• Helder Cardoso-Cruz, Clara Monteiro, and Vasco Galhardo.
• Instituto de Investigação e Inovação em Saúde (i3S), Pain Neurobiology Research Group, Universidade do Porto, Porto, Portugal.
• Pain. 2024 Dec 11.

AbstractDysfunctional hyperactivity of the lateral habenula nucleus (LHb) has emerged as a critical marker for pain-related mood impairments. Acting as a central hub, the LHb filters and disseminates pertinent information to other brain structures during learning. However, it is not well understood how intra-LHb activity is altered during cognitive demand under neuropathic pain conditions. To address this gap, we implanted an optrode structure to record neuronal activity in adult male CD (rat strain without definition) rats during the execution of a delayed nonmatch-to-sample (DNMS) spatial working memory (WM) task. We selectively modulated intra-LHb network activity by optogenetically inhibiting local LHb CaMKIIα (calcium calmodulin-dependent protein kinase II alpha)-expressing neurons during the delay phase of the DNMS task. Behavioral assessments were conducted using a persistent rodent model of neuropathic pain-spared nerve injury. Our results showed that the induction of neuropathic pain disrupted WM encoding accuracy and intra-LHb functional neuronal connectivity. This disruption was reversed by optogenetic inhibition of LHb CaMKIIα-expressing neurons, which also produced antinociceptive effects. Together, our findings provide insight into how intra-LHb networks reorganize information to support different task contexts, suggesting that the abnormal pain-related intra-LHb dynamic segregation of information may contribute to poor cognitive accuracy in male rodents during pain experiences.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.

12 keywords...

hide…