Reduction in the expression or function of [alpha]5-subunit-containing GABA[subscript A] receptors ([alpha]5GABA[subscript A]Rs) leads to improvement in several hippocampus-dependent memory domains. However, studies thus far mostly lack anatomical specificity in terms of neuronal circuits and populations. We demonstrate that mice with a selective…

Phosphorylation is a ubiquitous post-translational modification of proteins, and a known physiological regulator of K[superscript +] channel function. Phosphorylation of K[superscript +] channels by kinases has long been presumed to regulate neuronal processing and behavior. Although circumstantial evidence has accumulated from behavioral studies…

Pairs of rats foraged in trials either together or separately in an open field apparatus for pellets hidden in discreet locations in a 5 x 5 matrix. Trial duration was either 1 or 4 min. The tendency to choose locations that had earlier been visited by another rat was examined by comparing the choices made in the presence and absence of the other…

[alpha]CaMKII[superscript T286A] mutant mice lack long-term potentiation (LTP) in the hippocampal CA1 region and are impaired in spatial learning. In situ hybridization confirms that the mutant mice show the same developmental expression of [alpha]CaMKII as their wild-type littermates. A simple hypothesis would suggest that if LTP is a substrate…

The cAMP/PKA pathway plays a critical role in learning and memory systems in animals ranging from mice to "Drosophila" to "Aplysia." Studies of olfactory learning in "Drosophila" suggest that altered expression of either positive or negative regulators of the cAMP/PKA signaling pathway beyond a certain optimum range may be deleterious. Here we…

Gene transcription is required for long-term memory (LTM) formation. LTM formation is impaired in a male-specific manner in mice lacking either of the two Ca[superscript 2+] / calmodulin-dependent kinase kinase ("Camkk") genes. Since altered transcription was suggested to cause these impairments in LTM formation, we used microarrays to screen for…

We investigated the role of acetylcholine (ACh) during encoding and retrieval of tone/shock-induced fear conditioning with the aim of testing Hasselmo's cholinergic modulation model of encoding and retrieval using a task sensitive to hippocampal disruption. Lesions of the hippocampus impair acquisition and retention of contextual conditioning with…

A common cellular alteration, reduced post-burst afterhyperpolarization (AHP) in CA1 neurons, is associated with acquisition of the hippocampus-dependent tasks trace eyeblink conditioning and the Morris water maze. As a similar increase in excitability is correlated with these two learning paradigms, we sought to determine the interactive…

The Barnes maze is a spatial memory task that requires subjects to learn the position of a hole that can be used to escape the brightly lit, open surface of the maze. Two experiments assessed the relative importance of spatial (extra-maze) versus proximal visible cues in solving the maze. In Experiment 1, four groups of mice were trained either…

Little is known about signaling mechanisms underlying temporal associative learning. Here, we show that mice with a targeted point mutation that prevents autophosphorylation of [alpha]CaMKII ([alpha]CaMKII[superscript T286A]) learn trace eyeblink conditioning normally. This forms a sharp contrast to the severely impaired spatial learning in the…