Section: Introductionmentioning

confidence: 99%

Conditional protein tagging methods reveal highly specific subcellular distribution of ion channels in motion-sensing neurons

Fendl

Vieira

Borst

2020

Neurotransmitter receptors and ion channels shape the biophysical properties of neurons, from the sign of the response mediated by neurotransmitter receptors to the dynamics shaped by voltage-gated ion channels. Therefore, knowing the localizations and types of receptors and channels present in neurons is fundamental to our understanding of neural computation. Here, we developed two approaches to visualize the subcellular localization of specific proteins in Drosophila: The flippase-dependent expression of GFP-tagged receptor subunits in single neurons and 'FlpTag', a versatile new tool for the conditional labelling of endogenous proteins. Using these methods, we investigated the subcellular distribution of the receptors GluClα, Rdl, and Dα7 and the ion channels para and Ih in motion-sensing T4/T5 neurons of the Drosophila visual system. We discovered a strictly segregated subcellular distribution of these proteins and a sequential spatial arrangement of glutamate, acetylcholine, and GABA receptors along the dendrite that matched the previously reported EM-reconstructed synapse distributions.