Despite our extensive knowledge of the structure of negatively charged cell surface proteoglycans and sialoglycoconjugates in the brain, we have little understanding of how their negative charge contributes to brain function. We have previously shown that intensely photoluminescent 9-nm diameter quantum dots (QDs) with a CdSe core, a ZnS shell, and a negatively charged compact molecular ligand ...

Achievements made over the past few years have demonstrated the important role of the creatine and phosphocreatine system in the buffering and transport of high-energy phosphates into the brain; however, the non-energetic processes elicited by this guanidine compound in the hippocampus are still poorly understood. In the present study we disclosed that the incubation of rat hippocampal slices w...

Mice deficient in cholesterol 24-hydroxylase exhibit reduced rates of cholesterol synthesis and other non-sterol isoprenoids that arise from the mevalonate pathway. These metabolic abnormalities, in turn, impair learning in the whole animal and hippocampal long-term potentiation (LTP) in vitro. Here, we report pharmacogenetic experiments in hippocampal slices from wild-type and mutant mice that...

To explore the mechanism by which methohexital (MTH) activates epileptiform activity in patients with epilepsy, we examined the effects of MTH on hippocampal CA1 and neocortical neurons via extracellular and whole-cell patch-clamp recordings in rat brain slices. Perfusion of slices with 10 to 100 microM MTH caused no significant change in glutamatergic transmission in the hippocampal CA1 region...

We recently introduced an inducible pharmacogenetic approach where pharmacological manipulations can be used to reveal recessive mutant phenotypes in a temporally controlled manner. This approach takes advantage of synergisms between pharmacological and genetic manipulations to alter the function of specific signaling pathways. For example, mice heterozygous for a point mutation (T286A) in the ...

Matrix metalloproteinases (MMPs) are extracellular proteases that have well recognized roles in cell signaling and remodeling in many tissues. In the brain, their activation and function are customarily associated with injury or pathology. Here, we demonstrate a novel role for MMP-9 in hippocampal synaptic physiology, plasticity, and memory. MMP-9 protein levels and proteolytic activity are rap...

Laminar distribution of fiber systems is a characteristic feature of hippocampal organization. Ingrowing afferents, e.g. the fibers from the entorhinal cortex, terminate in specific layers, which implies the existence of laminar recognition cues. To identify cues that are involved in the laminar segregation of fiber systems in the hippocampus, we used an in vitro assay to study the adhesion of ...

Neuronal splice site selection events control multiple brain functions. Here, we report their involvement in stress-modulated hippocampal plasticity and errors of cognitive performance. Under stress, alternative splicing changes priority from synaptic acetylcholinesterase (AChE-S) to the normally rare, soluble and monomeric AChE-R variant, which facilitates hippocampal long-term potentiation (L...

Recently, several evolutionary conserved signaling pathways that play prominent roles in regulating early neurodevelopment have been found to regulate synaptic remodeling in the adult. To test whether adult neuronal expression of bone morphogenic protein (BMP) signaling components also plays a postnatal role in regulating neuronal plasticity, we modulated BMP signaling in mice both in vivo and ...

We have previously shown that nicotine, the addictive component of tobacco products, alters the blood-brain barrier (BBB) Na(+),K(+),2Cl(-) cotransporter (NKCC) during in vitro hypoxia-aglycemia exposure. Attenuation of abluminal NKCC suggests that accumulation of ions in the brain extracellular fluid would result in an increase of fluid or cytotoxic edema in the brain during hypoxia-aglycemia ...