Caitlynn De Preter (Mary Heinricher's Lab)

Caitlynn's LinkedIn

Department of Behavioral Neuroscience at Oregon Health & Science University, Portland, Oregon USA

I am a graduate student in the Heinricher Lab. We study how pain-modulating neurons in the brainstem respond to noxious stimuli and opioids. These probes allow us to answer new questions about how the brainstem neuron population works together to produce behavioral responses that we couldn't answer before with single electrodes.

The primary output of the brainstem pain-modulating system is the rostral ventromedial medulla (RVM). The RVM facilitates or suppresses nociceptive transmission at the level of the dorsal horn though two cell classes, termed “ON-” and “OFF-” cells. Over the last 30 years, the connectivity, physiology, and function of these neurons in pain-modulation has been extensively characterized using in-vivo electrophysiological recordings of single RVM neurons, identified by their response during noxious input: ON-cells exhibit a burst of activity, while OFF-cells exhibit a pause on ongoing activity just prior to nocifensive withdrawal. These evoked responses are attenuated after systemic morphine administration. ON- and OFF-cells fluctuate in activity in unstimulated conditions, with alternating silent and active periods. Between cell classes, ON- and OFF-cells display asynchronous ongoing and noxious evoked activity, while within each class, activity is in phase. Additionally, the ON-cell burst does not precede the pause of the OFF-cell, and pharmacological manipulation of the ON-cell burst does not influence OFF-cell activity. These parallel processes suggest that ON- and OFF-cell firing patterns reflect intrinsic excitability or coordinating input originating from outside the RVM. However, previous studies have relied on opportune recordings of paired single-units at a single local electrode site, or multiple electrodes in RVM at distant sites. Interactions within the RVM itself are almost entirely unknown. Using a 64-channel silicon probe, we simultaneously monitored the activity of numerous (15 to 40) single units in the RVM during noxious stimulation and systemic opioid administration in male and female Sprague-Dawley rats. We confirmed single-unit data that ON-cells are activated and OFF-cells were inhibited by noxious stimulation. In animals that became analgesic after morphine administration, the ON-cell burst and OFF-cell pause were attenuated as expected. OFF-cells were recruited after morphine administration. Rescue with naloxone also recruited ON-cells that were previously silent. Analysis of spike trains revealed that RVM neurons share common synaptic input and that some RVM neurons are monosynaptically interconnected. Additionally, while many cells could be classified as ON- or OFF-cells, these multichannel recordings revealed some cells that did not fit traditional classification parameters. The present data document within-RVM interactions using two approaches to classifying RVM neurons, and demonstrate the advantages of using multichannel recordings of pain-modulating neurons in brainstem