Synaptic Reliability Correlates with Reduced Susceptibility to Synaptic Potentiation by Brain-Derived Neurotrophic Factor

Recent studies have implicated brain-derived neurotrophic factor (BDNF) in use-dependent modification of hippocampal synapses. BDNF can rapidly potentiate synaptic transmission at glutamatergic synapses by enhancing transmitter release. Using simultaneous perforated patch recording from pairs and triplets of glutamatergic hippocampal neurons, we have examined how the initial state of the glutamatergic synapse determines its susceptibility to synaptic modification by BDNF. We found that the degree of synaptic potentiation by BDNF depends on the initial reliability and strength of the synapse: Relatively weak connections were strongly potentiated, whereas the effect was markedly reduced at stronger synapses. The degree of BDNF-induced potentiation strongly correlated with the initial coefficient of variation (CV) of the amplitude of excitatory postsynaptic currents (EPSCs) and inversely correlated with the initial paired–pulse facilitation, suggesting that synapses with lower release probability (P_r) are more susceptible to the action of BDNF. To determine whether saturation of P_r could have masked the potentiation effect of BDNF in the stronger synapses, we lowered the initial P_r either by reducing the extracellular Ca²⁺ concentration ([Ca²⁺]_o) or by bath application of adenosine. Synapses that were initially strong remained unaffected by BDNF under these conditions of reduced P_r. Thus, the lack of BDNF effect on synaptic efficacy cannot simply be accounted for by saturation of P_r, but rather may be due to intrinsic changes associated with synaptic maturation that might covary with P_r. Finally, the dependence on initial synaptic strength was also found for divergent outputs of the same presynaptic neuron, suggesting that synaptic terminals with different degrees of responsiveness to BDNF can coexist within in the same neuron.     

Theoretical Medicine and Bioethics Index to Volume 20

Volume Contents

heoretical Medicine and Bioethics Index to Volume 20     

Familiarity and pronounceability of nouns and names

Ratings of familiarity and pronounceability were obtained from a random sample of 199 surnames (selected from over 80,000 entries in the Purdue University phone book) and 199 nouns (from the Ku?era-Francis, 1967, word database). The distributions of ratings for nouns versus names are substantially different: Nouns were rated as more familiar and easier to pronounce than surnames. Frequency and familiarity were more closely related in the proper name pool than the word pool, although both correlations were modest. Ratings of familiarity and pronounceability were highly related for both groups. A production experiment showed that rated pronounceability was highly related to the time taken to produce a name. These data confirm the common belief that there are differences in the statistical and distributional properties of words as compared to proper names. The value of using frequency and the ratings of familiarity and pronounceability for predicting variations in actual pronunciations of words and names are discussed.     

MESA: a new configuration for measuring electromagnetic field fluctuations

This paper describes how the multi-energy sensor array has been refitted to meet the needs of measuring geomagnetic and other types of electromagnetic phenomena in an environment. This portable laptop computer system was designed to measure the interaction of multiple frequencies with the psychological and physiological processes that underlie human exposure to electromagnetic fields across the spectra. New sensors and analytical software have been implemented in the new configuration.     

Drug discrimination under a concurrent fixed-ratio fixed-ratio schedule.

Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-ratio 10 fixed-ratio 40 schedule of food presentation, in which the fixed-ratio component with the lower response requirement was programmed to reinforce responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized, pigeons averaged 98% of their responses on the pentobarbital-biased key during training sessions preceded by pentobarbital, and they averaged 90% of their responses on the saline-biased key during training sessions preceded by saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, or ethanol, pigeons switched from responding on the saline-biased key at low doses to responding on the pentobarbital-biased key at higher doses (the dose-response curve was quantal). High doses of phencyclidine produced responding on both keys, whereas pigeons responded almost exclusively on the saline-biased key after all doses of methamphetamine. These and previous experiments using concurrent reinforcement schedules to study drug discrimination illustrate that the schedule of reinforcement is an important determinant of the shape of dose-effect curves in drug-discrimination experiments.     

A discrimination analysis of training-structure effects on stimulus equivalence outcomes.

Experiments designed to establish stimulus equivalence classes frequently produce differential outcomes that may be attributable to training structure, defined as the order and arrangement of baseline conditional discrimination training trials. Several possible explanations for these differences have been suggested. Here we develop a hypothesis based on an analysis of the simple simultaneous and successive discriminations embedded in conditional discrimination training and testing within each of the training structures that are typically used in stimulus equivalence experiments. Our analysis shows that only the comparison-as-node (many-to-one) structure presents all the simple discriminations in training that are subsequently required for consistently positive outcomes on all tests for the properties of equivalence. The sample-as-node (one-to-many) training structure does not present all the simple discriminations required for positive outcomes on either the symmetry or combined transitivity and symmetry (equivalence) tests. The linear-series training structure presents all the simple discriminations required for consistently positive outcomes on tests for symmetry, but not for symmetry and transitivity combined (equivalence) or transitivity alone. Further, the difference in the number of simple discriminations presented in comparison-as-node training versus the other training structures is larger when the intended class size is greater than three or the number of classes is larger than two. We discuss the relevance of this analysis to interpretations of stimulus equivalence research, as well as some methodological and theoretical implications.     

An examination of the effects of adult age on explicit and implicit learning of figural sequences

Memory for previously learned figural sequences and item-to-item covariations within figural sequences was examined under explicit and implicit instructional conditions in three age groups: young adults (17-23 years); middle-aged adults (35-45 years); and older adults (55-65 years). In Phase 1 of the experiment, the acquisition phase, half the subjects in each age group learned sequences of three to eight items in which the item-to-item changes conformed to an artificial grammar, and the other half of the subjects in each age group learned strings in which the item-to-item changes were nongrammatical. In Phase 2, the implicit/explicit test phase, subjects made forced-choice judgments about parts of the strings that they learned in Phase 1, under either explicit or implicit instructions. Analyses of Phase 2 data revealed that subjects in both instructional conditions used item-to-item covariations in making decisions about grammatical strings. However, use of previously learned covariations as well as the number of correct judgments about previously learned strings was greater in the explicit condition than in the implicit condition. An age-related deficit was found for explicit recognition of grammar-following sequences.     

Conflict Aversion: Preference for Ambiguity vs Conflict in Sources and Evidence

This research investigates preferences and judgments under ambiguous vs conflicting information. Three studies provided evidence for two major hypotheses: (1) Conflicting messages from two equally believable sources are dispreferred in general to two informatively equivalent, ambiguous, but agreeing messages from the same sources (i.e., conflict aversion); and (2) conflicting sources are perceived as less credible than ambiguous sources. Studies 2 and 3 yielded evidence for two framing effects. First, when the outcome was negative, subjects' preferences were nearly evenly split between conflict and ambiguity, whereas a positive outcome produced marked conflict aversion. Second, a high probability of a negative outcome or a low probability of a positive one induced conflict preference. However, no framing effects were found for source credibility judgments. Study 3 also investigated whether subject identification with a source might affect preferences or credibility judgments, but found no evi dence for such an effect. The findings suggest cognitive and moti vational explanations for conflict aversion as distinct from ambi guity aversion. The cognitive heuristic is that conflict raises suspicions about whether the sources are trustworthy or credi ble. The motivational explanation stems from that idea that if sources disagree, then the judge not only becomes uncertain but also must disagree with at least one of the sources, whereas if the sources agree then the judge may agree with them and only has to bear the uncertainty.