Viral‐genetic Mapping of Neural Circuit Organization of Nociceptive Neurons in the Thalamus

Abstract

There is a critical need to determine the location, connections and neurochemical identities of neurons participating in the transmission and modulation of pain in the CNS so that these circuits can be precisely targeted for pain intervention. Without such knowledge the development of effective, low side‐effect pain treatments will be difficult. In this talk I will report our progress using recent technological advancements to determine detailed neural activation patterns and synaptic circuit organization of neurons related to pain sensation and modulation in the thalamus. We have identified and visualized thalamic nociceptive neurons activated by chronic pain, using a strategy of genetic capture of active neurons on the basis of activity dependent c‐fos gene expression. Specifically, pain‐activated neurons are captured using Fos‐CreER mice with tamoxifen‐dependent recombinase CreERT2 under the promoter of the immediate early gene c‐fos. These mice are crossed with Cre reporter Ai9 mice to express tdTomato fluorescent proteins. A noxious stimulus is evoked by injection of complete Freund's adjuvant (CFA) into the hind paw; only neurons that are functionally active within a limited time window of 4‐OHT administration are genetically labeled. Then we build on this technical development to combine the Fos‐CreER based strategy with new viral tracing of circuit connections to nociceptive neurons in the ventral posterolateral (VPL) nucleus. Genetically modified rabies is used to trace global direct synaptic connections to pain activated neurons in VPL. These studies allow us to map molecular and neurochemical identities (e.g., excitatory versus inhibitory) of whole brain‐wide presynaptic neurons that are directly connected to thalamic nociceptive neurons. We foresee that this new research can address the critical barrier in the field and will advance our understanding of thalamic nociceptive neuron circuits and pain modulating processes.Support or Funding InformationStart‐up funds from Texas A&M UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.