Do spatial and recognition memories have a lateralized processing by the dorsal hippocampus CA3?

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that exist in three isoforms: PPARα, PPARβ/δ and PPARγ. Studies suggest that the PPAR signalling system may modulate pain, anxiety and cognition. The aim of the present study was to investigate whether endogenous signalling via PPARs differentially modulates innate anxiety responses and mnemonic function in the presence and absence of inflammatory pain. We examined the effects of intraperitoneal administration of GW6471 (PPARα antagonist), GSK0660 (PPARβ/δ antagonist), GW9662 (PPARγ antagonist), and N-palmitoylethanolamide (PEA) on rat behaviour in the elevated plus maze (EPM), open field (OF), light-dark box (LDB), and novel object recognition (NOR) tests in the presence or absence of chronic inflammatory pain. Complete Freund’s Adjuvant (CFA)-injected rats exhibited impaired recognition and spatial mnemonic performance in the NOR test and pharmacological blockade of PPARα further impaired spatial memory in CFA-treated rats. N-oleoylethanolamide (OEA) levels were higher in the dorsal hippocampus in CFA-injected animals compared to their counterparts. The results suggest a modulatory effect of CFA-induced chronic inflammatory pain on cognitive processing, but not on innate anxiety-related responses. Increased OEA-PPARα signalling may act as a compensatory mechanism to preserve spatial memory function following CFA injection.

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Prenatally traumatized mice reveal hippocampal methylation and expression changes of the stress-related genes Crhr1 and Fkbp5

Translational Psychiatry ◽

10.1038/s41398-021-01293-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anne-Christine Plank ◽

Stefan Frey ◽

Lukas Andreas Basedow ◽

Jalal Solati ◽

Fabio Canneva ◽

...

Keyword(s):

Stress Reactivity ◽

Dorsal Hippocampus ◽

Methylation Status ◽

Stress Axis ◽

Mrna Levels ◽

Fk506 Binding Protein ◽

Adult Mice ◽

Stress Related Genes ◽

Long Term Impact

AbstractIn our previous study, we found that prenatal trauma exposure leads to an anxiety phenotype in mouse pups, characterized by increased corticosterone levels and increased anxiety-like behavior. In order to understand the mechanisms by which aversive in utero experience leads to these long-lasting behavioral and neuroendocrine changes, we investigated stress reactivity of prenatally traumatized (PT) mice, as well as the expression and methylation levels of several key regulatory genes of the stress axis in the dorsal hippocampus (dHPC) of the PT embryo and adult mice. We detected increased corticotropin-releasing hormone receptor 1 (Crhr1) and decreased FK506 binding protein 5 (Fkbp5) mRNA levels in the left dHPC of adult PT mice. These alterations were accompanied by a decreased methylation status of the Crhr1 promoter and an increased methylation status of the Fkbp5 promoter, respectively. Interestingly, the changes in Fkbp5 and Crhr1 mRNA levels were not detected in the embryonic dHPC of PT mice. Together, our findings provide evidence that prenatal trauma has a long-term impact on stress axis function and anxiety phenotype associated with altered Crhr1 and Fkbp5 transcripts and promoter methylation.

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Robust information routing by dorsal subiculum neurons

Science Advances ◽

10.1126/sciadv.abf1913 ◽

2021 ◽

Vol 7 (11) ◽

pp. eabf1913

Author(s):

Takuma Kitanishi ◽

Ryoko Umaba ◽

Kenji Mizuseki

Keyword(s):

Nucleus Accumbens ◽

Large Scale ◽

Dorsal Hippocampus ◽

Retrosplenial Cortex ◽

Projection Neurons ◽

Target Region ◽

Ca1 Neurons ◽

Axonal Projections ◽

Output Structure ◽

Hippocampal Ca1

The dorsal hippocampus conveys various information associated with spatial navigation; however, how the information is distributed to multiple downstream areas remains unknown. We investigated this by identifying axonal projections using optogenetics during large-scale recordings from the rat subiculum, the major hippocampal output structure. Subicular neurons demonstrated a noise-resistant representation of place, speed, and trajectory, which was as accurate as or even more accurate than that of hippocampal CA1 neurons. Speed- and trajectory-dependent firings were most prominent in neurons projecting to the retrosplenial cortex and nucleus accumbens, respectively. Place-related firing was uniformly observed in neurons targeting the retrosplenial cortex, nucleus accumbens, anteroventral thalamus, and medial mammillary body. Theta oscillations and sharp-wave/ripples tightly controlled the firing of projection neurons in a target region–specific manner. In conclusion, the dorsal subiculum robustly routes diverse navigation-associated information to downstream areas.

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