A Computational Model of the Escape Response Latency in the Giant Fiber System of Drosophila melanogaster

Abstract

The giant fiber system (GFS) is a multi-component neuronal pathway mediating rapid escape response in the adult fruit-fly Drosophila melanogaster, usually in the face of a threatening visual stimulus. Two branches of the circuit promote the response by stimulating an escape jump followed by flight initiation. A recent work demonstrated an age-associated decline in the speed of signal propagation through the circuit, measured as the stimulus-to-muscle depolarization response latency. The decline is likely due to the diminishing number of inter-neuronal gap junctions in the GFS of ageing flies. In this work, we presented a realistic conductance-based, computational model of the GFS that recapitulates the experimental results and identifies some of the critical anatomical and physiological components governing the circuit's response latency. According to our model, anatomical properties of the GFS neurons have a stronger impact on the transmission than neuronal membrane conductance densities. The model provides testable predictions for the effect of experimental interventions on the circuit's performance in young and ageing flies.

Keywords: Drosophila; aging; computational model; escape response; gap junctions; ion channels.

Figure 1.

Diagram of the GFS anatomy. Two GF interneurons originating in the brain (red) descend to the thoracic ganglia where they connect, via a mixed (electrical and chemical) synapse, to the TTMn (blue) innervating the cylindrical TTM. In the second branch of the circuit, the GFs form a mixed synapse with the PSI (green), which, in turn, chemically synapses onto the DLMns (yellow) innervating the DLMs. Red circles in the brain denote approximate positions of the GF cell bodies.

Figure 2.

GFS model architecture and response latency measurements. A, Model architecture and geometry, showing the cylindrical sections that make up the four cell types in the model (to scale), along with the location of electrical and chemical synapses. Active sections (axons) are shown in dark colors. Bolt denotes the proximal end of the GF that is stimulated in the simulation, and arrows denote the distal ends of the axons, from which the voltage recordings shown in B were taken. The response latency in the DLM pathway is slightly delayed compared to the latency in the (shorter) TTM branch. B, Membrane potential recorded in the model TTMn (blue), DLMn (green), and PSI (orange), for “young fly” g_gap value (135 μS, top) and “old fly” g_gap value (34.5 μS, bottom). C, Latency from stimulus onset to muscle response as predicted by the model for TTM (blue) and DLM (green), as a function of g_gap. The latency values recorded experimentally are indicated by dashed lines, and the g_gap values where they coincide with the values predicted by the model are shown by magenta and red bars (for young and old flies, respectively).

Figure 3.

Co-dependency of the response latency on g_gap. A–C, top, The latency landscape in the TTM, shown using iso-latency lines (labeled with response latency values in milliseconds) as a function of the global gap junction conductance (g_gap) and maximal transient voltage-gated sodium conductance (ḡ_Nat, A), maximal voltage-gated potassium conductance (ḡ_K, B), and leak conductance (ḡ_leak, C). Blue and orange dots represent the values for young and old flies, respectively. The region in the landscape representing young fly latency is marked by red dashed lines. Bottom, Cross sections in the latency landscape, showing the change in latency (relative to experimentally measured values) as a function of the three conductance types, for young flies (blue) and old flies (orange). D–F, same as A–C, for the DLM.

Figure 4.

Impact of anatomic model parameters on response latency. A–D, TTM Latency as a function of g_gap and anatomic parameters in the TTM branch of the model: the diameter of TTMn sections (A), and the length of the TTMn lateral dendrite (B), medial dendrite (C), and axon (D). E–H, DLM latency as a function of g_gap and anatomic parameters in the DLM branch of the model: PSI section diameter (E), PSI dendrite length (F), DLMn dendrite length (G), and DLMn axon length (H).

Figure 5.

Co-dependency of the response latency on different parameter combinations. A, TTM latency as a function of maximal voltage-gated transient sodium conductance (ḡ_Nat) and maximal voltage-gated potassium conductance (ḡ_K). B, TTM latency as a function of sodium reversal potential (E_Na) and potassium reversal potential (E_K). C, TTM latency as a function of the TTMn medial dendrite length and TTM lateral dendrite length. D, DLM latency as a function of the PSI-to-DLMn chemical synapse weight, and the synapse location along the DLMn dendrite. E, GF latency as a function of the GF diameter and length. Blue dots represent the values for young and old flies, respectively.