Selective and protracted effect of nifedipine on fear memory extinction correlates with induced stress response

Memory extinction, defined as a decrease of a conditioned response as a function of a non-reinforced conditioned stimulus presentation, has high biological and clinical relevance. Extinction is not a passive reversing or erasing of the plasticity associated with acquisition, but a novel, active learning process. Nifedipine blocks L-type voltage gated calcium channels (LVGCC) and has been shown previously to selectively interfere with the extinction, but not the acquisition, of fear memory. We studied here the effect of retrograde and anterograde shifts of nifedipine application, with respect to an extinction training, on the extinction of fear conditioning. Subcutaneous injection of 30 mg/kg nifedipine, at least up to 4 h before the extinction session, significantly impaired extinction, as did intraperitoneal injection of 15 mg/kg nifedipine, at least up to 2 h before extinction training. However, the injection of nifedipine also induced a strong and protracted stress response. The pharmacokinetics of nifedipine suggest that it was mainly this stress response that triggered the specific inhibition of extinction, not the blockade of LVGCC in the brain. Our results support recent findings that stress selectively interferes with the extinction, but not the acquisition, of fear memory. They also indicate that a pharmacological approach is not sufficient to study the role of brain LVGCC in learning and memory. Further research using specific genetically modified animals is necessary to delineate the role of LVGCC in fear memory extinction.     

Odor-specific habituation arises from interaction of afferent synaptic adaptation and intrinsic synaptic potentiation in olfactory cortex

Segmentation of target odorants from background odorants is a fundamental computational requirement for the olfactory system and is thought to be behaviorally mediated by olfactory habituation memory. Data from our laboratory have shown that odor-specific adaptation in piriform neurons, mediated at least partially by synaptic adaptation between the olfactory bulb outputs and piriform cortex pyramidal cells, is highly odor specific, while that observed at the synaptic level is specific only to certain odor features. Behavioral data show that odor habituation memory at short time constants corresponding to synaptic adaptation is also highly odor specific and is blocked by the same pharmacological agents as synaptic adaptation. Using previously developed computational models of the olfactory system we show here how synaptic adaptation and potentiation interact to create the observed specificity of response adaptation. The model analyzes the mechanisms underlying the odor specificity of habituation, the dependence on functioning cholinergic modulation, and makes predictions about connectivity to and within the piriform neural network. Predictions made by the model for the role of cholinergic modulation are supported by behavioral results.Filtering sensory input is critical for information processing tasks such as background segmentation, and shifting processing power away from redundant, stable, or repetitive stimuli toward dynamic, novel stimuli. A critical aspect of this filtering however, is stimulus specificity. Under most circumstances it may be most beneficial to selectively filter the redundant stimulus, while maintaining responsiveness to different, though perhaps highly similar stimuli.In the olfactory system, short-term habituation to stable or repeated odorants involves a metabotropic glutamate receptor (mGluR)-dependent depression of afferent synapses to the piriform cortex (Best and Wilson 2004). Blockade of group III mGluR receptors prevents cortical adaptation odors (Best and Wilson 2004), and reduces short-term habituation of odor-evoked reflexes (Best et al. 2005) and odor investigation (Yadon and Wilson 2005; Bell et al. 2008; McNamara et al. 2008). This short-term habituation is highly odor specific, with minimal cross-adaptation of piriform cortical single-unit responses or cross-habituation of behavioral responses to similar odors, including between mixtures and their components (Wilson 2000; Cleland et al. 2002). Interestingly, there is an experience-dependent component to short-term habituation odor specificity. The odor specificity is most pronounced for familiar odors, with very brief (<20 sec) exposure to odors producing more generalization, and longer exposures (>50 sec) sufficient to permit strong odor specificity in cortex adaptation (Wilson 2003).The homosynaptic nature of afferent synaptic depression underlying cortical adaptation (Wilson 1998; Best and Wilson 2004) may contribute to this odor specificity. However, the experience dependence suggests that there may be an additional process involved. In fact, theoretical views of piriform cortical function suggest that the cortex learns previous patterns of input via potentiation of intracortical association fiber synapses (Hasselmo et al. 1990; Barkai et al. 1994; Haberly 2001; Linster et al. 2003). This autoassociative process essentially creates a template of previous network activity, against which new input patterns can be compared, allowing enhanced discrimination between similar patterns, as well as completion of degraded patterns (Barkai et al. 1994; Barnes et al. 2008). In support of this hypothesis, previous work has demonstrated that disruption of normal synaptic potentiation in association fiber synapses through blockade of cholinergic muscarinic receptors (Patil et al. 1998; Linster et al. 2003), reduces odor specificity of cortical adaptation (Wilson 2001b), prevents the effects of odor experience on subsequent behavioral cross-habituation (Fletcher and Wilson 2002), and disrupts odor discrimination (Linster et al. 2001).The present series of studies further explored the role of combined afferent synaptic depression and intracortical association fiber synaptic potentiation on the specificity of cortical adaptation and odor habituation. Using a computational model of the olfactory system (Linster et al. 2007), the results suggest that activity-dependent association fiber plasticity is necessary to account for the specificity of odor habituation. Furthermore, in behavioral experiments blockade of cholinergic muscarinic receptors during habituation enhances generalization of odor habituation, consistent with the modeling and with previous electrophysiological results.     

