Reciprocally inhibitory circuits operating with distinct mechanisms are differently robust to perturbation and modulation

Abstract

Reciprocal inhibition is a building block in many sensory and motor circuits. We studied the features that underly robustness in reciprocally inhibitory two neuron circuits. We used the dynamic clamp to create reciprocally inhibitory circuits from pharmacologically isolated neurons of the crab stomatogastric ganglion by injecting artificial graded synaptic (ISyn) and hyperpolarization-activated inward (IH) currents. There is a continuum of mechanisms in circuits that generate antiphase oscillations, with 'release' and 'escape' mechanisms at the extremes, and mixed mode oscillations in between these extremes. In release, the active neuron primarily controls the off/on transitions. In escape, the inhibited neuron controls the transitions. We characterized the robustness of escape and release circuits to alterations in circuit parameters, temperature, and neuromodulation. We found that escape circuits rely on tight correlations between synaptic and H conductances to generate bursting but are resilient to temperature increase. Release circuits are robust to variations in synaptic and H conductances but fragile to temperature increase. The modulatory current (IMI) restores oscillations in release circuits but has little effect in escape circuits. Perturbations can alter the balance of escape and release mechanisms and can create mixed mode oscillations. We conclude that the same perturbation can have dramatically different effects depending on the circuits' mechanism of operation that may not be observable from basal circuit activity.

Degeneracy in epilepsy: multiple routes to hyperexcitable brain circuits and their repair

“…However, following identical pathological perturbations, such as a reduction of inhibition or cell type diversity, these models displayed heterogeneous circuit responses. This is in agreement with previous work showing that perturbations in degenerate, superficially similar circuits can reveal hidden variability in synaptic and intrinsic properties leading to heterogeneous responses 8 , 41 , 250 , 251 . Such modelling insights are highly relevant also for epilepsy.…”

“… 7 . In contrast to redundant components, degenerate components may generate dissimilar outputs in different contexts 2 , 8 . Therefore, although degeneracy is sometimes called also ‘partial redundancy’ 9 , we follow the terminology of Edelman and Gally 1 and distinguish degeneracy from redundancy.…”

A half-centre oscillator encodes sleep pressure

“…In contrast to SWA in mammals, which can be recorded across the entire cortical surface during NREM sleep 7 , dFBN slow waves are products of an anatomically circumscribed central pattern generator that may be numerically as simple as the two-neuron swim circuit of Clione 10 . Despite their apparent simplicity, central pattern generators are notorious for the sensitivity of their dynamics to modulatory changes in biophysical parameters 34 -36 . dFBNs experience many such changes as sleep pressure builds: they steepen their current–spike frequency functions 2,3 , modulate voltage-gated and leak potassium conductances in opposite directions 6 , and receive heightened (indirect) excitatory drive from R5 neurons 37 .…”

Feeding-state dependent neuropeptidergic modulation of reciprocally interconnected inhibitory neurons biases sensorimotor decisions inDrosophila

“…13 Calcium imaging combined with neuronal manipulations revealed that, in the circuit for selecting between the Hunch and the Head Cast, inhibitory neurons (and not the projection neurons) are the target of modulation by the changes in the feeding conditions. Inhibitory neurons were shown to be the target of contextual modulation in other systems [57][58][59] . Previous work has identified reciprocal inhibition of inhibition as a motif underlying the competition between a startle-type action and an exploratory action 35 .…”