Rate and Temporal Coding Mechanisms in the Anterior Cingulate Cortex for Pain Anticipation

Louise Urien,Zhe Chen,Jahrane Dale,Jing Wang,Zhengdong Xiao,Elizabeth P Bauer

doi:10.1038/s41598-018-26518-x

Abstract

Pain is a complex sensory and affective experience. Through its anticipation, animals can learn to avoid pain. Much is known about passive avoidance during a painful event; however, less is known about active pain avoidance. The anterior cingulate cortex (ACC) is a critical hub for affective pain processing. However, there is currently no mechanism that links ACC activities at the cellular level with behavioral anticipation or avoidance. Here we asked whether distinct populations of neurons in the ACC can encode information for pain anticipation. We used tetrodes to record from ACC neurons during a conditioning assay to train rats to avoid pain. We found that in rats that successfully avoid acute pain episodes, neurons that responded to pain shifted their firing rates to an earlier time, whereas neurons that responded to the anticipation of pain increased their firing rates prior to noxious stimulation. Furthermore, we found a selected group of neurons that shifted their firing from a pain-tuned response to an anticipatory response. Unsupervised learning analysis of ensemble spike activity indicates that temporal spiking patterns of ACC neurons can indeed predict the onset of pain avoidance. These results suggest rate and temporal coding schemes in the ACC for pain avoidance.

Highlights

We found that neurons that tended to fire during the anticipation period increased their firing rate, possibly contributing to an escape behavior, whereas neurons that typically responded to pain fired earlier in response to the noxious stimulus
The latency of withdrawal was quantified in regard to the time of laser ON: a withdrawal occurring between laser ON and OFF was counted as a positive value and labelled a “withdrawal” trial
We asked if a selected group of neurons within the anterior cingulate cortex (ACC) could encode pain anticipation, contributing to avoidance behaviors

Summary

Introduction

As avoidance is a progressive learned behavior, time and rate firing of specific ACC neurons may contribute to a fine-tuning of pain anticipation. We performed in vivo electrophysiological recordings of ACC neurons in these awake, free-behaving rats, during the conditioning assay. These recordings allowed us to identify a number of individual ACC neurons selectively responding to the anticipation of pain, or the pain stimulus itself. We found specific ACC neurons that shifted their firing from a pain-tuned response to an earlier “anticipatory” response. Together, these three groups of neurons can provide important information for pain anticipation and avoidance. Unsupervised machine-learning analysis of single-trial population spike data demonstrated accurate detection of the timing of pain anticipation, further confirming the rate and temporal coding mechanisms in the ACC for pain anticipation

Methods

Results

Conclusion