Quantification of prefrontal cortical neuronal ensembles following conditioned fear learning in a Fos-LacZ transgenic rat with photoacoustic imaging in Vivo

• Published in: Photoacoustics (Munich) 2023-10, Vol.33, p.100551, Article 100551
• Main Authors: Matchynski, James I., Cilley, Timothy S., Sadik, Nareen, Makki, Kassem M., Wu, Min, Manwar, Rayyan, Woznicki, Alexander R., Kallakuri, Srinivasu, Arfken, Cynthia L., Hope, Bruce T., Avanaki, Kamran, Conti, Alana C., Perrine, Shane A.
• Format: Article
• Language: English
• Subjects: Fear-conditioning; Fos-LacZ transgenic rat; Functional imaging; Medial prefrontal cortex; Molecular imaging; Neuronal ensembles; Optoacoustic imaging; Photoacoustic imaging
• ISSN: 2213-5979; 2213-5979
• DOI: 10.1016/j.pacs.2023.100551

Understanding the neurobiology of complex behaviors requires measurement of activity in the discrete population of active neurons, neuronal ensembles, which control the behavior. Conventional neuroimaging techniques ineffectively measure neuronal ensemble activity in the brain in vivo because they assess the average regional neuronal activity instead of the specific activity of the neuronal ensemble that mediates the behavior. Our functional molecular photoacoustic tomography (FM-PAT) system allows direct imaging of Fos-dependent neuronal ensemble activation in Fos-LacZ transgenic rats in vivo. We tested four experimental conditions and found increased FM-PAT signal in prefrontal cortical areas in rats undergoing conditioned fear or novel context exposure. A parallel immunofluorescence ex vivo study of Fos expression found similar findings. These findings demonstrate the ability of FM-PAT to measure Fos-expressing neuronal ensembles directly in vivo and support a mechanistic role for the prefrontal cortex in higher-order processing of response to specific stimuli or environmental cues. •Direct imaging of Fos-dependent neuronal ensemble activation in transgenic rats in vivo.•Demonstrated similar Fos-expressing ensemble activation in both fear and sham conditioned animals.•Results replicated using parallel immunofluorescence study ex vivo.