Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/121657
Author(s): Helder Cardoso-Cruz
Pedro Paiva
Clara Monteiro
Vasco Galhardo
Title: Bidirectional optogenetic modulation of prefrontal-hippocampal connectivity in pain-related working memory deficits
Issue Date: 2019-07-29
Abstract: 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 (CaMKIIα) 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 CaMKIIα-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 CaMKIIα-expressing neurons could be modulated by painful conditions and their activity may be critical for prefrontal-hippocampal connectivity during WM processing.
Subject: Ciências da Saúde, Neurociências, Medicina básica
Health sciences, Neuroscience, Basic medicine
Scientific areas: Ciências médicas e da saúde::Medicina básica
Medical and Health sciences::Basic medicine
URI: https://hdl.handle.net/10216/121657
Related Information: info:eu-repo/grantAgreement/FCT - Fundação para a Ciência e Tecnologia/COMPETE - Programa Operacional Fatores de Competitividade/POCI-01-0145-FEDER-028181/Modulação optogenética da sinalização GABAérgica e dopaminérgica do córtex préfrontal para a reversão de défices cognitivos relacionados com dor crónica/MEMORYSTIM
info:eu-repo/grantAgreement/FCT - Fundação para a Ciência e Tecnologia/COMPETE - Programa Operacional Fatores de Competitividade/POCI-01-0145-FEDER-028498/OPTORISK/POCI-01-0145-FEDER-028498
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:FMUP - Artigo em Revista Científica Internacional

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