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Serotonin Gating of Cortical and Thalamic Glutamate Inputs Onto Principal Neurons of the Basolateral Amygdala

Overview
Specialties Neurology
Pharmacology
Date 2017 Sep 14
PMID 28899729
Citations 14
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Abstract

The basolateral amygdala (BLA) is a key site for crossmodal association of sensory stimuli and an important relay in the neural circuitry of emotion. Indeed, the BLA receives substantial glutamatergic inputs from multiple brain regions including the prefrontal cortex and thalamic nuclei. Modulation of glutamatergic transmission in the BLA regulates stress- and anxiety-related behaviors. Serotonin (5-HT) also plays an important role in regulating stress-related behavior through activation of both pre- and postsynaptic 5-HT receptors. Multiple 5-HT receptors are expressed in the BLA, where 5-HT has been reported to modulate glutamatergic transmission. However, the 5-HT receptor subtype mediating this effect is not yet clear. The aim of this study was to use patch-clamp recordings from BLA neurons in an ex vivo slice preparation to examine 1) the effect of 5-HT on extrinsic sensory inputs, and 2) to determine if any pathway specificity exists in 5-HT regulation of glutamatergic transmission. Two independent input pathways into the BLA were stimulated: the external capsule to mimic cortical input, and the internal capsule to mimic thalamic input. Bath application of 5-HT reversibly reduced the amplitude of evoked excitatory postsynaptic currents (eEPSCs) induced by stimulation of both pathways. The decrease was associated with an increase in the paired-pulse ratio and coefficient of variation of eEPSC amplitude, suggesting 5-HT acts presynaptically. Moreover, the effect of 5-HT in both pathways was mimicked by the selective 5-HT receptor agonist CP93129, but not by the 5-HT receptor agonist 8-OH DPAT. Similarly the effect of exogenous 5-HT was blocked by the 5-HT receptor antagonist GR55562, but not affected by the 5-HT receptor antagonist WAY 100635 or the 5-HT receptor antagonists pirenperone and MDL 100907. Together these data suggest 5-HT gates cortical and thalamic glutamatergic inputs into the BLA by activating presynaptic 5-HT receptors.

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References
1.
Fink K, Gothert M . 5-HT receptor regulation of neurotransmitter release. Pharmacol Rev. 2007; 59(4):360-417. DOI: 10.1124/pr.107.07103. View

2.
Murrough J, Henry S, Hu J, Gallezot J, Planeta-Wilson B, Neumaier J . Reduced ventral striatal/ventral pallidal serotonin1B receptor binding potential in major depressive disorder. Psychopharmacology (Berl). 2010; 213(2-3):547-53. PMC: 3139174. DOI: 10.1007/s00213-010-1881-0. View

3.
Ismaiel A, Titeler M, Miller K, Smith T, Glennon R . 5-HT1 and 5-HT2 binding profiles of the serotonergic agents alpha-methylserotonin and 2-methylserotonin. J Med Chem. 1990; 33(2):755-8. DOI: 10.1021/jm00164a046. View

4.
Abrams J, Johnson P, Hollis J, Lowry C . Anatomic and functional topography of the dorsal raphe nucleus. Ann N Y Acad Sci. 2004; 1018:46-57. DOI: 10.1196/annals.1296.005. View

5.
Ostrowski T, Ostrowski D, Hasser E, Kline D . Depressed GABA and glutamate synaptic signaling by 5-HT1A receptors in the nucleus tractus solitarii and their role in cardiorespiratory function. J Neurophysiol. 2014; 111(12):2493-504. PMC: 4044435. DOI: 10.1152/jn.00764.2013. View