A lineage-related reciprocal inhibition circuitry for sensory-motor action selection

Abstract

The insect central complex and vertebrate basal ganglia are forebrain centres involved in selection and maintenance of behavioural actions. However, little is known about the formation of the underlying circuits, or how they integrate sensory information for motor actions. Here, we show that paired embryonic neuroblasts generate central complex ring neurons that mediate sensory-motor transformation and action selection in Drosophila. Lineage analysis resolves four ring neuron subtypes, R1-R4, that form GABAergic inhibition circuitry among inhibitory sister cells. Genetic manipulations, together with functional imaging, demonstrate subtype-specific R neurons mediate the selection and maintenance of behavioural activity. A computational model substantiates genetic and behavioural observations suggesting that R neuron circuitry functions as salience detector using competitive inhibition to amplify, maintain or switch between activity states. The resultant gating mechanism translates facilitation, inhibition and disinhibition of behavioural activity as R neuron functions into selection of motor actions and their organisation into action sequences.

In vivo expansion of functionally integrated GABA ergic interneurons by targeted increase in neural progenitors

“…To further confine Pros attenuation, we restricted GAL4 activity to the head by employing teashirt (tsh)‐GAL80 (Clyne & Miesenbock, ; Fig EV6) and video‐tracked open‐field behavior of freely moving animals using the Drosophila Arousal Tracking (DART) system (Faville et al , ). While this assay can report differences in motor behavior upon EB circuit perturbations (preprint: Kottler et al ), analysis of controls and animals with supernumerary R neurons revealed no significant differences (Fig A–D). Together with the observed functional anatomy (Fig ), these data suggest that Pros‐attenuated, supernumerary GABAergic interneurons are physiologically active and integrate into ellipsoid body R neuron circuitry without detriment to sensory‐motor integration and higher motor control.…”

“…Temporal patterning of progenitors defines the identity of their neuronal progeny. We therefore predicted that supernumerary DAL NSCs should generate supernumerary Poxn and GABA‐expressing ellipsoid body R neurons (preprint: Kottler et al ), which upon differentiation would be able to project into the ellipsoid body ring neuropil.…”

“…To this end, we carried out functional imaging using the fluorescent protein calcium sensor GCaMP6f (Chen et al , ; Figs D and E, and EV5, Movies EV3 and EV4). A characteristic feature of GABAergic R neurons is their inhibition by GABA‐A receptor signaling (preprint: Kottler et al ). To investigate whether the supernumerary interneurons were physiologically active, and thus responded to GABAergic inhibition, we applied picrotoxin, a non‐competitive blocker of GABA‐A receptor chloride channels.…”

“…Ellipsoid body R neurons have been implicated in goal‐directed behavior, higher motor control, spatial orientation learning and memory, as well as in attention, arousal, and decision‐making, suggesting that R neurons are involved in the assessment of sensory information for adaptive behavior (Strausfeld & Hirth, ; Fiore et al , ). Indeed, previous studies showed that R neuron dysfunction affects sensory‐motor transformation and higher motor control (Fiore et al , ; preprint: Kottler et al ).…”

In silico Interrogation of Insect Central Complex Suggests Computational Roles for the Ellipsoid Body in Spatial Navigation

“…Finally, the strength of connectivity can be modulated by dopamine-related learning processes (Waddell, 2013 ), so that the EB effectively integrates current and previous information about all its incoming sensory inputs. In turn, the EB processes its incoming input to release the inhibition of appropriate premotor programs in the LAL, selecting actions in response to the computed sensory stimuli (Fiore et al, 2015 ; Kottler et al, 2017 ).…”