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Medial prefrontal cortex serotonin 1A and 2A receptor binding interacts to predict threat-related amygdala reactivity.

Fisher PM, Price JC, Meltzer CC, Moses-Kolko EL, Becker C, Berga SL, Hariri AR - Biol Mood Anxiety Disord (2011)

Bottom Line: The colocalization of 5-HT1A and 5-HT2A receptors on mPFC glutamatergic neurons suggests that their functional interactions may mediate 5-HT effects on this circuit through top-down regulation of amygdala reactivity.Specifically, mPFC 5-HT2A binding was significantly inversely correlated with amygdala reactivity only when mPFC 5-HT1A binding was relatively low.The effect of the interaction between mPFC 5-HT1A and 5-HT2A binding and amygdala reactivity is consistent with the colocalization of these receptors on glutamatergic neurons in the mPFC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. patrick.fisher@gmail.com.

ABSTRACT

Background: The amygdala and medial prefrontal cortex (mPFC) comprise a key corticolimbic circuit that helps shape individual differences in sensitivity to threat and the related risk for psychopathology. Although serotonin (5-HT) is known to be a key modulator of this circuit, the specific receptors mediating this modulation are unclear. The colocalization of 5-HT1A and 5-HT2A receptors on mPFC glutamatergic neurons suggests that their functional interactions may mediate 5-HT effects on this circuit through top-down regulation of amygdala reactivity. Using a multimodal neuroimaging strategy in 39 healthy volunteers, we determined whether threat-related amygdala reactivity, assessed with blood oxygen level-dependent functional magnetic resonance imaging, was significantly predicted by the interaction between mPFC 5-HT1A and 5-HT2A receptor levels, assessed by positron emission tomography.

Results: 5-HT1A binding in the mPFC significantly moderated an inverse correlation between mPFC 5-HT2A binding and threat-related amygdala reactivity. Specifically, mPFC 5-HT2A binding was significantly inversely correlated with amygdala reactivity only when mPFC 5-HT1A binding was relatively low.

Conclusions: Our findings provide evidence that 5-HT1A and 5-HT2A receptors interact to shape serotonergic modulation of a functional circuit between the amygdala and mPFC. The effect of the interaction between mPFC 5-HT1A and 5-HT2A binding and amygdala reactivity is consistent with the colocalization of these receptors on glutamatergic neurons in the mPFC.

No MeSH data available.


Amygdala reactivity to perceptual processing of fearful and angry facial expressions. Statistical parametric map representing bilateral amygdala clusters exhibiting a significant response to task (faces > shapes; right amygdala: (24, -6, -11), z = 6.28, k = 145 voxels (P < 0.05, corrected); left amygdala: (-18, -7, -15), z = 5.77, k = 146 voxels (P < 0.05, corrected). Color bar indicates t-scores.
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Figure 1: Amygdala reactivity to perceptual processing of fearful and angry facial expressions. Statistical parametric map representing bilateral amygdala clusters exhibiting a significant response to task (faces > shapes; right amygdala: (24, -6, -11), z = 6.28, k = 145 voxels (P < 0.05, corrected); left amygdala: (-18, -7, -15), z = 5.77, k = 146 voxels (P < 0.05, corrected). Color bar indicates t-scores.

Mentions: Consistent with previous reports, we observed robust threat-related reactivity in the bilateral amygdala across all participants [36,37] (Figure 1). The magnitude of right amygdala reactivity, but not left amygdala reactivity, was inversely correlated with age (right amygdala: r2 = 0.19, P = 0.005; left amygdala: r2 = 0.02, P = 0.35). Neither right nor left amygdala reactivity was correlated with gender (r2 values < 0.03, P values > 0.3).


Medial prefrontal cortex serotonin 1A and 2A receptor binding interacts to predict threat-related amygdala reactivity.

Fisher PM, Price JC, Meltzer CC, Moses-Kolko EL, Becker C, Berga SL, Hariri AR - Biol Mood Anxiety Disord (2011)

Amygdala reactivity to perceptual processing of fearful and angry facial expressions. Statistical parametric map representing bilateral amygdala clusters exhibiting a significant response to task (faces > shapes; right amygdala: (24, -6, -11), z = 6.28, k = 145 voxels (P < 0.05, corrected); left amygdala: (-18, -7, -15), z = 5.77, k = 146 voxels (P < 0.05, corrected). Color bar indicates t-scores.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3377121&req=5

Figure 1: Amygdala reactivity to perceptual processing of fearful and angry facial expressions. Statistical parametric map representing bilateral amygdala clusters exhibiting a significant response to task (faces > shapes; right amygdala: (24, -6, -11), z = 6.28, k = 145 voxels (P < 0.05, corrected); left amygdala: (-18, -7, -15), z = 5.77, k = 146 voxels (P < 0.05, corrected). Color bar indicates t-scores.
Mentions: Consistent with previous reports, we observed robust threat-related reactivity in the bilateral amygdala across all participants [36,37] (Figure 1). The magnitude of right amygdala reactivity, but not left amygdala reactivity, was inversely correlated with age (right amygdala: r2 = 0.19, P = 0.005; left amygdala: r2 = 0.02, P = 0.35). Neither right nor left amygdala reactivity was correlated with gender (r2 values < 0.03, P values > 0.3).

Bottom Line: The colocalization of 5-HT1A and 5-HT2A receptors on mPFC glutamatergic neurons suggests that their functional interactions may mediate 5-HT effects on this circuit through top-down regulation of amygdala reactivity.Specifically, mPFC 5-HT2A binding was significantly inversely correlated with amygdala reactivity only when mPFC 5-HT1A binding was relatively low.The effect of the interaction between mPFC 5-HT1A and 5-HT2A binding and amygdala reactivity is consistent with the colocalization of these receptors on glutamatergic neurons in the mPFC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. patrick.fisher@gmail.com.

ABSTRACT

Background: The amygdala and medial prefrontal cortex (mPFC) comprise a key corticolimbic circuit that helps shape individual differences in sensitivity to threat and the related risk for psychopathology. Although serotonin (5-HT) is known to be a key modulator of this circuit, the specific receptors mediating this modulation are unclear. The colocalization of 5-HT1A and 5-HT2A receptors on mPFC glutamatergic neurons suggests that their functional interactions may mediate 5-HT effects on this circuit through top-down regulation of amygdala reactivity. Using a multimodal neuroimaging strategy in 39 healthy volunteers, we determined whether threat-related amygdala reactivity, assessed with blood oxygen level-dependent functional magnetic resonance imaging, was significantly predicted by the interaction between mPFC 5-HT1A and 5-HT2A receptor levels, assessed by positron emission tomography.

Results: 5-HT1A binding in the mPFC significantly moderated an inverse correlation between mPFC 5-HT2A binding and threat-related amygdala reactivity. Specifically, mPFC 5-HT2A binding was significantly inversely correlated with amygdala reactivity only when mPFC 5-HT1A binding was relatively low.

Conclusions: Our findings provide evidence that 5-HT1A and 5-HT2A receptors interact to shape serotonergic modulation of a functional circuit between the amygdala and mPFC. The effect of the interaction between mPFC 5-HT1A and 5-HT2A binding and amygdala reactivity is consistent with the colocalization of these receptors on glutamatergic neurons in the mPFC.

No MeSH data available.