Reorganization of lateral habenula neuronal connectivity underlies pain-related impairment in spatial memory encoding

• Tipo: Artigo em Revista Científica Internacional
• Data: 2025-12-11

Autores

Helder Cardoso-Cruz (Autor) FMUP; Clara Monteiro (Autor) FMUP; Vasco Galhardo (Autor) FMUP

Revista

Título: Pain

Vol. 166

Páginas: 1532-1548

ISSN: 0304-3959

Editora: Wolters Kluwer Health

Indexação

ISI Web of Knowledge - 1 Citação

Scopus - 1 Citação

Pubmed / Medline

Classificação Científica

CORDIS: Ciências da Saúde > Neurociências

FOS: Ciências médicas e da saúde > Medicina básica

Projetos Associados

2022.05193.PTDC - Circuitos dopaminérgicos de codificação de hábitos e dependência em modelos animais de dor crónica

Outras Informações

ID Authenticus: P-017-KT2

DOI: 10.1097/j.pain.0000000000003493

Abstract (EN): Dysfunctional 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 CaMKII alpha (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 CaMKII alpha-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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 17