Impaired pain in mice lacking first-order posterior medial thalamic neurons

Author:

Sgourdou Paraskevi1,Schaffler Melanie2,Choi Kyuhyun2,McCall Nora M.23,Burdge Justin45,Williams Joelle1,Corder Gregory23,Fuccillo Marc V.2,Abdus-Saboor Ishmail45,Epstein Douglas J.1

Affiliation:

1. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

2. Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

3. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States

4. Department of Biology, University of Pennsylvania, Philadelphia, PA, United States

5. Zuckerman Mind Brain Behavior Institute, Department of Biological Sciences, Columbia University, Jerome L. Greene Center, New York, NY, United States

Abstract

Abstract The thalamus plays an important role in sensory and motor information processing by mediating communication between the periphery and the cerebral cortex. Alterations in thalamic development have profound consequences on sensory and motor function. In this study, we investigated a mouse model in which thalamic nuclei formation is disrupted because of the absence of Sonic hedgehog (Shh) expression from 2 key signaling centers that are required for embryonic forebrain development. The resulting defects observed in distinct thalamic sensory nuclei in Shh mutant embryos persisted into adulthood prompting us to examine their effect on behavioral responses to somatosensory stimulation. Our findings reveal a role for first-order posterior medial thalamic neurons and their projections to layer 4 of the secondary somatosensory cortex in the transmission of nociceptive information. Together, these results establish a connection between a neurodevelopmental lesion in the thalamus and a modality-specific disruption in pain perception.

Funder

NIH

Publisher

Ovid Technologies (Wolters Kluwer Health)

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