Olfactory learning-induced enhancement of the predisposition for LTP induction

Learning of a particularly difficult olfactory-discrimination (OD) task results in acquisition of rule learning. This enhancement in learning capability is accompanied by the long-term enhancement of synaptic connectivity between piriform cortex pyramidal neurons. In this study we examined whether olfactory rule learning would modify the predisposition to induce long-term potentiation (LTP) in the pathway projecting from the piriform cortex to the olfactory bulb. We report that OD learning was associated with enhancement in the predisposition to induce LTP. This learning-related effect may be affected by process generation of new granule cells located in the olfactory bulb.     

Persistent ERK activation maintains learning-induced long-lasting modulation of synaptic connectivity

Pyramidal neurons in the piriform cortex from olfactory-discrimination (OD) trained rats undergo synaptic modifications that last for days after learning. A particularly intriguing modification is reduced paired-pulse facilitation (PPF) in the synapses interconnecting these cells; a phenomenon thought to reflect enhanced synaptic release. The molecular machinery underlying this prolonged physiological modulation of synaptic connectivity is yet to be described. We have recently shown that extracellular regulated kinase (ERK) pathway and protein kinase C (PKC) are also required for learning-induced enhancement of intrinsic neuronal excitability. Here we examine whether these signal-transduction cascades are instrumental for the learning-induced, long-lasting PPF reduction. Days after learning completion, PD98059, a selective inhibitor of MEK, the upstream kinase of ERK, increased PPF in neurons from trained, but not in neurons from na?ve and pseudo-trained rats. Consequently, the differences in PPF between neurons from trained rats and controls were abolished. The level of activated ERK in synaptoneurosomes was significantly higher in piriform cortex samples prepared from trained rats. Notably, ERK activation revealed that PPF reduction lags behind ERK activation by 2 d. Similarly, the PKC blocker, GF-109203X, enhanced PPF in neurons from trained rats only, thus abolishing the differences between groups. Interestingly, the PKC activator, OAG, had no effect, indicating that PKC activation is required, but not sufficient for long-lasting PPF reduction. Our data show that persistent ERK activation has a key role in maintaining learning-induced PPF reduction for days. This time frame of compartmental ERK-dependent synaptic modulation suggests a novel role for ERK in cortical function.     

Long-term consolidation and retention of learning-induced tuning plasticity in the auditory cortex of the guinea pig.

The major goal of this study was to determine whether classical conditioning produces long-term neural consolidation of frequency tuning plasticity in the auditory cortex. Local field potentials (LFPs) were obtained from chronically implanted adult male Hartley guinea pigs that were divided into conditioning (n = 4) and sensitization control (n = 3) groups. Tuning functions were determined in awake subjects for average LFPs (approximately 0.4 to 36.0 kHz, -20 to 80 dB) immediately before training as well as 1 h and 1, 3, 7, and 10 days after training; sensitization subjects did not have a 10-day retention test. Conditioning consisted of a single session of 30 to 45 trials of a 6-s tone (CS, 70 dB) that was not the best frequency (BF, peak of a tuning curve), followed by a brief leg shock (US) at CS offset. Sensitization control animals received the same density of CS and US presentations unpaired. Heart rate recordings showed that the conditioning group developed conditioned bradycardia, whereas the sensitization control group did not. Local field potentials in the conditioning group, but not in the sensitization group, developed tuning plasticity. The ratio of responses to the CS frequency versus the BF were increased 1 h after training, and this increase was retained for the 10-day period of the study. Both tuning plasticity and retention were observed across stimulus levels (10-80 dB). Most noteworthy, tuning plasticity exhibited consolidation (i.e., developed greater CS-specific effects across retention periods), attaining asymptote at 3 days. The findings indicate that LFPs in the auditory cortex have three cardinal features of behavioral memory: associative tuning plasticity, long-term retention, and long-term consolidation. Potential cellular and subcellular mechanisms of LFP tuning plasticity and long-term consolidation are discussed.     

Treatment of a selectively mute third-grade child

A third-grade girl who did not speak in school was treated by school personnel using principles of behavior modification. A step-by-step procedure was designed which first encouraged speech in a one-to-one setting with an adult. Gradually elements of the regular school situation were introduced into the setting. The final phrase of treatment involved moving the elements back into the regular classroom. At the end of the school year, $\text{2}\text{1}\text{2}$ months following termination of treatment, the subject was still speaking freely.     

