Bidirectional optogenetic modulation of prefrontal-hippocampal connectivity in pain-related working memory deficits

• Type: Article in International Scientific Journal
• Date: 2019-07-29

Authors

Helder Cardoso-Cruz (Author) Other; Pedro Paiva (Author) Other; Clara Monteiro (Author) FMUP; Vasco Galhardo (Author) FMUP

Journal

Title: Scientific Reports

Vol. 9 No. 3413

ISSN: 2045-2322

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 12 Citations

Scopus - 11 Citations

Pubmed / Medline

Scientific classification

CORDIS: Health sciences ; Health sciences > Neuroscience

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

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-00Q-W8V

DOI: 10.1038/s41598-019-47555-0

Abstract (EN): Dysfunction of the prefrontal-hippocampal circuit has been identified as a leading cause to pain-related working-memory (WM) deficits. However, the underlying mechanisms remain poorly determined. To address this issue, we implanted multichannel arrays of electrodes in the prelimbic cortex (PL-mPFC), and in the dorsal hippocampal CA1 field (dCA1) to record the neural activity during the performance of a delayed non-match to sample (DNMS) task. The prefrontal-hippocampal connectivity was selectively modulated by bidirectional optogenetic inhibition or stimulation of local PL-mPFC glutamatergic calcium/calmodulin-dependent protein kinase-II alpha (CaMKIIa) expressing neurons during the DNMS task delay-period. The within-subject behavioral performance was assessed using a persistent neuropathic pain model - spared nerve injury (SNI). Our results showed that the induction of the neuropathic pain condition affects the interplay between PL-mPFC and dCA1 regions in a frequency-dependent manner, and that occurs particularly across theta oscillations while rats performed the task. In SNI-treated rats, this disruption was reversed by the selective optogenetic inhibition of PL-mPFC CaMKIIa-expressing neurons during the last portion of the delay-period, but without any significant effect on pain responses. Finally, we found that prefrontal-hippocampal theta connectivity is strictly associated with higher performance levels. Together, our findings suggest that PL-mPFC CaMKII alpha-expressing neurons could be modulated by painful conditions and their activity may be critical for prefrontal-hippocampal connectivity during WM processing.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17