title: Prefrontal cortex and mediodorsal thalamus reduced connectivity is associated with spatial working memory impairment in rats with inflammatory pain.
abstract: The medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) form interconnected neural circuits that are important for spatial cognition and memory, but it is not known whether the functional connectivity between these areas is affected by the onset of an animal model of inflammatory pain. To address this issue, we implanted 2 multichannel arrays of electrodes in the mPFC and MD of adult rats and recorded local field potential activity during a food-reinforced spatial working memory task. Recordings were performed for 3weeks, before and after the establishment of the pain model. Our results show that inflammatory pain caused an impairment of spatial working memory performance that is associated with changes in the activity of the mPFC-MD circuit; an analysis of partial directed coherence between the areas revealed a global decrease in the connectivity of the circuit. This decrease was observed over a wide frequency range in both the frontothalamic and thalamofrontal directions of the circuit, but was more evident from MD to mPFC. In addition, spectral analysis revealed significant oscillations of power across frequency bands, namely with a strong theta component that oscillated after the onset of the painful condition. Finally, our data revealed that chronic pain induces an increase in theta/gamma phase coherence and a higher level of mPFC-MD coherence, which is partially conserved across frequency bands. The present results demonstrate that functional disturbances in mPFC-MD connectivity are a relevant cause of deficits in pain-related working memory.
authors.affiliation: IBMC - Instituto de Biologia Molecular e Celular, Grupo de Morfofisiologia do Sistema Somatosensitivo, Universidade do Porto, 4150-180 Porto, Portugal Departamento de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal Programa Doutoral em Neurociências, Faculdade de Medicina, Universidade do Porto, 4200-319 Porto, Portugal Laboratório de Neuropsicofisiologia, Faculdade de Psicologia e Ciências da Educação, Universidade do Porto, 4200-392 Porto, Portugal.
authors.forename: Helder
authors.initials: H
authors.lastname: Cardoso-Cruz
authors.forename: Mafalda
authors.initials: M
authors.lastname: Sousa
authors.forename: Joana B
authors.initials: JB
authors.lastname: Vieira
authors.forename: Deolinda
authors.initials: D
authors.lastname: Lima
authors.forename: Vasco
authors.initials: V
authors.lastname: Galhardo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications* / Q000523:psychology; D001522:Behavior, Animal / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D005620:Freund's Adjuvant; D007719:Knee Joint; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000502:physiology*; D008569:Memory Disorders / Q000209:etiology* / Q000523:psychology*; D008570:Memory, Short-Term / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D010146:Pain / Q000150:complications* / Q000523:psychology; D017397:Prefrontal Cortex / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013028:Space Perception / Q000502:physiology*
chemical_list: D005620:Freund's Adjuvant
keywords: Inflammatory pain; Local field potentials; Mediodorsal thalamus; Spatial working memory; mPFC