Impairments in fear conditioning in mice lacking the nNOS gene

The fear conditioning paradigm is used to investigate the roles of various genes, neurotransmitters, and substrates in the formation of fear learning related to contextual and auditory cues. In the brain, nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) functions as a retrograde neuronal messenger that facilitates synaptic plasticity, including the late phase of long-term potentiation (LTP) and formation of long-term memory (LTM). Evidence has implicated NO signaling in synaptic plasticity and LTM formation following fear conditioning, yet little is known about the role of the nNOS gene in fear learning. Using knockout (KO) mice with targeted mutation of the nNOS gene and their wild-type (WT) counterparts, the role of NO signaling in fear conditioning was investigated. Plasma levels of the stress hormone corticosterone were measured to determine the relationship between physiological and behavioral response to fear conditioning. Contextual fear learning was severely impaired in male and female nNOS KO mice compared with WT counterparts; cued fear learning was slightly impaired in nNOS KO mice. Sex-dependent differences in both contextual and cued fear learning were not observed in either genotype. Deficits in contextual fear learning in nNOS KO mice were partially overcome by multiple trainings. A relationship between increase in plasma corticosterone levels following footshock administration and the magnitude of contextual, but not cued freezing was also observed. Results suggest that the nNOS gene contributes more to optimal contextual fear learning than to cued fear learning, and therefore, inhibition of the nNOS enzyme may ameliorate context-dependent fear response.Anxiety disorders, such as post-traumatic stress disorder (PTSD), constitute the most prevalent mental illnesses in the United States, costing nearly one-third of the country''s total health bill (Greenberg et al. 1999). The treatment of these disorders requires overcoming complications such as reluctance to seek mental health treatment and an extremely high comorbidity rate with other affective disorders, reaching 80% (Brady 1997; Solomon and Davidson 1997). Emerging evidence suggests that dysfunctions underlying acquired anxiety and PTSD include an abnormal reaction to stress, which is mediated by specific neurochemical and neuroanatomical substrates (Yehuda and McFarlane 1995; Adamec 1997). Pharmacotherapies that target neuronal signaling molecules, such as nitric oxide (NO), may play a role in the treatment of these disorders.In the brain, N-methyl-d-aspartate receptor (NMDAR) activation and calcium influx into the cell activates the neuronal nitric oxide synthase (nNOS) enzyme to produce NO, which has the role of retrograde messenger (Snyder 1992). NO is involved in memory formation and synaptic plastic events such as late-phase long-term potentiation (LTP) (Lu et al. 1999; Arancio et al. 2001; Puzzo et al. 2006). Behavioral evidence in invertebrates (Lewin and Walters 1999; Muller 2000; Kemenes et al. 2002; Matsumoto et al. 2006) and vertebrates (Medina and Izquierdo 1995; Rickard et al. 1998; Ota et al. 2008) suggest that NO has a major role in consolidation of long-term memory (LTM). Recently, studies have shown that site-specific pharmacological blockade of NO signaling in rats impairs contextual (Resstel et al. 2008) and cued (Schafe et al. 2005) fear learning. However, the role of the nNOS gene in fear conditioning has not been investigated.In the present study, fear conditioning was investigated in homozygous nNOS knockout (KO) and wild-type (WT) mice. In the fear-conditioning paradigm, the association of a footshock (unconditioned stimulus; US), with a specific context and a neutral stimulus (auditory cue) results in learned fear. Re-exposure to the conditioning context and to the previously neutral auditory cue (conditioned stimulus; CS) elicits a freezing response in the absence of the aversive US. Thus, the fear-conditioning paradigm includes both contextual and cued fear learning components, which can be measured in separate tests. Fear conditioning recruits both the amygdala (emotional cue learning) and the hippocampus (spatial/contextual learning) (Phillips and LeDoux 1992; Goosens and Maren 2004; Mei et al. 2005). The involvement of these brain regions in fear learning and anxiety has been confirmed by animal and human imaging studies (LeDoux 1998; Rauch et al. 2006).We report that nNOS KO mice showed a severe deficiency in contextual fear learning and a less marked deficit in cued fear learning compared with WT mice after a single fear-conditioning session. This deficiency was partially improved by multiple (four) fear-conditioning sessions. In addition, we observed that plasma levels of corticosterone, the primary stress hormone in rodents, are related to contextual fear learning ability.     

