Thalamic Retrieval of Opioid Memories

Abstract

Opioids are commonly used as analgesics for severe pain, but their addictive potential has sparked a misuse epidemic. In this issue of Neuron, Keyes et al. (2020) examine the contributions of distinct paraventricular thalamus (PVT) outputs to contextual opioid memories. They identify a PVT→NAc→LH circuit essential for recall of opioid experiences.

Keywords: brain-wide c-Fos; central amygdala; chemogenetics; drug-related memory; lateral hypothalamus; morphine; nucleus accumbens; opioids; optogenetics; paraventricular thalamus.

Figure 1.. Neural Circuit Model of PVT Control over Opioid Memory Formation and Retrieval

The PVT receives input from several structures, including the prefrontal cortex (PFC), insular cortex (IC), hypothalamus (HYP), and ventral hippocampus (vHC). Information is then conveyed by excitatory outputs to downstream targets, including the CeA and the NAc. Keyes et al. (2020) show that the PVT→CeA projection contributes to opioid memory formation, whereas the PVT→NAc projection is required for opioid memory retrieval. D2-MSN-mediated inhibition of LH-projecting D1-MSNs is increased by opioid exposure, decreasing D1-MSN activity and disinhibiting the LH. The PVT→NAc→LH pathway causes brain-wide activation of downstream targets during morphine CPP relapse. Orange: neurons activated during opioid memory formation or retrieval. Blue: neurons inhibited during opioid memory retrieval.