Hippocampus shapes cortical sensory output and novelty coding through a direct feedback circuit.

To extract behaviorally relevant information from our surroundings, our brains constantly integrate and compare incoming sensory information with those stored as memories. Cortico-hippocampal interactions could mediate such interplay between sensory processing and memory recall1-4 but this remains to be demonstrated. Recent work parsing entorhinal cortex-to-hippocampus circuitry show its role in episodic memory formation5-7 and spatial navigation8. However, the organization and function of the hippocampus-to-cortex back-projection circuit remains uncharted. We combined circuit mapping, physiology and behavior with optogenetic manipulations, and computational modeling to reveal how hippocampal feedback modulates cortical sensory activity and behavioral output. Here we show a new direct hippocampal projection to entorhinal cortex layer 2/3, the very layer that projects multisensory input to the hippocampus. Our finding challenges the canonical cortico-hippocampal circuit model where hippocampal feedback only reaches entorhinal cortex layer 2/3 indirectly via layer 5. This direct hippocampal input integrates with cortical sensory inputs in layer 2/3 neurons to drive their plasticity and spike output, and provides an important novelty signal during behavior for coding objects and their locations. Through the sensory-memory feedback loop, hippocampus can update real-time cortical sensory processing, efficiently and iteratively, thereby imparting the salient context for adaptive learned behaviors with new experiences.

Hypervalent Iodonium Alkynyl Triflate Generated Phenylcyanocarbene and Its Reactivity with Aromatic Systems.

Phenylcyanocarbene was generated by the reaction of azide with a hypervalent iodonium alkynyl triflate and reacted in situ with 21 different carbocyclic and heterocyclic aromatic compounds. These reactions led to more complex products that frequently underwent subsequent rearrangements. The reactivity was further explored in a mechanistic study to ascertain the chemoselectivity and stereospecificity.

Formation and in situ reactions of hypervalent iodonium alkynyl triflates to form cyanocarbenes.

The conversion of readily available silylalkynes, iodobenzene diacetate, and azide anions was utilized to form and react cyanocarbenes. A copper(II)-catalyzed reaction was found to react in a different manner. Both of these methods benefit from the formation and in situ reaction of hypervalent iodonium alkynyl triflates in O-H insertion reactions.

Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase.

INTRODUCTION: The upregulation of cyclooxygenase (COX) expression by aldosterone (ALDO) or high salt diet intake is very interesting and complex in the light of what is known about the role of COX in renal function. Thus, in this study, we hypothesize that apocynin (APC) and/or eplerenone (EPL) inhibit ALDO/salt-induced kidney damage by preventing the production of prostaglandin E2 (PGE2). METHODS: Dahl salt-sensitive rats on either a low-salt or high-salt diet were treated with ALDO (0.2 mg pellet) in the presence of EPL (100 mg/kg/day) or APC (1.5 mM). Indirect blood pressure, prostaglandins and ALDO levels and histological changes were measured. RESULTS: Cyclooxygenase-2 (COX-2) levels were upregulated in the renal tubules and peritubular vessels after high-salt intake, and APC attenuated renal tubular COX-2 protein expression induced by ALDO. Plasma PGE2 levels were significantly reduced by ALDO in the rats fed a low-salt diet when compared to rats fed a high-salt diet. PGE2 was blocked by EPL but increased in the presence of APC. CONCLUSIONS: The beneficial effects of EPL may be associated with an inhibition of PGE2. The mechanism underlying the protective effects of EPL is clearly distinct from that of APC and suggests that these agents can have differential roles in cardiovascular disease.

Phytochemical induction of cell cycle arrest by glutathione oxidation and reversal by N-acetylcysteine in human colon carcinoma cells.

Cancer prevention by dietary phytochemicals has been shown to involve decreased cell proliferation and cell cycle arrest. However, there is limited understanding of the mechanisms involved. Previously, we have shown that a common effect of phytochemicals investigated is to oxidize the intracellular glutathione (GSH) pool. Therefore, the objective of this study was to evaluate whether changes in the glutathione redox potential in response to dietary phytochemicals was related to their induction of cell cycle arrest. Human colon carcinoma (HT29) cells were treated with benzyl isothiocyanate (BIT) (BIT), diallyl disulfide (DADS), dimethyl fumarate (DMF), lycopene (LYC) (LYC), sodium butyrate (NaB) or buthione sulfoxamine (BSO, a GSH synthesis inhibitor) at concentrations shown to cause oxidation of the GSH: glutathione disulfide pool. A decrease in cell proliferation, as measured by [(3)H]-thymidine incorporation, was observed that could be reversed by pretreatment with the GSH precursor and antioxidant N-acetylcysteine (NAC). Cell cycle analysis on cells isolated 16 h after treatment indicated an increase in the percentage (ranging from 75-30% for benzyl isothiocyanate and lycopene, respectively) of cells at G2/M arrest compared to control treatments (dimethylsulfoxide) in response to phytochemical concentrations that oxidized the GSH pool. Pretreatment for 6 h with N-acetylcysteine (NAC) resulted in a partial reversal of the G2/M arrest. As expected, the GSH oxidation from these phytochemical treatments was reversible by NAC. That both cell proliferation and G2/M arrest were also reversed by NAC leads to the conclusion that these phytochemical effects are also mediated, in part, by intracellular oxidation. Thus, one potential mechanism for cancer prevention by dietary phytochemicals is inhibition of the growth of cancer cells through modulation of their intracellular redox environment.