Releasing the Brake Drives Fear Behavior

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Science Translational Medicine  15 Jan 2014:
Vol. 6, Issue 219, pp. 219ec12
DOI: 10.1126/scitranslmed.3008282

Although modern neuroscience has identified many brain circuits and cell types that contribute to behaviors that model aspects of psychiatric disorders, understanding how specific patterns of activity within these circuits drive behavior has been more challenging. In a recent study, Courtin et al. show how a specific class of inhibitory interneurons, which express the calcium binding protein parvalbumin (PV), modulate activity in the dorsomedial prefrontal cortex and thereby control the expression of fear behavior in mice.

Courtin et al. recorded the firing of individual neurons, as well as local field potentials that reflect activity from many neurons within the dorsomedial prefrontal cortex during fear conditioning in mice. They found that presentation of a conditioned stimulus, such as a tone that has been associated with foot shock, led to three effects: a decrease in the firing of many PV interneurons, an increase in the firing of many excitatory pyramidal neurons, and a resetting of the phase of theta oscillations in local field potentials. They go on to show that the decrease in PV interneuron firing drives the other two phenomena. Specifically, using the light-activated proton pump Archaeorhodopsin to inhibit PV interneurons, the authors reproduced the increase in pyramidal neuron firing and the resetting of the theta phase that typically follows the conditioned stimulus. In contrast, activating PV interneurons by using the light-activated cation channel rhodopsin blocked the ability of the conditioned stimulus to elicit these two effects. Furthermore, inhibiting or activating PV interneurons induced or suppressed freezing, respectively, demonstrating that these PV interneuron–driven changes in neural activity control fear expression.

Many of the pyramidal neurons that are inhibited by PV interneurons project to the basolateral amygdala, which mediates the expression and storage of fear memories. Thus, by disinhibiting pyramidal neurons that project to the basolateral amygdala and by modulating their synchrony with respect to theta oscillations, the conditioned stimulus-elicited suppression of PV interneuron firing may enhance output from the dorsomedial prefrontal cortex to the basolateral amygdala, leading to freezing. These results elucidate how specific patterns of activity within the dorsomedial prefrontal cortex–basolateral amygdala circuit drive the expression of fear behaviors. The next steps include identifying specific mechanisms through which the conditioned stimulus suppresses PV interneuron firing and understanding how the patterns of activity described above may be altered under pathological conditions, such as post-traumatic stress disorder, that lead to the overexpression of fear behaviors.

J. Courtin et al., Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression, Nature 505, 92–96 (2014). [PubMed]

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