Depotentiation of vdccLTP Requires NMDAR Activation

Long-term potentiation is an enduring increase in synaptic efficacy following repeated stimulation of afferent fibers that is thought to underlie memory. In area CA1 of the hippocampus at least two forms of synaptic potentiation coexist at the same synapses; nmdaLTP and vdccLTP. NmdaLTP is induced by Ca2+ entry through NMDARs and is dependent on serine/threonine kinase activation, while vdccLTP is induced through Ca2+ entry through VDCCs and is dependent on tyrosine kinase activation. Depotentiation is a mechanism known to reverse nmdaLTP through phosphatase activation. The depotentiation of vdccLTP has not been previously investigated. We used hippocampal slices (area CA1) from male Long-Evans rats to induce vdccLTP with a 200-Hz tetanus in the presence of 50 microM APV. The 200-Hz tetanus resulted in a slowly developing vdccLTP that remained stable for at least 30 min. Thirty minutes after vdccLTP was induced, a low-frequency tetanus (3, 10, 20, 30, or 40 Hz) was applied in the presence of APV in an attempt to depotentiate vdccLTP. The 3- and 10-Hz low-frequency tetani resulted in no depotentiation. The 20- and 30-Hz tetani partially depotentiated vdccLTP (by approximately 13%), whereas the 40-Hz tetanus resulted in further potentiation. When APV was washed out prior to the 3-Hz low-frequency tetanus, the vdccLTP was completely depotentiated--presumably by NMDAR mechanisms. Our results indicate that vdccLTP is resistant to depotentiation under low-frequency stimulation conditions that readily depotentiate nmdaLTP. As tetanus frequencies are increased a small depotentiation is observed, suggesting that vdccLTP can be depotentiated to a small extent. When NMDARs are unblocked, vdccLTP can be completely depotentiated by a 3-Hz low-frequency tetanus, suggesting that vdccLTP can be depotentiated via activation of NMDAR mechanisms.     

Alzheimer amyloid beta-peptide inhibits the late phase of long-term potentiation through calcineurin-dependent mechanisms in the hippocampal dentate gyrus

The perforant path projecting from the entorhinal cortex to the hippocampal dentate gyrus is a particularly vulnerable target to the early deposition of amyloid beta (Abeta) peptides in Alzheimer's brain. The authors previously showed that brief applications of Abeta at subneurotoxic concentrations suppressed the early-phase long-term potentiation (E-LTP) in rat dentate gyrus. The current study further examines the effect of Abeta on the late-phase LTP (L-LTP) in this area. Using multiple high-frequency stimulus trains, a stable L-LTP lasting for at least 3 h was induced in the medial perforant path of rat hippocampal slices. Bath application of Abeta(1-42) (0.2-1.0 microM) during the induction trains attenuated both the initial and late stages of L-LTP. On the other hand, Abeta(1-42) perfusion within the first hour following the induction primarily impaired the late stage of L-LTP, which resembled the action of the protein synthesis inhibitor emetine. Blockade of calcineurin activity with FK506 or cyclosporin A completely prevented Abeta-induced L-LTP deficits. These results suggest that Abeta(1-42) impaired both the induction and maintenance phase of dentate L-LTP through calcineurin-dependent mechanisms. In the concentration range effective for inhibiting L-LTP, Abeta(1-42) also reduced the amplitude of NMDA receptor-mediated synaptic currents in dentate granule cells via a postsynaptic mechanism. In addition, concurrent applications of Abeta(1-42) with the protein synthesis inhibitor caused no additive reduction of L-LTP, indicating a common mechanism underlying the action of both. Thus, inhibition of NMDA receptor channels and disruption of protein synthesis were two possible mechanisms contributing to Abeta-induced L-LTP impairment.     

Variable-interval reinforcement schedule value influences responding following REM sleep deprivation

The effects of rapid-eye movement sleep deprivation (REMSD) in rats were studied in relation to variable-interval (VI) reinforcement schedule value. Initially, lever pressing was maintained on a VI 30-s schedule of food pellet delivery. After a baseline was established, rats were repeatedly exposed to 96 hr of REMSD and control conditions of an equivalent duration. Responding decreased following REMSD but not after exposure to control conditions. Lever pressing was then maintained on a VI 15-s schedule of food pellet delivery and exposure to the REMSD and control conditions was repeated. Under this condition following repeated REMSD exposures, rates of lever pressing became similar to baseline responding. A VI 30-s schedule of food pellet delivery was then reinstated and REMSD and control conditions were repeated. Lever pressing following exposure to the REMSD condition decreased for 3 of 4 rats. Results suggest that VI schedule value influences the effects of REMSD on responding.     

