Memories of opiate withdrawal emotional states correlate with specific gamma oscillations in the nucleus accumbens
Dejean C*, Sitko* M, Girardeau P, Bennabi A, Caillé S, Cador M, Boraud T, Le Moine C.
Neuropsychopharmacology. 2017 Jan 4. doi: 10.1038/npp.2016.272. [Epub ahead of print]
Since G60 and G80 oscillations were acutely modulated by opiates and withdrawal in the NAC (Dejean et al, 2013), in this study ADDICTEAM investigated their role in the encoding and retrieval of opiate withdrawal memory. Using single unit and local field potential (LFP) recordings in behaving rats in a conditioned place aversion paradigm, we show that aversion and preference are correlated with a differential activity of NAC neurons, and that in both spike trains and LFP, this functional scheme emerges from specific interactions between G60 and G80 oscillations.
Our study highlights a candidate oscillatory mechanism supporting the coding of emotional memories in NAC neurons. This knowledge is crucial in the frame of the newly emerging therapies based on the manipulation of these memories for treating drug addiction or other emotional memory disorders
Abstract
Affective memories associated with the negative emotional state experienced during opiate withdrawal are central in maintaining drug-taking, seeking and relapse. Nucleus accumbens (NAC) is a key structure both for acute withdrawal and withdrawal memories reactivation, however NAC neuron coding properties underpinning the expression of these memories remain largely unknown. Here we aimed at deciphering the role of NAC neurons in the encoding and retrieval of opiate withdrawal memory.
Chronic single neuron and local field potentials recordings were performed in morphine-dependent rats and placebo-controls. Animals were subjected to an unbiased conditioned placed aversion protocol with one compartment (CS+) paired with naloxone-precipitated withdrawal, a second compartment with saline injection (CS-) and a third being neutral (no pairing). After conditioning, animals displayed a typical place aversion for CS+ and developed a preference for CS- characteristic of safety learning.
We found that distinct NAC neurons code for CS+ or CS-. Both populations also displayed highly specific oscillatory dynamics, CS+ and CS- neurons respectively following 80 Hz (G80) and 60 Hz (G60) local field potential gamma rhythms. Finally, we found that the balance between G60 and G80 rhythms strongly correlated both with the ongoing behavior of the animal as well as the strength of the conditioning.
We demonstrate here that the aversive and preferred environments are underpinned by distinct groups of NAC neurons as well as specific oscillatory dynamics. This suggest that G60/G80 interplay – established through the conditioning process- serves as a robust and versatile mechanism for a fine coding of the environment emotional weight.