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.     

Maternal concepts and expectations regarding a preterm infant

The objective of the present study was: (a) to identify the concerns, verbally expressed, of 50 mothers regarding their preterm infants (PT) and then compare their verbal expression with those of 25 mothers of full-term infants (FT); and (b) to correlate the mothers' verbal expressions with maternal and infant variables. The following instruments were used to compose and characterize the sample: Structure Clinical Interview for DSM III-R Non-Patient (SCID/NP), State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and medical charts. Results showed that there was no difference between groups in term of mothers' expectations and conceptualizations; both groups exhibited predominantly positive expectations and concepts. In comparison with FT mothers, PT mothers verbally expressed more feelings and reactions predominantly negative or conflicting in relation to infant birth. Higher levels of maternal anxiety and depression in the PT Group were correlated with more verbal expressions about negative or conflicting emotions. In addition, lower birth weight, higher neonatal risk and longer length of stay in intensive care nursery of the infants were related with more negative or conflicting concepts by the mothers.     

Culture and the behavioural manifestations of traits: an application of the Act Frequency Approach

The behavioural manifestations of Big Five traits were compared across cultures using the Act Frequency Approach. American (n = 176) and Filipino (n = 195) students completed a Big Five measure and act frequency ratings for behaviours performed during the past month. Acts for specific traits cohered to an equivalent degree across cultures. In both cultures, the structure of act composites resembled the Big Five and the strength of trait‐behaviour relationships was very similar. Many acts were multidimensional and analyses revealed cultural commonalities and differences in the relevance and prevalence of acts for the Big Five traits. The results were more consistent with trait than cultural psychology perspectives, because traits predicted behaviour equally well, on average, in the two cultures. Copyright © 2007 John Wiley & Sons, Ltd.     

Fitting objects into holes: on the development of spatial cognition skills

The authors examined 14- to 26-month-old infants' understanding of the spatial relationships between objects and apertures in an object manipulation task. The task was to insert objects with various cross-sections (circular, square, rectangular, ellipsoid, and triangular) into fitting apertures. A successful solution required the infant to mentally rotate the object to be fit into the aperture and use that information to plan the action. The object was presented standing up in half of the trials; in the other half, it was lying down. The results showed that infants solved the problem consistently from age 22 months and that a successful solution was associated with appropriate preadjustments before the hand arrived with the block to the aperture. No sex differences were found.     

Depressive Realism: Wiser or Quieter?

The Psychological Record - Depressive realism consists of the lower personal control over uncontrollable events perceived by depressed as compared to nondepressed individuals. In this article, we...     

Attachment representations in mothers of preterm infants

The aim of the study was to assess attachment representations in mothers of preterm infants using the Working Model of Child Interview (WMCI) at the 12 months of the infant's corrected age. In addition, the relation between WMCI representation categories and the Edinburgh Postnatal Depression Scale score at 6 months of the infant's corrected age was studied. There were 38 mothers of preterm infants (<1500 g or <32 gestational weeks) and 45 mothers of full-term infants. The results showed no differences between the study groups in the distribution of the three main representation categories (balanced, disengaged and distorted). However, there were qualitative differences in representations between the groups. Furthermore, maternal depression symptoms were associated with distorted representation category. We suggest that despite the qualitative differences in the mothers’ representations, mothers of preterm infants are as likely to form balanced attachments with their infants as mothers of full-term infants.     

Diagnosing students’ misconceptions in algebra: Results from an experimental pilot study

Computer-based diagnostic assessment systems hold potential to help teachers identify sources of poor performance and to connect teachers and students to learning activities designed to help advance students’ conceptual understandings. The present article presents findings from a study that examined how students’ performance in algebra and their overcoming of common algebraic misconceptions were affected by the use of a diagnostic assessment system that focused on important algebra concepts. This study used a four-group randomized cluster trial design in which teachers were assigned randomly to one of four groups: a “business as usual” control group, a partial intervention group that was provided with access to diagnostic tests results, a partial intervention group that was provided with access to the learning activities, and a full intervention group that was given access to the test results and learning activities. Data were collected from 905 students (6th–12th grade) nested within 44 teachers. We used hierarchical linear modeling techniques to compare the effects of full, partial, and no (control) intervention on students’ algebraic ability and misconceptions. The analyses indicate that full intervention had a net positive effect on ability and misconception measures.