The channel of NMDA receptors is blocked by a wide variety of drugs. NMDA receptor channel blockers include drugs of abuse that induce psychotic behavior, such as phencyclidine, and drugs with wide therapeutic utility, such as amantadine and memantine. We describe here the molecular mechanism of amantadine inhibition. In contrast to most other described channel-blocking molecules, amantadine causes the channel gate of NMDA receptors to close more quickly. Our results confirm that amantadine binding inhibits current flow through NMDA receptor channels but show that its main inhibitory action at pharmaceutically relevant concentrations results from stabilization of closed states of the channel. The surprising variation in the clinical utility of NMDA channel blockers may in part derive from their diverse effects on channel gating.

If attention is divided during learning, memory suffers. Nevertheless, individuals can learn information with divided attention. This event-related functional magnetic resonance imaging (fMRI) study (n = 17) investigated what neural processes support (1) learning with divided attention and (2) retrieval of information learned with divided attention. Participants encoded words (Is the word abstract or concrete?) while performing an auditory discrimination task (press a button whenever an auditory pattern changes). The auditory task was easy or hard, depending on the similarity of the patterns. A behavioral study indicated that detailed ("recollective") information was more likely to be present for words encoded with the easy versus the hard concurrent task. Words encoded with the hard versus the easy concurrent task, in contrast, were more likely to rely on less detailed ("familiarity"-based) information. fMRI revealed encoding-related activation in the left prefrontal cortex (PFC) and left hippocampus that was linked to successful memory formation only for items encoded with the easy task. In contrast, activation in the right PFC and left parahippocampal gyrus was linked to successful memory for all items. Thus, successful encoding with the hard concurrent task was supported by a subset of the regions recruited for successful encoding with the easy task. The neural processes recruited for successful retrieval also depended on the encoding condition: The left PFC was disproportionately recruited for retrieval of items encoded with the easy task, whereas the right PFC was disproportionately recruited for retrieval of items encoded with the hard task. These findings may reflect left-sided specialization for recollective memories and right-sided specialization for familiarity-based traces.

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Motivated by devices such as the atomic force microscope, we compute the drag experienced by a cylindrical body of circular or rectangular cross-section oscillating at small amplitude near a plane wall. The body lies parallel to the wall and oscillates normally to it; the body is assumed to be long enough for the dominant flow to be two-dimensional. The flow is parameterized by a frequency parameter γ 2 (a Strouhal number) and the wall-body separation ∆ (scaled on body radius). Numerical solutions of the unsteady Stokes equations obtained using finite-difference computations in bipolar coordinates (for circular cross-sections) and boundary-element computations (for rectangular cross-sections) are used to determine the drag on the body. Numerical results are validated and extended using asymptotic predictions (for circular cylinders) obtained at all extremes of (γ, ∆)-parameter space. Regions in parameter space for which the wall has a significant effect on drag are identified.

Ligand