Preference reversals with food and water reinforcers in rats

Rats were given a choice between a smaller, immediately available reward and a larger reward available after a delay. In one phase, the reward was food and in another phase, the reward was water. Constant delays were added between the choice presentation and the delivery of the reward alternatives. As the time between choice and reward delivery increased from 0 to 25 s, all rats (except one in the water phase) reversed their preference from the smaller, sooner alternative to the larger, later alternative. These findings extend the generality of the preference-reversal animal model to qualitatively different reinforcers. Furthermore, the presence of both impulsive and self-control choices within the same animal is consistent with the view that self-control may be understood as choice behavior, and that species differences in self-control may be differences in degree, not kind.     

Human concurrent performances: The effects of experience, instructions, and schedule-correlated stimuli

In order to investigate the effects of separate exposures to single schedules, of unique schedule-correlated stimuli, and of independency-informing instructions upon choice under concurrent variable-interval schedules, 28 human subjects were divided into eight groups. Each subject was exposed to a baseline procedure, an experimental procedure, and a return to the baseline procedure. Different combinations of these three manipulations were applied to the different groups only during the experimental phase (except for the independency-informing instructions, which were given to half of the groups at the start of training). For the group of subjects exposed to the combination of all three manipulations, the logarithms of the ratios of response frequencies tended to be linearly related to the logarithms of the ratios of reinforcement frequencies during the experimental phase. These orderly effects were not obtained with subjects in the other groups. The results suggest that human choice was well described by the generalized matching law when the three manipulations were simultaneously in effect, and that unreported differences in the use of these three procedural variables might partly account for contradictions between results in previous studies of human concurrent performance.     

A Computational Model of Linguistic Humor in Puns

Humor plays an essential role in human interactions. Precisely what makes something funny, however, remains elusive. While research on natural language understanding has made significant advancements in recent years, there has been little direct integration of humor research with computational models of language understanding. In this paper, we propose two information‐theoretic measures—ambiguity and distinctiveness—derived from a simple model of sentence processing. We test these measures on a set of puns and regular sentences and show that they correlate significantly with human judgments of funniness. Moreover, within a set of puns, the distinctiveness measure distinguishes exceptionally funny puns from mediocre ones. Our work is the first, to our knowledge, to integrate a computational model of general language understanding and humor theory to quantitatively predict humor at a fine‐grained level. We present it as an example of a framework for applying models of language processing to understand higher level linguistic and cognitive phenomena.     

High-strain induced reverse martensitic transformation in an ultrafine-grained Ti-Nb-Ta-Zr alloy

We report on a novel phenomenon, that is a high-strain-induced reverse martensitic transformation in an ultrafine-grained Ti–36Nb–2Ta–3Zr (wt.%) alloy processed by equal channel angular pressing (ECAP) at room temperature. Our results show that a martensitic transformation from body-centred cubic β matrix to orthorhombic α″ martensite occurs under low-strain ECAP conditions and that a large portion (~34%) of martensite transforms into a matrix phase (i.e. reverse martensitic transformation) with increasing ECAP strain to a high value of 4 (i.e. 6 passes) with a corresponding reduction in the α″-lath thickness and a refinement of grain size in the matrix phase.     

Is systemic reform in education morally justifiable?

Systemic education reform calls for state imposition of uniform standards for student performance, the curriculum, and student opportunities to learn that curriculum, coupled with the alignment of basic state accountability, teacher education, and financing policies and expanded school decision-making authority. Proponents argue that systemic reform will have the effect of enhancing overall economic growth and equalizing opportunities for the most disadvantaged. Analysis of the first claim suggests that the inherent tension between employment-oriented outcome standards and discipline-oriented curriculum frameworks and the uniform application of such standards to all schools may undermine economic growth. Moreover, systemic reform appears more likely to transform current social inequalities than to eliminate them.     

Polydipsia induced in rats by second-order schedules of reinforcement.

Three rats were exposed to a second-order schedule in which fixed-interval components ended either with food or with a brief stimulus that was never paired with food. Food and the brief stimulus occurred in a random sequence (variable-ratio 2 overall schedule). Another three rats were exposed to a similar second-order schedule, the only difference being that the food or the stimulus was presented independently of operant behavior (fixed-time components). The three rats exposed to the fixed-interval components licked at a water spout after each food presentation. These rats also licked in the intervals after the brief stimulus. Although the discriminative properties of food and of the brief stimulus were identical in relation to subsequent reinforcement, licking after the stimulus was less than after food. The three rats exposed to the second-order schedules with fixed-time components also licked at the water spout after food, but these rats did not lick consistently after brief stimulus presentations.