Perceived behavioral changes in early multiple sclerosis

Acquired behavioral changes have essentially been described in advanced multiple sclerosis (MS). The present study was designed to determine whether behavioral modifications specifically related to the MS pathological process could be identified in the initial phase of the disease, as compared to control patients with chronic, relapsing and progressive inflammatory disorders not involving the central nervous system (CNS). Eighty-eight early MS patients (Expanded Disability Status Scale score 相似文献   

Einsatz von „virtuellen Realitäten“ in der Psychotherapie

The internet, as well as various mobile media (e.g. cellular phones, handhelds, mobile paddles) have proven very useful in supporting psychotherapeutic measures in various projects. Virtual reality technologies (VR) take technical as well as intervention possibilities a step further. They enable the creation of computer-based models of the real world, with which interaction via the human-machine interface is enabled. The three-dimensional and interactively explorable environment is predominately used for exposure treatment in the behavior therapy setting. The features of VR applications are utilized as a medium between imagined and in vivo confrontation. This article illustrates various applications and compiles findings regarding effectiveness. It is concluded that the exposure treatments using this technology for various described phobias have proven effective. The use of VR for treatment of other psychological illnesses, however, for example trauma disorders, as was demonstrated in the study at hand, is viewed very critically. Finally, research necessities are indicated and psychodynamic facets of VR are discussed.     

A lengthy look at the daily grind: time series analysis of events, mood, stress, and satisfaction

The present study investigated processes by which job stress and satisfaction unfold over time by examining the relations between daily stressful events, mood, and these variables. Using a Web-based daily survey of stressor events, perceived strain, mood, and job satisfaction completed by 14 university workers, 1,060 occasions of data were collected. Transfer function analysis, a multivariate version of time series analysis, was used to examine the data for relationships among the measured variables after factoring out the contaminating influences of serial dependency. Results revealed a contrast effect in which a stressful event associated positively with higher strain on the same day and associated negatively with strain on the following day. Perceived strain increased over the course of a semester for a majority of participants, suggesting that effects of stress build over time. Finally, the data were consistent with the notion that job satisfaction is a distal outcome that is mediated by perceived strain.     

Cholinergic modulation of learning and memory in the human brain as detected with functional neuroimaging

The advent of neuroimaging methods such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) has provided investigators with a tool to study neuronal processes involved in cognitive functions in humans. Recent years have seen an increasing amount of studies which mapped higher cognitive functions to specific brain regions. These studies have had a great impact on our understanding of neuroanatomical correlates of learning and memory in the living human brain. Recently, advances were made to go beyond the use of fMRI as a pure cognitive brain mapping device. One of these advances includes the use of psychopharmacological approaches in conjunction with neuroimaging. The paper will introduce the combination of neuroimaging and psychopharmacology as a tool to study neurochemical modulation of human brain function. A review of imaging studies using cholinergic challenges in the context of explicit and implicit learning and memory paradigms is provided which show that cholinergic neurotransmission modulates task-related activity in sensory and frontal cortical brain areas.     

Depression as measured by the Beck Depression Inventory-II among injecting drug users

This study conducts a confirmatory factor analysis of the Beck Depression Inventory-II (BDI-II) with a sample of 598 individuals who reported recent injecting drug use. Findings indicate that out of four models tested, the best model for this sample is a three-factor solution (somatic, affective, and cognitive) previously reported by Buckley, Parker, and Heggie. The findings that nearly 50% of participants provided BDI-II scores indicating significant depressive symptomatology reveals that these individuals are in need of treatment for their psychiatric symptoms as well as substance use. Somatic symptoms are endorsed more strongly than affective or cognitive symptoms of depression, suggesting a possible, but yet poorly defined, relationship between depressive symptomatology and drug use that centers on shared somatic symptomatology.     

The impact of response mode on implicit and explicit sequence learning

Evidence regarding the influence of response mode on sequence learning in serial reaction time (SRT) tasks has been mixed so far. In the present study, sequence learning was investigated under two different response conditions: manual (button presses) versus verbal (pronunciation of digits). Additionally, participants were divided post hoc into subgroups differing in their degree of explicit knowledge about the sequence. Results showed an interaction between response mode and type of learning (implicit vs. explicit), with explicit learning functioning more effectively under verbal than under manual conditions, whereas implicit learning was unaffected by the variation of the response mode. Implications concerning different underlying learning mechanisms (R-R learning vs. R-S learning) are discussed. Specifically, we suggest that the high response-effect distinctiveness of the verbal responses facilitated R-R learning.