Oxytocin increases inhibitory synaptic transmission and blocks development of long-term potentiation in the lateral amygdala.

R F Westbrook,N M Holmes,A J Delaney,J W Crane,J Fam

doi:10.1152/jn.00571.2019

R F Westbrook, N M Holmes + Show 3 more

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https://doi.org/10.1152/jn.00571.2019

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Abstract

Oxytocin (OT) is a neuroactive peptide that influences the processing of fearful stimuli in the amygdala. In the central nucleus of the amygdala, the activation of OT receptors alters neural activity and ultimately suppresses the behavioral response to a fear conditioned stimulus. Receptors for OT are also found in the lateral amygdala (LA), and infusion of OT into the basolateral amygdala complex affects the formation and consolidation of fear memories. Yet, how OT receptor activation alters neurons and neural networks in the LA is unknown. In this study we used whole cell electrophysiological recordings to determine how OT-receptor activation changes synaptic transmission and synaptic plasticity in the LA of Sprague-Dawley rats. Our results demonstrate that OT-receptor activation results in a 200% increase in spontaneous inhibitory transmission in the LA that leads to the activation of presynaptic GABAB receptors. The activation of these receptors inhibits excitatory transmission in the LA, blocking long-term potentiation of cortical inputs onto LA neurons. Hence, this study provides the first demonstration that OT influences synaptic transmission and plasticity in the LA, revealing a mechanism that could explain how OT regulates the formation and consolidation of conditioned fear memories in the amygdala.NEW & NOTEWORTHY This study investigates modulation of synaptic transmission by oxytocin (OT) in the lateral amygdala (LA). We demonstrate that OT induces transient increases in spontaneous GABAergic transmission by activating interneurons in the basolateral amygdala. The resultant increase in GABA release in the LA activates presynaptic GABAB receptors on both inhibitory and excitatory inputs onto LA neurons, reducing release probability at these synapses. We subsequently demonstrate that OT modulates synaptic plasticity at cortical inputs to the LA.

Highlights

Oxytocin (OT) is a nine-amino acid-long peptide that is synthesized and released by neurons in the paraventricular and supraoptic nuclei of the hypothalamus
We have previously shown that infusion of OT into the basolateral amygdala (BLA) impairs the formation of conditioned fear memories (Campbell-Smith et al 2015) and enhances the brain’s ability to discriminate sensory cues that predict danger from those that do not (Fam et al 2018)
We demonstrate that OT increases inhibitory transmission in the lateral amygdala (LA) and that this increase results in activation of presynaptic GABAB receptors that suppress excitatory neurotransmission in the LA

Summary

Introduction

Oxytocin (OT) is a nine-amino acid-long peptide that is synthesized and released by neurons in the paraventricular and supraoptic nuclei of the hypothalamus. Hypothalamic OT neurons project into many extrahypothalamic brain regions that contain oxytocin receptors (OTRs) (Elands et al 1988; Freund-Mercier et al 1987; Huber et al 2005; Klein et al 1995; Tribollet et al 1988) One of these regions, the amygdala, plays a critical role in processing emotionally charged stimuli and generating responses to these stimuli (Adolphs 2013). We have recently found that infusions of OT into the BLA influence how rats process a compound of cues (tone-light) that predict a footshock, suggesting that activation of OTRs in the BLA influences neural networks that encode and store conditioned fear memories

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