The nature of religious controls

Pastoral Psychology -     

Distinctive roles for amygdalar CREB in reconsolidation and extinction of fear memory

Cyclic AMP response element binding protein (CREB) plays a critical role in fear memory formation. Here we determined the role of CREB selectively within the amygdala in reconsolidation and extinction of auditory fear. Viral overexpression of the inducible cAMP early repressor (ICER) or the dominant-negative mCREB, specifically within the lateral amygdala disrupted reconsolidation of auditory fear memories. In contrast, manipulations of CREB in the amygdala did not modify extinction of fear. These findings suggest that the role of CREB in modulation of memory after retrieval is dynamic and that CREB activity in the basolateral amygdala is involved in fear memory reconsolidation.     

The ethics of selectively marketing the Health Maintenance Organization

Health Maintenance Organization (HMO) administrators have been accused of engaging in ‘selective marketing’. That is, through such strategies as tailoring the benefits package of the program or advertising in styles or in media that do not appeal to certain ‘undesirable’ audiences, the administrator can minimize the percentage of persons in the HMO who are heavy users of health care services. By means of analyzing what ‘insurance’ is (philosophically) and what it means for something to be a free market commodity, the author argues that, as long as American society chooses to regard health insurance as a commodity or service of the free market, the use of such strategies is within the moral rights of health administrators. The author concludes by noting some morally undesirable results of treating health insurance as a market commodity.     

Twenty-four hours of total sleep deprivation selectively impairs attentional networks

Performance decrements after sleep loss have been extensively studied and are usually attributed to generic attentional deficits. This claim, however, is based on the view of attention as a unitary construct, despite evidence that it should be considered a multidimensional cognitive ability. The aim of the present study was to evaluate the impact of one night of sleep deprivation on the efficiency of three attentional networks, defined by Posner and Raichle (1994) in anatomical and functional terms, as alerting, orienting, and executive control. Thirty participants performed the Attention Network Test at 9:00 a.m. following two different sleep conditions: baseline (a normal night of sleep) and deprivation (24 hrs of wakefulness). Results showed an overall slowing in reaction times and a significant decrease in accuracy after sleep deprivation. Sleep deprivation selectively affected the three attentional networks, given that only executive control efficacy significantly decreased after sleep deprivation. By contrast, phasic alerting and orienting showed no differences in the two sleep conditions. Thus, performance deficits following sleep deprivation do not reflect global attentional deficits.     

The direction of movement of machine controls

Experiments are described in which the relation between the direction of movement of a control and display was varied in order to determine what relationships are likely to cause least confusion to the operator of a machine. Two different types of task were used: a task consisting of intermittent stimuli whose rate of presentation could be varied, and a continuous pursuit task.

It is found that accuracy of performance varies with the degree of remoteiiess of the directional relationship from those met in everyday life, with the complexity of the task, with the ability of the subject, and there is some indication that under certain Conditions it may vary with the breadth of his attention. Awareness of the response aspect of the situation in these simple sensori-motor tasks, it is suggested, although necessary in the early stages of learning, may be associated in the later stages with confusion and error.     

Increasing CREB in the auditory thalamus enhances memory and generalization of auditory conditioned fear

Although the lateral nucleus of the amygdala (LA) is essential for conditioned auditory fear memory, an emerging theme is that plasticity in multiple brain regions contributes to fear memory formation. The LA receives direct projections from the auditory thalamus, specifically the medial division of the medial geniculate nucleus (MGm) and adjacent posterior intralaminar nucleus (PIN). While traditionally viewed as a simple relay structure, mounting evidence implicates the thalamus in diverse cognitive processes. We investigated the role of plasticity in the MGm/PIN in auditory fear memory. First we found that auditory fear conditioning (but not control manipulations) increased the levels of activated CREB in both the MGm and PIN. Next, using viral vectors, we showed that exogenously increasing CREB in this region specifically enhanced formation of an auditory conditioned fear memory without affecting expression of an auditory fear memory, formation of a contextual fear memory, or basic auditory processing. Interestingly, mice with increased CREB levels in the MGm/PIN also showed broad auditory fear generalization (in contrast to control mice, they exhibited fear responses to tones of other frequencies). Together, these results implicate CREB-mediated plasticity in the MGm/PIN in both the formation and generalization of conditioned auditory fear memory. Not only do these findings refine our knowledge of the circuitry underlying fear memory but they also provide novel insights into the neural substrates that govern the degree to which acquired fear of a tone generalizes to other tones.     

