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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.


Related in: MedlinePlus

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.


Related in: MedlinePlus