µ-opioid receptor-mediated downregulation of midline thalamic pathways to basal and central amygdala

L Goedecke1, X Bengoetxea2, P Blaesse2

  • 1Institute of Physiology I, Westfaelische Wilhelms-Universitaet Muenster, Muenster, Germany. lena.goedecke@ukmuenster.de.

Scientific Reports
|November 30, 2019
PubMed

Insights

Brain µ-opioid receptors (MORs) in the dorsal midline thalamus dampen excitatory pathways to the amygdala. This finding reveals how MORs may reduce negative emotional states like pain and anxiety.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Behavioral Science

Background:

  • Brain µ-opioid receptors (MORs) are crucial for reward and managing negative emotions like pain, anxiety, and depression.
  • The dorsal midline thalamus (dMT) processes emotional signals and influences defensive behaviors via amygdala projections.
  • The precise role of MORs in modulating dMT-amygdala circuits is not fully understood.

Purpose of the Study:

  • To investigate the cellular and synaptic mechanisms of µ-opioid modulation within the dMT-amygdala circuitry.
  • To test the hypothesis that MORs negatively modulate excitatory networks in the dMT-amygdala pathway.

Main Methods:

  • Utilized retrograde tracers and channelrhodopsin-assisted circuit mapping.
  • Employed patch-clamp electrophysiology to record neuronal activity.
  • Examined MOR modulation of dMT projections to basal amygdala principal neurons (BA PN) and central amygdala (CeL) neurons.

Main Results:

  • Stimulation of MORs (somatic or synaptic) attenuated dMT neuron projections to both BA PN and CeL neurons.
  • MOR activation dampened the feedforward excitation of centromedial amygdala (CeM) neurons driven by dMT efferents.
  • Demonstrated that MORs act as negative modulators of excitatory activity in the dMT-amygdala pathway.

Conclusions:

  • µ-opioid receptor activation downregulates excitatory activity in dMT-amygdala networks.
  • This downregulation suggests a mechanism by which the µ-opioid system alleviates aversive states linked to stress, pain, and social rejection.

Related Concept Videos

Opioid Receptors: Overview01:22

Opioid Receptors: Overview

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
3.8K
Analgesia and Pain Management01:25

Analgesia and Pain Management

Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
1.4K
Regulation of Food Intake01:30

Regulation of Food Intake

Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
2.2K
Functional Brain Systems: Limbic System01:15

Functional Brain Systems: Limbic System

The limbic system, often called the "emotional brain," is a complex set of structures located deep within the brain. The intricate network of the limbic system supports a wide range of psychological functions, from emotional regulation to memory formation and sensory processing. This functional brain region encompasses specific parts of the diencephalon and the cerebrum, integrating the higher mental functions of the cerebral cortex with the primitive emotional responses of the deep brain...
6.1K
Opioid Analgesics: Synthetic and Semisynthetic Opioids01:15

Opioid Analgesics: Synthetic and Semisynthetic Opioids

Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
848
Role of Amygdala in Memory01:16

Role of Amygdala in Memory

The amygdala is a small, almond-shaped structure responsible for processing and storing memories, particularly those linked to emotions like fear and stress. It plays an essential role in the brain's response to emotionally significant events and often enhances memory formation by triggering stress hormone release. The amygdala is vital for encoding and retrieving memories associated with fear or stress, a process that is adaptive by helping organisms avoid dangerous situations.
One of the...
954