Spontaneous recovery of fear reverses extinction-induced excitability of infralimbic neurons - PubMed (original) (raw)

Spontaneous recovery of fear reverses extinction-induced excitability of infralimbic neurons

Emmanuel Cruz et al. PLoS One. 2014.

Abstract

In rodents, the infralimbic (IL) region of the medial prefrontal cortex plays a key role in the recall of fear extinction. Previously we showed that fear conditioning decreases the intrinsic excitability of IL neurons, and that fear extinction reverses the depressed excitability. In the current study, we examined the time course of the extinction-induced changes in adolescent rats. Immediately after extinction, IL neurons continued to show depressed excitability. However 4 hours after extinction, IL neurons showed an increase in evoked spikes that correlated with a reduced fast afterhyperpolarizing potential. This suggests that acquisition of fear extinction induces an increase in spike firing 4 hours later, during the consolidation of extinction. We also examined IL excitability in a group of rats that showed spontaneous recovery of fear 17 days after extinction (SR group). Similar to neurons after fear conditioning, IL neurons from the SR group showed depressed intrinsic excitability compared to neurons 4 hours after extinction, suggesting that extinction-induced enhancement in intrinsic excitability decreases with time reverting back to a depressed state. These results suggest that plasticity in IL contributes to the spontaneous recovery of fear and preventing this depression of IL excitability could prolong fear extinction.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. The intrinsic excitability of IL pyramidal neurons increased within 4 hours after extinction and reversed with the spontaneous recovery of fear.

A. Percent of time that rats spent freezing to the tone in groups that were conditioned (Cond; n = 13 rats, black), and fear extinguished (Ext-0; n = 9 rats, red; Ext-4; n = 6 rats, blue; SR; n = 8 rats, green). The Ext-0 group was sacrificed immediately after extinction, and the Ext-4 group was sacrificed 4 hours after extinction. B. Average freezing of the SR group on day 3 and day 21 to two tones. SR rats were sacrificed immediately after testing on day 21. C. Sample traces showing responses of IL neurons from each group to a 200 pA depolarizing current step. D. Number of spikes evoked in IL neurons by increasing depolarizing steps in the Cond (n = 34), Ext-0 (n = 22), Ext-4 (n = 18), and SR (n = 18) groups. E. Average maximum number of spikes evoked in each group. F. Average first interspike interval (ISI). ***p<0.001, *p<0.05.

Figure 2

Figure 2. Spontaneous recovery reverses the decrease in fAHP induced by fear extinction.

A. Sample traces for each group showing fAHP measured within gray bar. Traces have been aligned to overlap at the spike threshold. B. Average of the fAHP for each group. C. Correlation between maximum number of spikes and fAHP for all neurons. D. Sample traces showing sAHP measured within gray bar. E. Average of the sAHP for each group. F. Lack of correlation between number of spikes and sAHP for all neurons. *p<0.05.

Figure 3

Figure 3. IL neurons of naïve age-matched rats are more excitable than IL neurons of the SR rats.

The number of spikes, ISI, fAHP, and sAHP of IL neurons (n = 15) of P50 naïve rats (n = 5) are shown normalized to the average values of the SR group. Dashed line indicates values of SR group.

Figure 4

Figure 4. Summary and model of the changes in IL intrinsic excitability at different behavioral time-points.

A. Average values of the measured intrinsic parameters. C = COND, E0 = EXT-0, E4 = EXT-4, E24 = 24 hours after extinction, SR = Spontaneous Recovery. Dash-line indicates values of naïve group. Naïve and E24 values used with permission from the Journal of Neuroscience (Santini et al., 2008). B. Schematic representation of IL and amygdala interactions at different behavioral time-points.

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References

    1. Amano T, Unal CT, Pare D (2010) Synaptic correlates of fear extinction in the amygdala. Nat Neurosci 13(4) p. 489–94. - PMC - PubMed
    1. Bouton M, Westbrook R, Corcoran K, Maren S (2006) Contextual and temporal modulation of extinction: behavioral and biological mechanisms. Biol Psychiatry 60 p. 352–360. - PubMed
    1. Burgos-Robles A, Vidal-Gonzalez I, Santini E, Quirk GJ (2007) Consolidation of Fear Extinction Requires NMDA Receptor-Dependent Bursting in the Ventromedial Prefrontal Cortex. Neuron 53(6) p. 871–80. - PubMed
    1. Cho JH, Deisseroth K, Bolshakov VY (2013) Synaptic encoding of fear extinction in mPFC-amygdala circuits. Neuron 80(6) p. 1491–507. - PMC - PubMed
    1. Dolen G, Bear MF (2008) Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome. J Physiol 586(6) p. 1503–8. - PMC - PubMed

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