Competitive Disinhibition Mediates Behavioral Choice and Sequences in Drosophila

Abstract

Even a simple sensory stimulus can elicit distinct innate behaviors and sequences. During sensorimotor decisions, competitive interactions among neurons that promote distinct behaviors must ensure the selection and maintenance of one behavior, while suppressing others. The circuit implementation of these competitive interactions is still an open question. By combining comprehensive electron microscopy reconstruction of inhibitory interneuron networks, modeling, electrophysiology, and behavioral studies, we determined the circuit mechanisms that contribute to the Drosophila larval sensorimotor decision to startle, explore, or perform a sequence of the two in response to a mechanosensory stimulus. Together, these studies reveal that, early in sensory processing, (1) reciprocally connected feedforward inhibitory interneurons implement behavioral choice, (2) local feedback disinhibition provides positive feedback that consolidates and maintains the chosen behavior, and (3) lateral disinhibition promotes sequence transitions. The combination of these interconnected circuit motifs can implement both behavior selection and the serial organization of behaviors into a sequence.

Serotonergic Modulation Enables Pathway-Specific Plasticity in a Developing Sensory Circuit in Drosophila

“…Sample sizes were estimated based on previous publications in the field (Jovanic et al, 2016; Ohyama et al, 2015; Yao et al, 2012). To reduce possible variation in each batch of fly cultures, samples from more than 3 separate trials, each of which included similar numbers of samples, were analyzed.…”

“…To analyze the activity levels of A08n neurons, Max ΔF/F0 for individual A08n neurons were plotted on the graph and used for statistical analyses (i.e., each dot indicates one A08n). Because the responses of Basin-4 neurons—unlike A08n neurons—are highly variable within each VNC (data not shown) (Jovanic et al, 2016), the average of Max ΔF/F0 of 10 Basin-4 neurons from abdominal segments 3–7 in each VNC were calculated to represent the Basin-4 activity in each VNC.…”

“…Because the responses of Basin-4 neurons are highly variable within each VNC (data not shown) (Jovanic et al, 2016), the average of Max ΔF/F 0 of 10 Basin-4 neurons from abdominal segments 3 to 7 in each VNC were calculated to represent Basin-4 activity in each VNC (i.e., each dot indicates one larva). n = 7 and 6 larvae in “- AITC” and “+ AITC”, respectively.…”

High-content behavioral profiling reveals neuronal genetic network modulating Drosophila larval locomotor program

“…Recent technologies in high-throughput phenotyping have advanced research in this area from a single gene level to a systems level. For example, a multi-larvae tracking system [7], in combination with optogenetics and a vast collection of Gal4 drivers, have enabled discovery of the neuronal circuits regulating behaviors such as peristaltic crawling [8] and decision-making in response to a mechano-stimulus [9]. …”

Pavlovian Conditioning of Larval Drosophila: An Illustrated, Multilingual, Hands-On Manual for Odor-Taste Associative Learning in Maggots

“…Even so, they feature fundamental adult-like circuit motifs (e.g., in the olfactory pathways: Vosshall and Stocker, 2007; Stocker, 2008) and exhibit fundamental faculties of behavior, including learning and memory (see below). Last but not least, a synapse-by-synapse connectome of the larval nervous system seems within reach, and driver strains for transgenic manipulation can now be established to cover the neurons of the larva, one at a time (Li et al, 2014; Ohyama et al, 2015; Berck et al, 2016; Fushiki et al, 2016; Jovanic et al, 2016; Schlegel et al, 2016; Schneider-Mizell et al, 2016; Zwart et al, 2016). Taken together, the possibilities for research into the behavioral neurogenetics of larval Drosophila appear enticing, given the combination of analytical power, ease, elegance, and completeness.…”