LTP in hippocampal area CA1 is induced by burst stimulation over a broad frequency range centered around delta

Long-term potentiation (LTP) is typically studied using either continuous high-frequency stimulation or theta burst stimulation. Previous studies emphasized the physiological relevance of theta frequency; however, synchronized hippocampal activity occurs over a broader frequency range. We therefore tested burst stimulation at intervals from 100 msec to 20 sec (10 Hz to 0.05 Hz). LTP at Schaffer collateral–CA1 synapses was obtained at intervals from 100 msec to 5 sec, with maximal LTP at 350–500 msec (2–3 Hz, delta frequency). In addition, a short-duration potentiation was present over the entire range of burst intervals. We found that N-methyl-d-aspartic acid (NMDA) receptors were more important for LTP induction by burst stimulation, but L-type calcium channels were more important for LTP induction by continuous high-frequency stimulation. NMDA receptors were even more critical for short-duration potentiation than they were for LTP. We also compared repeated burst stimulation with a single primed burst. In contrast to results from repeated burst stimulation, primed burst potentiation was greater when a 200-msec interval (theta frequency) was used, and a 500-msec interval was ineffective. Whole-cell recordings of postsynaptic membrane potential during burst stimulation revealed two factors that may determine the interval dependence of LTP. First, excitatory postsynaptic potentials facilitated across bursts at 500-msec intervals but not 200-msec or 1-sec intervals. Second, synaptic inhibition was suppressed by burst stimulation at intervals between 200 msec and 1 sec. Our data show that CA1 synapses are more broadly tuned for potentiation than previously appreciated.Long-term potentiation (LTP) is used as a model for studying synaptic events during learning and memory (Bliss and Collingridge 1993; Morris 2003; Lynch 2004). At most synapses, LTP is triggered by postsynaptic Ca²⁺ influx through N-methyl-d-aspartic acid (NMDA) glutamate receptors (Collingridge et al. 1983; Harris et al. 1984; Herron et al. 1986) and, under some conditions, through L-type voltage-gated Ca²⁺ channels (Grover and Teyler 1990, 1994; Morgan and Teyler 1999). LTP was discovered in the dentate gyrus (Bliss and Lomo 1973) following several seconds of 10–100 Hz stimulation of the perforant path. Since then, many LTP studies have used similar long, high-frequency stimulation (HFS) protocols, most typically 100 Hz, 1 sec (Bliss and Collingridge 1993). Although effective, HFS does not resemble physiological patterns of activity (Albensi et al. 2007). Patterned stimulation resembling physiological activity, in particular theta burst stimulation, is also effective for LTP induction (Larson et al. 1986; Staubli and Lynch 1987; Capocchi et al. 1992; Nguyen and Kandel 1997). Theta burst stimulation consists of short bursts (4–5 stimuli at 100 Hz) repeated at 5 Hz, which lies within the hippocampal theta frequency range (4–12 Hz) (Bland 1986; Buzsáki 2002). Primed burst stimulation, another form of patterned stimulation, involves delivery of a priming stimulus followed by a single short burst (Larson and Lynch 1986; Rose and Dunwiddie 1986). The temporal requirements for primed burst LTP are quite precise (Diamond et al. 1988; Greenstein et al. 1988; Larson and Lynch 1989): Intervals less than 140 msec or greater than 200 msec are ineffective.The mechanisms underlying theta frequency-dependent LTP have been studied primarily using the primed burst protocol (Larson and Lynch 1986, 1988, 1989; Pacelli et al. 1989; Davies and Collingridge 1996). Activation of GABA_B autoreceptors during the priming stimulus suppresses GABA release during the following burst (Davies et al. 1990; Lambert and Wilson 1994; Olpe et al. 1994), allowing greater postsynaptic depolarization (Larson and Lynch 1986; Pacelli et al. 1989) and more effective NMDA receptor activation (Davies and Collingridge 1996). Consequently, temporal requirements for primed burst potentiation match the time course of GABA_B autoreceptor-mediated suppression of GABA release (Davies et al. 1990; Davies and Collingridge 1993; Mott et al. 1993).Besides theta, hippocampal activity is observed at other frequencies, notably sharp waves (0.01–5 Hz) (Buzsáki 1986, 1989; Suzuki and Smith 1987) and low-frequency oscillations (≤1 Hz) (Wolansky et al. 2006; Moroni et al. 2007). These lower frequencies dominate during slow wave sleep (Buzsáki 1986; Suzuki and Smith 1987; Wolansky et al. 2006; Moroni et al. 2007), and contribute to hippocampal memory processing (Buzsáki 1989; Pennartz et al. 2002). While synchronized population activity over frequencies from <1 Hz to 12 Hz is associated with hippocampal memory function, previous LTP studies have focused on theta. We therefore investigated burst stimulation at frequencies from 0.05 Hz to 10 Hz. We found that CA1 synapses potentiate to some degree over this entire range and that maximal potentiation occurs around delta frequency rather than theta.     

