Hidden synaptic differences in a neural circuit underlie differential behavioral susceptibility to a neural injury.

Akira Sakurai,Paul S Katz,Arianna N Tamvacakis

doi:10.7554/elife.02598

Abstract

Individuals vary in their responses to stroke and trauma, hampering predictions of outcomes. One reason might be that neural circuits contain hidden variability that becomes relevant only when those individuals are challenged by injury. We found that in the mollusc, Tritonia diomedea, subtle differences between animals within the neural circuit underlying swimming behavior had no behavioral relevance under normal conditions but caused differential vulnerability of the behavior to a particular brain lesion. The extent of motor impairment correlated with the site of spike initiation in a specific neuron in the neural circuit, which was determined by the strength of an inhibitory synapse onto this neuron. Artificially increasing or decreasing this inhibitory synaptic conductance with dynamic clamp correspondingly altered the extent of motor impairment by the lesion without affecting normal operation. The results suggest that neural circuit differences could serve as hidden phenotypes for predicting the behavioral outcome of neural damage.

Highlights

Experimental and theoretical studies have shown that individual animals can exhibit similar behaviors while differing substantially in the properties of the neurons and synapses underlying those behaviors (Prinz et al, 2004; Goaillard et al, 2009; Calabrese et al, 2011; Norris et al, 2011; Roffman et al, 2012)
We previously showed that when one of the pedal commissures, Pedal Nerve 6 (PdN6), was severed (Figure 1C), the swimming behavior of the animal was impaired in that the number of body flexions per swim episode decreased compared to sham-operated controls (Sakurai and Katz, 2009b)
We could not detect a correlation between the initial depolarization phase and the number of VSI bursts (p = 0.07, N = 26; not shown). These results indicate that the variability in the susceptibility of the motor pattern to PdN6 disconnection originates at least in part from the difference in the extent to which cerebral 2 (C2) inhibits VSI; animals in which C2 evoked larger hyperpolarizations in VSI were more vulnerable to having their motor pattern disrupted

Summary

Introduction

Experimental and theoretical studies have shown that individual animals can exhibit similar behaviors while differing substantially in the properties of the neurons and synapses underlying those behaviors (Prinz et al, 2004; Goaillard et al, 2009; Calabrese et al, 2011; Norris et al, 2011; Roffman et al, 2012) The consequences of such hidden variability in neural circuits have not been addressed. It has been noted that individual people differ from one another to such an extent that it can impair the ability to predict outcomes in cases of traumatic brain injury (Hukkelhoven et al, 2005; Lingsma et al, 2010; Forsyth and Kirkham, 2012) or stroke (Cramer, 2008a) Such variability can be hidden under normal conditions but cause differential survival of individuals in the face of critical challenges. We report that differences in synaptic properties, which were of no consequence under ordinary conditions, caused different outcomes when the circuit was challenged with an injury

Methods

Results

Conclusion