The Balance of Power: Effects of Role and Market Forces on Negotiated Outcomes1

Role and market forces provide two sources of power that affect negotiated outcomes. To test their effects, 48 subjects participated in one of two negotiation markets that favored either buyers or sellers. Profit was influenced by both power sources: Buyers outperformed sellers, and negotiators in a favorable market outperformed negotiators in an unfavorable market. This effect was shown to be additive, indicating that the effects of the two sources of power were independent of one another. Whereas negotiators advantaged by market forces showed increases in profit over time, profits for negotiators disadvantaged by the market remained stable. Joint profit rose throughout both markets. However, this did not reflect increasing integrativeness in the markets; rather, the increase could be attributed to increases in high power negotiator profits. Markets became more distributive over time, and both the effectiveness and efficiency of bargaining decreased, particularly in the market favoring buyers.     

Physiological correlates of intellectual function in children with sickle cell disease: hypoxaemia, hyperaemia and brain infarction

Lowered intelligence relative to controls is evident by mid-childhood in children with sickle cell disease. There is consensus that brain infarct contributes to this deficit, but the subtle lowering of IQ in children with normal MRI scans might be accounted for by chronic systemic complications leading to insufficient oxygen delivery to the brain. We investigated the relationship between daytime oxyhaemoglobin saturation (SpO2), cerebral blood flow velocity (CBFV) and intellectual function (IQ) using path-analysis in 30 adolescents with sickle cell disease (mean age 17.4 years, SD 4.2). Initial analyses revealed that the association between SpO2 and Full Scale IQ (FSIQ) was fully mediated by increased CBFV, whereby SpO2 was negatively correlated with CBFV and CBFV was negatively correlated with FSIQ, i.e. decreases in oxygen saturation are associated with increases in velocity, and increased velocity is associated with lowered IQ scores. The mediated relationship suggests that lowered IQ may be a function of abnormal oxygen delivery to the brain. Further analyses showed that the association between CBFV and IQ was significant for verbal but not for performance IQ. The pathophysiology characteristic of SCD can interfere with brain function and constrain intellectual development, even in the absence of an infarct. This supports the hypothesis that lowered intellectual function is partly explained by chronic hypoxia, and has wider implications for our understanding of SCD pathophysiology.     

Electrophysiological indices of brain activity to "the" in discourse

In a first experiment, we recorded event-related-potentials (ERPs) to "the" followed by meaningful words (Story) versus "the" followed by nonsense syllables (Nonse). Left and right lateral anterior positivities (LAPs) were seen from the onset of "the" up to 200 ms in both conditions. Later than 200 ms following the onset of "the", the left and right LAPs continued for "the" in the Story, but were replaced by a negativity in the Nonse Condition. In a second experiment, ERPs were recorded to "the" in the Story and Nonse contexts mixed together under two different task instructions (attend to the auditory stimuli versus ignore the auditory stimuli). The same pattern of findings as Experiment 1 were observed for the Story and Nonse contexts when the participants attended to the auditory stimuli. Ignoring the auditory stimuli led to an attenuation of the right LAP, supporting the hypothesis that it is an index of discourse processing.     

Goal-directed memory: the role of cognitive control in older adults' emotional memory

The present study revealed that older adults recruit cognitive control processes to strengthen positive and diminish negative information in memory. In Experiment 1, older adults engaged in more elaborative processing when retrieving positive memories than they did when retrieving negative memories. In Experiment 2, older adults who did well on tasks involving cognitive control were more likely than those doing poorly to favor positive pictures in memory. In Experiment 3, older adults who were distracted during memory encoding no longer favored positive over negative pictures in their later recall, revealing that older adults use cognitive resources to implement emotional goals during encoding. In contrast, younger adults showed no signs of using cognitive control to make their memories more positive, indicating that, for them, emotion regulation goals are not chronically activated.     

