Localized inhibition in the Drosophila mushroom body

Abstract

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.

Shore crabs reveal novel evolutionary attributes of the mushroom body

“…These provide dense systems of minute processes, the dispositions of which would allow synaptic contact with every neuronal process supplying a microglomerulus. Accepting that varunid intrinsic neurons correspond to insect Kenyon cells, these GAD-immunoreactive systems suggest correspondence with wide-field anaxonal inhibitory neurons that extend throughout the Drosophila calyx (‘APL neurons’: Liu and Davis, 2009 ; Amin et al, 2020 ). Consequently, such putatively inhibitory anaxonal neurons in the crab suggest a global role in local synaptic inhibition at microglomeruli.…”

Response competition between neurons and antineurons in the mushroom body

“…18,32,44,45 APL forms reciprocal synapses with KCs throughout the mushroom body 18,32 and delivers local, KC division-or compartment-restricted inhibition. [44][45][46] The subthreshold nature of the integration process, 10 however, poses a conundrum: if on and off ab c KCs accumulate sensory evidence by integrating synaptic potentials to spike threshold, 10 how can APL exert inhibitory feedback when neither competitor emits an action potential before the race is decided? A likely answer lies in the peculiar structure and biophysics of the feedback loop.…”

“…18 Here, both neuronal partners form numerous presynaptic active zones, 32,47 indicative of bidirectional communication between them: each ab c KC excites APL through an average of 13.4 synapses-that is, roughly one contact per 20 mm of dendrite-and is inhibited by APL via 10.0 reciprocal synapses. 46 Like its locust analog, the giant GABAergic neuron (GGN), APL is a non-spiking cell whose rate of GABA release tracks local voltage changes in a graded fashion; 48 in GGN and other non-spiking interneurons, depolarizations of 2-5 mV suffice to trigger secretion. 48,49 But how is transmission at the dendritic release sites 32,47 of ab c KCs controlled?…”

Shore crabs reveal novel evolutionary attributes of the mushroom body

“…These provide dense systems of minute processes, the dispositions of which would allow synaptic contact with every neuronal process supplying a microglomerus. Accepting that varunid intrinsic neurons correspond to insect Kenyon cells, these GAD-immunoreactive systems suggest correspondence with wide-field anaxonal inhibitory neurons that extend throughout the Drosophila calyx (‘APL neurons’: Liu and Davis, 2009; Amin et al, 2020). Consequently, such putatively inhibitory anaxonal neurons in the crab suggest a global role in local synaptic inhibition at microglomeruli.…”