Prescriptive Analysis: Further Individualization of Hypothesis Testing in Brief Experimental Analysis of Reading Fluency

Brief experimental analyses (BEA) have been used to identify effective individualized interventions for improving reading fluency with school-age children. Interventions involving incentives, modeling, repeated reading, and error correction are most often tested in a BEA. However, these interventions are rarely modified according to individual student needs. The current study examined the effects of varied levels of modeling (passage, sentence, word) and varied contingencies (tracking and fluency) on fluency in non-treated high-word overlap passages and general outcome measure passages. BEA-identified interventions were effective for improving reading fluency on non-treated passages for both second grade students and the third grade student. Notably, the effects reversed when intervention was withdrawn with one of the second grade students. Results are discussed in terms of considerations in the application of BEA technology in the schools.     

Confidence to Foster Across Cultures: Caregiver Perspectives

It is important to understand how cultural values, beliefs and traditions of foster parents are related to placement success because a substantial proportion of children in care come from culturally diverse backgrounds. In the present study participants were asked about resources they saw as necessary to improve their confidence fostering children from culturally diverse backgrounds. Sixty-one foster parents from a central Canadian province participated in a telephone interview that included the question: “what would help you feel more confident about fostering children with different values, beliefs and traditions?” A total of 35 unique responses were obtained and grouped together by 13 foster parents. Multidimensional scaling and cluster analysis were used to analyze the grouping data. Foster parents described six themes: understanding different cultures, training, self awareness, agency support, open discussion and community services. There were several similarities and differences between the perspectives of foster parents interviewed and the literature. Implications for future research are discussed.     

The relationship between objective and perceived fit with academic major, adaptability, and major-related outcomes

This study examined the effects of fit with college major on major commitment, GPA, college satisfaction, and changing one’s major. We further examined how individual adaptability may moderate the importance of fit on these outcomes. College students (N = 198; 160 women and 38 men; mean age = 19.14 years) completed an interest inventory used to assess objective fit with major, and also indicated their perceived fit with major. Results revealed little correlation between perceived fit and objective fit, with differential relationships to these outcomes. Perceived fit showed stronger positive correlations with affective major commitment and academic self-efficacy than did objective fit. Regarding the moderating role of adaptability, individuals higher in adaptability reported higher institutional satisfaction when there was lower perceived fit. Adaptability also had a main effect on major-related outcomes above and beyond the effects of fit. Practical and theoretical implications of these results are discussed.     

Beta-adrenergic receptor activation during distinct patterns of stimulation critically modulates the PKA-dependence of LTP in the mouse hippocampus

