The Role of Ease of Retrieval and Attribution in Memory Judgments: Judging Your Memory as Worse Despite Recalling More Events

Participants who had to recall 12 childhood events (a difficult task) were more likely to infer that they could not remember large parts of their childhood than participants who had to recall 4 events (an easy task), although the former recalled three times as many events. This pattern of results suggests that memory judgments are based on the experienced ease or difficulty of recall. Accordingly, the negative impact of recalling 12 events was attenuated when participants were led to attribute the experienced difficulty to the task rather than to the poor quality of their memory. The findings emphasize the role of subjective experiences and attribution in metamemory judgments.     

Different Training Procedures Recruit Either One or Two Critical Periods for Contextual Memory Consolidation, Each of Which Requires Protein Synthesis and PKA

We have used a combined genetic and pharmacological approach to define the time course of the requirement for protein kinase A (PKA) and protein synthesis in long-term memory for contextual fear conditioning in mice. The time course of amnesia in transgenic mice that express R(AB) and have genetically reduced PKA activity in the hippocampus parallels that observed both in mice treated with inhibitors of PKA and mice treated with inhibitors of protein synthesis. This PKA- and protein synthesis-dependent memory develops between 1 hr and 3 hr after training. By injecting the protein synthesis inhibitor anisomycin or the PKA inhibitor Rp-cAMPs at various times after training, we find that depending on the nature of training, contextual memory has either one or two brief consolidation periods requiring synthesis of new proteins, and each of these also requires PKA. Weak training shows two time periods of sensitivity to inhibitors of protein synthesis and PKA, whereas stronger training exhibits only one. These studies underscore the parallel dependence of long-term contextual memory on protein synthesis and PKA and suggest that different training protocols may recruit a common signaling pathway in distinct ways.     

The Specific Role of cGMP in Hippocampal LTP

Previous results have suggested that cGMP is involved in hippocampal long-term potentiation (LTP), perhaps as the presynaptic effector of a retrograde messenger. However, other studies have failed to replicate some of those results, making the role of cGMP uncertain. We therefore reexamined this question and identified several variables that can affect the contribution of cGMP. First, brief perfusion with 8-Br–cGMP before weak tetanic stimulation produced long-lasting potentiation in the CA1 region of hippocampal slices, but more prolonged perfusion with 8-Br–cGMP before the tetanus did not produce long-lasting potentiation. Second, the activity-dependent long-lasting potentiation by cGMP analogs was reduced when NMDA receptors were completely blocked, indicating that NMDA receptor activation contributes to, but is not required for, the potentiation. The amount of reduction of the potentiation differed with different protocols, and in some cases could be complete. Third, LTP produced by strong tetanic stimulation in the stratum radiatum of CA1 (which expresses eNOS) was blocked by inhibitors of soluble guanylyl cyclase or cGMP-dependent protein kinase, but LTP in the stratum oriens (which does not express eNOS) was not. The results of these experiments should help to explain some of the discrepant findings from previous studies, and, in addition, may provide insights into the mechanisms and functional role of the cGMP-dependent component of LTP.     

Contrasting Cortical Activity Associated with Category Memory and Recognition Memory

We collected functional neuroimaging data while volunteers performed similar categorization and recognition memory tasks. In the categorization task, volunteers first studied a series of 40 dot patterns that were distortions of a nonstudied prototype dot pattern. After a delay, while fMRI data were collected, they categorized 72 novel dot patterns according to whether or not they belonged to the previously studied category. In the recognition task, volunteers first studied five dot patterns eight times each. After a delay, while fMRI data were collected, they judged whether each of 72 dot patterns had been studied earlier. We found strikingly different patterns of brain activity in visual processing areas for the two tasks. During the categorization task, the familiar stimuli were associated with decreased activity in posterior occipital cortex, whereas during the recognition task, the familiar stimuli were associated with increased activity in this area. The findings indicate that these two types of memory have contrasting effects on early visual processing and reinforce the view that declarative and nondeclarative memory operate independently.     

Mushroom Bodies Suppress Locomotor Activity in Drosophila melanogaster

Locomotor activity of single, freely walking flies in small tubes is analyzed in the time domain of several hours. To assess the influence of the mushroom bodies on walking activity, three independent noninvasive methods interfering with mushroom body function are applied: chemical ablation of the mushroom body precursor cells; a mutant affecting Kenyon cell differentiation (mushroom body miniature¹); and the targeted expression of the catalytic subunit of tetanus toxin in subsets of Kenyon cells. All groups of flies with mushroom body defects show an elevated level of total walking activity. This increase is attributable to the slower and less complete attenuation of activity during the experiment. Walking activity in normal and mushroom body-deficient flies is clustered in active phases (bouts) and rest periods (pauses). Neither the initiation nor the internal structure, but solely the termination of bouts seems to be affected by the mushroom body defects. How this finding relates to the well-documented role of the mushroom bodies in olfactory learning and memory remains to be understood.     

