Control over stress induces plasticity of individual prefrontal cortical neurons: A conductance-based neural simulation

Juan Varela,Andrew Varnell,Donald Cooper,Jungang Wang

doi:10.1038/npre.2011.6267.1

Abstract

AbstractBehavioral control over stressful stimuli induces resilience to future conditions when control is lacking. The medial prefrontal cortex(mPFC) is a critically important brain region required for plasticity of stress resilience. We found that control over stress induces plasticity of the intrinsic voltage-gated conductances of pyramidal neurons in the PFC. To gain insight into the underlying biophysical mechanisms of this plasticity we used the conductance- based neural simulation software tool, NEURON, to model the increase in membrane excitability associated with resilience to stress. A ball and stick multicompartment conductance-based model was used to realistically fit passive and active data traces from prototypical pyramidal neurons in neurons in rats with control over tail shock stress and those lacking control. The results indicate that the plasticity of membrane excitability associated with control over stress can be attributed to an increase in Na+ and Ca2+ T-type conductances and an increase in the leak conductance. Using simulated dendritic synaptic inputs we observed an increase in excitatory postsynaptic summation and amplification resulting in elevated action potential output. This realistic simulation suggests that control over stress enhances the output of the PFC and offers specific testable hypotheses to guide future electrophysiological mechanistic studies in animal models of resilience and vulnerability to stress.

Highlights

Based neural simulation software tool, NEURON, to model the increase in membrane excitability associated with UHVLOLHQFH WR VWUHVV $ EDOO DQG VWLFN PXOWLFRPSDUWPHQW FRQGXFWDQFHEDVHG PRGHO ZDV XVHG WR UHDOLVWLFDOO\ ¿W passive and active data traces from prototypical pyramidal neurons in neurons in rats with control over tail shock stress and those lacking control
To account for the di erence between the escapable shock (ES) and inescapable shock (IS) groups we modeled representative traces from each group (Fig. 1). e di erences are a re ection of changes in the biophysical properties of the neurons[4].We developed a simple ball and stick model and tted the data to elucidate the underlying conductances
We found that synaptic boosting occurs at more hyperpolarized resting potentials in ES compared to IS, from a

Summary

Brief Report neuroscience

Control over stress induces plasticity of individual prefrontal cortical neurons: A conductance-based neural simulation. Because of the dynamical voltage, time and morphological interactions involved in the integration of excitatory and inhibitory input to pyramidal neurons we utilized a simpli ed conductance-based modeling approach to determine which critical ion channels could be modi ed to produce the physiological ndings we observed. To accomplish this we utilized the neural simulation tool NEURON to examine the relationships between various conductances to t the measure physiological data, and determine the conductance changes between the di erent groups. To accomplish this we utilized the neural simulation tool NEURON to examine the relationships between various conductances to t the measure physiological data, and determine the conductance changes between the di erent groups. e utility of this approach is that we are able to re ne a model that allows hypothesis testing for future electrophysiological experiments to identify the précised cellular mechanisms of plasticity associated with control over stress

RESULTS

DISCUSSION

METHODS