Why do women underperform under stereotype threat? Evidence for the role of negative thinking

This study investigated the role of negative thinking as a potential mediator of performance deficits under stereotype threat. After being assigned to a stereotype-threat or a no-threat condition, 60 female participants were asked to complete a difficult math task. Using the thought-listing technique, women under stereotype threat reported a higher number of negative thoughts specifically related to the test and to mathematics compared with women in the no-threat condition. Moreover, women under stereotype threat also showed a sharp decrease in performance that (a) was most pronounced in the second half of the test and (b) was mediated by the increase in negative thinking.     

COVID-19-related threat perceptions,political identity,and voting in the 2020 presidential election

Perceptions of the COVID-19 virus varied drastically in the United States, with many people highly concerned by health-related consequences (realistic threats) and many others concerned by sociocultural implications (symbolic threats). Across three studies, we tested whether differing realistic and symbolic COVID-19 related threat perceptions varied along gender and political identity near the 2020 US Presidential Election. In all three studies, we found that realistic COVID-19 related threat perceptions were positively associated with a liberal political identity; this pattern did not vary by gender. In Studies 1 and 3, symbolic COVID-19 related threat perceptions were positively associated with a conservative political identity and also did not vary by gender. In Study 2, however, the association between symbolic threat and political identity did vary by gender. Symbolic COVID-19 related threat perceptions were positively associated with a conservative identity for men but not women; for women, threat and political identity were unrelated.     

The processing of extraposed structures in English

In most languages, most of the syntactic dependency relations found in any given sentence are projective: the word-word dependencies in the sentence do not cross each other. Some syntactic dependency relations, however, are non-projective: some of their word-word dependencies cross each other. Non-projective dependencies are both rarer and more computationally complex than projective dependencies; hence, it is of natural interest to investigate whether there are any processing costs specific to non-projective dependencies, and whether factors known to influence processing of projective dependencies also affect non-projective dependency processing. We report three self-paced reading studies, together with corpus and sentence completion studies, investigating the comprehension difficulty associated with the non-projective dependencies created by the extraposition of relative clauses in English. We find that extraposition over either verbs or prepositional phrases creates comprehension difficulty, and that this difficulty is consistent with probabilistic syntactic expectations estimated from corpora. Furthermore, we find that manipulating the expectation that a given noun will have a postmodifying relative clause can modulate and even neutralize the difficulty associated with extraposition. Our experiments rule out accounts based purely on derivational complexity and/or dependency locality in terms of linear positioning. Our results demonstrate that comprehenders maintain probabilistic syntactic expectations that persist beyond projective-dependency structures, and suggest that it may be possible to explain observed patterns of comprehension difficulty associated with extraposition entirely through probabilistic expectations.     

Efficiency and interactions of alerting,orienting and executive networks: The impact of imperative stimulus type

The Attention Network Test (ANT) generates measures of three attention networks: alerting, orienting and executive control. Arrows have been generally used as imperative stimuli in the different versions of this paradigm. However, it is unknown whether the directional nature of these stimuli can modulate the efficiency of the executive control and its interaction with alerting and orienting. We developed three ANT variants to examine attentional effects in response to directional and non-directional stimuli. Arrows (ANTI-A), colored fruits (ANTI-F) and black geometrical-shape (ANTI-G) were used as imperative stimuli (i.e., flanker stimuli). Data collected from fifty-two university students, in two experiments, showed that arrows stimuli produced a greater interference effect and a greater orienting effect as compared to the other stimuli. Moreover, only arrows modulated the interaction between executive control and orienting: a reduced flanker effect in spatially cued trials was only observed in ANTI-A. These results suggest that the directional value of the stimuli increases the conflict and modulates the efficiency of executive control and its interaction with orienting network.