Selective Abolition of the NMDA Component of Long-Term Potentiation in Mice Lacking mGluR5

The mechanisms underlying the differential expression of long-term potentiation (LTP) by AMPA and NMDA receptors, are unknown, but could involve G-protein-linked metabotropic glutamate receptors. To investigate this hypothesis we created mutant mice that expressed no metabotropic glutamate receptor 5 (mGluR5), but showed normal development. In an earlier study of these mice we analyzed field-excitatory postsynaptic potential (fEPSPs) in CA1 region of the hippocampus and found a small decrease; possibly arising from changes in the NMDAR-mediated component of synaptic transmission. In the present study we used whole-cell patch clamp recordings of evoked excitatory postsynaptic currents (EPSCs) in CA1 pyramidal neurons to identify the AMPAR- and NMDAR-mediated components of LTP. Recordings from control mice following tetanus, or agonist application (IS, 3R-1-amino-cyclopentane 1,3-dicarboxylic acid) (ACPD), revealed equal enhancement of the AMPA and NMDA receptor-mediated components. In contrast, CA1 neurons from mGluR5-deficient mice showed a complete loss of the NMDA-receptor-mediated component of LTP (LTP_NMDA), but normal LTP of the AMPA-receptor-mediated component (LTP_AMPA). This selective loss of LTP_NMDA was seen in three different genotypic backgrounds and was apparent at all holding potentials (−70 mV to +20 mV). Furthermore, the LTP_NMDA deficit in mGluR5 mutant mice could be rescued by stimulating protein kinase C (PKC) with 4β-phorbol-12,13-dibutyrate (PDBu). These results suggest that PKC may couple the postsynaptic mGluR5 to the NMDA-receptor potentiation during LTP, and that this signaling mechanism is distinct from LTP_AMPA. Differential enhancement of AMPAR and NMDA receptors by mGluR5 also supports a postsynaptic locus for LTP.     

Incurable suffering from the “hiatus theoreticus”? Some epistemological problems in modern medicine and the clinical relevance of philosophy of medicine

Up to now neither the question, whether all theoretical medical knowledge can at least be described as scientific, nor the one how exactly access to the existing scientific and theoretical medical knowledge during clinical problem-solving is made, has been sufficiently answered. Scientific theories play an important role in controlling clinical practice and improving the quality of clinical care in modern medicine on the one hand, and making it vindicable on the other. Therefore, the vagueness of unexplicit interrelations between medicine's stock of knowledge and medical practice appears as a gap in the theoretical concept of modern medicine which can be described as Hiatus theoreticus in the anatomy of medicine. A central intention of the paper is to analyze the role of philosophy of medicine for the clarification of the theoretical basis of medical practice. Clinical relevance and normativity in the sense of modern theory of science are suggested as criteria to establish a differentiation between philosophy of medicine as a primary medical discipline and the application of general philosophy in medicine.     

Effects of social context, reinforcer probability, and reinforcer magnitude on humans' choices to compete or not to compete.

In the first two experiments, subjects' choices to earn points (exchangeable for money) either by competing with a fictitious opponent or by not competing were studied. Buskist, Barry, Morgan, and Rossi's (1984) competitive fixed-interval schedule was modified to include a second response option, a noncompetitive fixed-interval schedule. After choosing to enter either option, the opportunity for reinforcers became available after the fixed-interval's duration had elapsed. Under the no-competition condition, points were always available after the interval had elapsed. Under the competition condition, points were available based on a predetermined probability of delivery. Experiments 1 and 2 examined how reinforcer probabilities and reinforcer magnitudes affected subjects' choices to compete. Several general conclusions can be made about the results: (a) Strong preferences to compete were observed at high and moderate reinforcer probabilities; (b) competing was observed even at very low reinforcer probabilities; (c) response rates were always higher in the competition component than in the no-competition component; and (d) response rates and choices to compete were insensitive to reinforcer-magnitude manipulations. In Experiment 3, the social context of this choice schedule was removed to determine whether the high levels of competing observed in the first two experiments were due to a response preference engendered by the social context provided by the experimenters through instructions. In contrast to the first two experiments, these subjects preferred the 60-s fixed-interval schedule (formerly the no-competition option), indicating that the instructions themselves were responsible for the preference to compete. This choice paradigm may be useful to future researchers interested in the effects of other independent variables (e.g., drugs, social context, instructions) on competitive behavior.     

Effects of delta 9-THC on marijuana smoking, dose choice, and verbal report of drug liking.

The effects of delta 9-tetrahydrocannabinol content of marijuana on cigarette smoking, dose choice, and verbal report of drug "liking" by adult males living in a residential laboratory were investigated. Marijuana cigarettes were available during programmed intervals while subjects were engaged in recreational activities. The tetrahydrocannabinol content of the cigarettes remained constant each day, but was changed across days. Subjects provided written ratings of drug liking at the end of each day. In the first study, placebo or active (2.3% delta 9-tetrahydrocannabinol) marijuana cigarettes were available for 1-, 2-, or 3-day intervals at varying times of day. The number of cigarettes smoked was unrelated to tetrahydrocannabinol content, although verbal reports of drug liking were consistently higher when marijuana cigarettes containing tetrahydrocannabinol were smoked. In a second study, a choice procedure, consisting of four 3-day blocks of 2 sample days and 1 choice day, was used. On sampling days, subjects smoked cigarettes varying in tetrahydrocannabinol content (0.0, 2.0, and 3.5%, w/w); on choice days they were allowed to choose between the two previously sampled doses. The number of cigarettes was not consistently related to tetrahydrocannabinol content. Ratings of drug liking were increased when marijuana cigarettes contained tetrahydrocannabinol, but ratings of marijuana containing 2.0% and 3.5% of the compound were similar. In contrast, subjects consistently chose the 3.5% dose over either the 0.0% or 2.0% dose. Dose choice was more sensitive to tetrahydrocannabinol content than either reports of drug liking or numbers of cigarettes smoked.