Role of Glutamatergic Projections from Lateral Habenula to Ventral Tegmental Area in Inflammatory Pain-Related Spatial Working Memory Deficits

• Type: Article in International Scientific Journal
• Date: 2023-03-08

Authors

Mobina Alemi (Author) FMUP; Ana Pereira (Author) FMUP; Mariana Cerqueira-Nunes (Author) FMUP; Clara Monteiro (Author) FMUP; Vasco Galhardo (Author) FMUP; Helder Cardoso-Cruz (Author) FMUP

Journal

Title: Biomedicines

Vol. 11

Pages: 820-820

Publisher: MDPI

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Scientific classification

CORDIS: Health sciences > Neuroscience > Neurobiology ; Health sciences > Neuroscience > Neurophysiology

FOS: Medical and Health sciences > Basic medicine

Associated Projects

MEMORYSTIM - Modulação optogenética da sinalização GABAérgica e dopaminérgica do córtex préfrontal para a reversão de défices cognitivos relacionados com dor crónica

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

POCI-01-0145-FEDER-028498 - Codificação de sinais de recompensa em populações neuronais do circuito dopaminérgico: estudo optogenético dos correlatos neuronais de decisão e expectativa

Other information

Authenticus ID: P-00Y-5G6

DOI: 10.3390/biomedicines11030820

Abstract (EN): The lateral habenula (LHb) and the ventral tegmental area (VTA), which form interconnected circuits, have important roles in the crucial control of sensory and cognitive motifs. Signaling in the LHb-VTA pathway can be exacerbated during pain conditions by a hyperactivity of LHb glutamatergic neurons to inhibit local VTA DAergic cells. However, it is still unclear whether and how this circuit is endogenously engaged in pain-related cognitive dysfunctions. To answer this question, we modulated this pathway by expressing halorhodopsin in LHb neurons of adult male rats, and then selectively inhibited the axonal projections from these neurons to the VTA during a working memory (WM) task. Behavioral performance was assessed after the onset of an inflammatory pain model. We evaluated the impact of the inflammatory pain in the VTA synapses by performing immunohistochemical characterization of specific markers for GABAergic (GAD65/67) and dopaminergic neurons (dopamine transporter (DAT), dopamine D2 receptor (D2r) and tyrosine hydroxylase (TH)). Our results revealed that inhibition of LHb terminals in the VTA during the WM delay-period elicits a partial recovery of the performance of pain animals (in higher complexity challenges); this performance was not accompanied by a reduction of nociceptive responses. Finally, we found evidence that the pain-affected animals exhibit VTA structural changes, namely with an upregulation of GAD65/67, and a downregulation of DAT and D2r. These results demonstrate a role of LHb neurons and highlight their responsibility in the stability of the local VTA network, which regulates signaling in frontal areas necessary to support WM processes.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 20