Altered prefrontal-striatal theta-band oscillatory dynamics underlie working memory deficits in neuropathic pain rats

• Type: Article in International Scientific Journal
• Date: 2022-05-23

Authors

Helder Cardoso-Cruz (Author) FMUP; Inês Laranjeira (Author) Other; Clara Monteiro (Author) FMUP; Vasco Galhardo (Author) FMUP

Journal

Title: European Journal of Pain

Vol. 26

Pages: 1546-1568

ISSN: 1090-3801

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 2 Citations

Pubmed / Medline

Scientific classification

CORDIS: Health sciences ; 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

Other information

Authenticus ID: P-00W-MTB

DOI: 10.1002/ejp.1982

Abstract (EN): Background Prelimbic medial prefrontal cortex (PL-mPFC) and nucleus accumbens core region (NAcc) play an important role in supporting several executive cognitive mechanisms, such as spatial working memory (WM). Recently, this circuit has been also associated with both sensory and affective components of pain. However, it is still unclear whether this circuit is endogenously engaged in neuropathic pain-related cognitive dysfunctions. Methods To answer this question, we induced the expression of halorhodopsin in local PL-mPFC neurons projecting to NAcc, and then selectively inhibited the terminals of these neurons in the NAcc while recording neural activity during the performance of a delayed non-match to sample (DNMS) spatial WM task. Within-subject behavioural performance and PL-mPFC to NAcc circuit neural activity was assessed after the onset of a persistent rodent neuropathic pain model-spared nerve injury (SNI). Results Our results revealed that the induction of the neuropathy reduced WM performance, and altered the interplay between PL-mPFC and NAcc neurons namely in increasing the functional connectivity from NAcc to PL-mPFC, particularly in the theta-band spontaneous oscillations; in addition, these behavioural and functional perturbations were partially reversed by selective optogenetic inhibition of PL-mPFC neuron terminals into the NAcc during the DNMS task delay-period, without significant antinociceptive effects. Conclusions Altogether, these results strongly suggest that the PL-mPFC excitatory output into the NAcc plays an important role in the deregulation of WM under pain conditions. Significance Selective optogenetic inhibition of prefrontal-striatal microcircuit reverses pain-related working memory deficits but has no significant impact on pain responses. Neuropathic pain underlies an increase of functional connectivity between the nucleus accumbens core area and the prelimbic medial prefrontal cortex mediated by theta-band activity.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 23