Evidence of mnemonic ability selectively affecting truthful and deceptive response dynamics

In the executive model of deception, the telling of a lie necessitates the inhibition of a veridical prepotent response (the truth), and such inhibition incurs a temporal penalty, manifest as a longer response time. If memory processes are engaged in generating such truths, then memory function should affect truthful and deceptive response times. To investigate this we examined the relationship between performance on a semantic knowledge deception task and a test of verbal memory in 40 college students. We found that verbal memory performance differentially affects the temporal parameters of truth and deception.     

Foreground contextual fear memory consolidation requires two independent phases of hippocampal ERK/CREB activation

Fear conditioning is a popular model for investigating physiological and cellular mechanisms of memory formation. In this paradigm, a footshock is either systematically associated to a tone (paired conditioning) or is pseudorandomly distributed (unpaired conditioning). In the former procedure, the tone/shock association is acquired, whereas in the latter procedure, the context/shock association will prevail. Animals with chronically implanted recording electrodes show enhanced amplitude of the extracellularly recorded field EPSP in CA1 pyramidal cells for up to 24 h after unpaired, but not paired, fear conditioning. This is paralleled by a differential activation of the ERK/CREB pathway in CA1, which is monophasic in paired conditioning (0-15 min post-conditioning), but biphasic (0-1 h and 9-12 h post-conditioning) in unpaired conditioning as revealed by immunocytochemistry and Western blotting. Intrahippocampal injection of the MEK inhibitor U0126 prior to each phase prevents the activation of both ERK1/2 and CREB after unpaired conditioning. Block of any activation phase leads to memory impairment. We finally reveal that the biphasic activation of ERK/CREB activity is independently regulated, yet both phases are critically required for the consolidation of long-term memories following unpaired fear conditioning. These data provide compelling evidence that CA1 serves different forms of memory by expressing differential cellular mechanisms that are dependent on the training regime.     

Enhancement of perceptual sensitivity as the result of selectively attending to spatial locations

The present experiment employed a visual signal-detection task within a cost-benefit (inhibition-facilitation) paradigm to examine the effects of selective attention on perceptual sensitivity. A central cue directed the subjects’ attention to either a right or a left spatial location where a detection task was performed. The cue was either a high/low or neutral-validity indicator of the position in which an event was likely to occur. A rating-scale response scheme in conjunction with the subjects’ target signal locational judgments allowed for the construction of ROC curves for each condition. Significant benefits were found for all subjects, supporting the hypothesis that selective attention can enhance perceptual sensitivity. Deallocation of attention resulted in an inhibition of sensitivity in unattended spatial locations. Subjects were consistently most sensitive in the right spatial location. There were no significant differences in overall response bias among the three conditions or in spatial locations. The results support theories of attention, such as “perceptual tuning, ” that suggest very early selective control.     

Effects of attending selectively to the spatial position of reflex-eliciting and reflex-modulating stimuli

The question of whether automatic, sensory processes can be modified by selectively directing attention to stimuli was addressed by comparing effects on brainstem reflexes that share a common efferent pathway but have distinct afferent limbs. Subjects judged the duration of brief but intense blink-eliciting tones (Experiment 1) or weak tones preceding a blink-eliciting air puff at interstimulus intervals producing blink inhibition (Experiment 2). Tones occurred unpredictably at left, right, or midline loci; designation of the target location varied across blocks of trials. Latency of blinks to lateralized blink-eliciting targets was facilitated selectively, and the magnitude of blinks evoked by air puff following lateralized prestimulus targets was inhibited selectively. There was no evidence for a midline selective effect. Results appear to support a preset differential processing of stimuli in sensory pathways at low, possibly subcortical, levels and the consequent modification of obligatory, automatic processes.