Activation of β-adrenergic receptors (β-ARs) enhances hippocampal memory consolidation and long-term potentiation (LTP), a likely mechanism for memory storage. One signaling pathway linked to β-AR activation is the cAMP-PKA pathway. PKA is critical for the consolidation of hippocampal long-term memory and for the expression of some forms of long-lasting hippocampal LTP. How does β-AR activation affect the PKA-dependence, and persistence, of LTP elicited by distinct stimulation frequencies? Here, we use in vitro electrophysiology to show that patterns of stimulation determine the temporal phase of LTP affected by β-AR activation. In addition, only specific patterns of stimulation recruit PKA-dependent LTP following β-AR activation. Impairments of PKA-dependent LTP maintenance generated by pharmacologic or genetic deficiency of PKA activity are also abolished by concurrent activation of β-ARs. Taken together, our data show that, depending on patterns of synaptic stimulation, activation of β-ARs can gate the PKA-dependence and persistence of synaptic plasticity. We suggest that this may allow neuromodulatory receptors to fine-tune neural information processing to meet the demands imposed by numerous synaptic activity profiles. This is a form of “metaplasticity” that could control the efficacy of consolidation of hippocampal long-term memories.The hippocampus importantly contributes to memory function in the mammalian brain (Zola-Morgan et al. 1986; Eichenbaum et al. 1990; Otto and Eichenbaum 1992; Phillips and LeDoux 1992; Remondes and Schuman 2004). It has reciprocal connections with numerous cortical areas, including those responsible for high-level integration of spatial and contextual data from the external environment (Lavenex and Amaral 2000). As such, the hippocampus is well positioned to receive and survey a broad range of information and select behaviorally salient data for long-term storage. Activity-dependent enhancement of hippocampal synaptic strength can store information carried in patterns of afferent neural activity (Bliss and Collingridge 1993; Moser et al. 1998; Nathe and Frank 2003; Whitlock et al. 2006). Substantial evidence suggests that long-term potentiation (LTP) of synaptic strength plays important roles in the formation of long-term memory (LTM) (Doyere and Laroche 1992; Bourtchuladze et al. 1994; Abel and Lattal 2001; Genoux et al. 2002). As such, mechanistic studies of LTP have shed valuable light on how the mammalian brain stores new information.The hippocampus receives dense noradrenergic projections from the locus coeruleus, a brain structure that can influence many vital brain functions, including attention, sleep, arousal, mood regulation, learning, and memory (Berridge and Waterhouse 2003). Both α- and β-adrenergic receptor subtypes are present on hippocampal neurons (Morrison and Foote 1986; Berridge and Waterhouse 2003), and noradrenaline (NA) acts on hippocampal β-adrenergic receptors (β-ARs) to facilitate the retention and recall of memory (Izquierdo et al. 1998; Ji et al. 2003; Murchison et al. 2004). In humans, stimulation of the noradrenergic neuromodulatory system enhances memory for emotional stimuli, and inhibition of β-ARs prevents this memory enhancement (Cahill et al. 1994; van Stegeren et al. 1998; O’Carroll et al. 1999).Consistent with the notion that selective enhancement of LTM may occur following β-AR activation, stimulation of β-ARs can also facilitate the persistence of LTP. In areas CA3 and CA1, β-AR activation facilitates the induction of long-lasting LTP when paired with certain patterns of electrical stimulation (Huang and Kandel 1996; Gelinas and Nguyen 2005). However, the mechanisms by which different patterns of stimulation control synaptic responsiveness to β-AR activation are unclear.β-ARs couple to guanine-nucleotide-binding regulatory Gs proteins to stimulate adenylyl cyclase activity and increase intracellular cAMP (Seeds and Gilman 1971; Maguire et al. 1977). A main target of cAMP signaling is activation of cAMP-dependent protein kinase (PKA), a kinase that is required for some forms of long-lasting LTP and for consolidation of hippocampal LTM (Frey et al. 1993; Abel et al. 1997; Nguyen and Woo 2003). Interestingly, the PKA-dependence of hippocampal LTP displays plasticity: Specific temporal patterns of synaptic stimulation, such as repeated and temporally spaced 100-Hz stimulation, elicit LTP that requires PKA for its expression (Woo et al. 2003). Also, spatial “enrichment” can increase the PKA-dependence of LTP in mice, and this is correlated with improved hippocampal memory function (Duffy et al. 2001). However, it is unclear whether activation of β-ARs can critically gate the PKA-dependence of LTP. In this study, we examine the effects of β-AR activation on LTP generated by various patterns of afferent stimulation in area CA1 of the hippocampus, and we determine the role of PKA in these β-AR-modulated forms of LTP.     

Constrained action selection in children with developmental coordination disorder

The effect of advance ('precue') information on short aiming movements was explored in adults, high school children, and primary school children with and without developmental coordination disorder (n=10, 14, 16, 10, respectively). Reaction times in the DCD group were longer than in the other groups and were more influenced by the extent to which the precue constrained the possible action space. In contrast, reaction time did not alter as a function of precue condition in adults. Children with DCD showed greater inaccuracy of response (despite the increased RT). We suggest that the different precue effects reflect differences in the relative benefits of priming an action prior to definitive information about the movement goal. The benefits are an interacting function of the task and the skill level of the individual. Our experiment shows that children with DCD gain a benefit from advance preparation in simple aiming movements, highlighting their low skill levels. This result suggests that goal-directed RTs may have diagnostic potential within the clinic.     

A comparative study of adolescent risk assessment instruments: predictive and incremental validity

Promising new adolescent risk assessment tools are being incorporated into clinical practice but currently possess limited evidence of predictive validity regarding their individual and/or combined use in risk assessments. The current study compares three structured adolescent risk instruments, Youth Level of Service/Case Management Inventory (YLS/CMI), Structured Assessment of Violence Risk in Youth (SAVRY), and Psychopathy Checklist: Youth Version (PCL:YV), for both predictive and incremental validity with respect to general and violent recidivism. Receiver operating characteristic and hierarchical logistic regression analyses revealed that the risk tools predicted general and violent recidivism to varying degrees of accuracy, but the SAVRY offered the most in incremental validity. Clinical implications and future directions for youth risk assessment are discussed.     

Orangutans (Pongo abelii) and a gorilla (Gorilla gorilla gorilla) match features in familiar and unfamiliar individuals

Great apes can perceive images as representative of corresponding real-life objects. Coupled with the potential advantages of identifying specific members of one’s species and mounting evidence for individual recognition in other non-humans, it seems likely that great apes would have the ability to identify conspecifics in photographs. The ability of four orangutans and a gorilla to match images of individuals of their own and a closely related but unfamiliar species was examined here for the first time. First, the subjects matched photographs of familiar conspecifics taken at various time points in a delayed matching-to-sample procedure (Experiment 1). Second, they matched different photographs of unfamiliar individuals of a different species (Experiment 2) at above chance levels. These results suggest that the subjects matched photographs by matching physical features, not necessarily by recognizing the identity of the individuals depicted. However, they also quickly learned to select photographs of familiar individuals when these photographs were paired with photographs of unfamiliar individuals of their own species (Experiment 3), and three subjects showed transfer to novel images of familiar and unfamiliar individuals. Thus, the findings support the idea that subjects attended to physical features to identify individuals that they could categorize on the basis of familiarity.     

How you Perceive Time Matters for how you Feel in School: Investigating the Link Between Time Perspectives and Academic Emotions

Research on time perspectives and academic emotions have proceeded in parallel with little cross-fertilization of ideas. The aim of this study was to explore the synergies between these two lines of inquiry by looking at how time perspectives are related to different academic emotions. Filipino university students answered relevant questionnaires. Regression analyses were conducted to examine how time perspectives predicted different academic emotions. Results indicated that future time perspective was positively associated with positive academic emotions such as enjoyment, hope, and pride. Present-fatalistic time perspective was positively associated with negative academic emotions such as anger, anxiety, shame, hopelessness, and boredom. Theoretical and practical implications are discussed.     

New Directions in the Cognitive-Behavioral Treatment of OCD: Theory,Research, and Practice

The beneficial effects of cognitive-behavioral interventions (particularly exposure and response prevention) for OCD are among the most consistent research findings in the mental health literature. Nevertheless, even after an adequate trial, many individuals experience residual symptoms, and others never receive adequate treatment due to limited access. These and other issues have prompted clinicians and researchers to search for ways to improve the conceptual and practical aspects of existing treatment approaches, as well as look for augmentation strategies. In the present article, we review a number of recent developments and new directions in the psychological treatment of OCD, including (a) the application of inhibitory learning approaches to exposure therapy, (b) the development of acceptance-based approaches, (c) involvement of caregivers (partners and parents) in treatment, (d) pharmacological cognitive enhancement of exposure therapy, and (e) the use of technology to disseminate effective treatment. We focus on both the conceptual/scientific and practical aspects of these topics so that clinicians and researchers alike can assess their relative merits and disadvantages.