Behavioral alterations in mice lacking the translation repressor 4E-BP2

The requirement for de novo protein synthesis during multiple forms of learning, memory and behavior is well-established; however, we are only beginning to uncover the regulatory mechanisms that govern this process. In order to determine how translation initiation is regulated during neuroplasticity we engineered mutant C57Bl/6J mice that lack the translation repressor eukaryotic initiation factor 4E-binding protein 2 (4E-BP2) and have previously demonstrated that 4E-BP2 plays a critical role in hippocampus-dependent synaptic plasticity and memory. Herein, we examined the 4E-BP2 knockout mice in a battery of paradigms to address motor activity and motor skill learning, anxiety and social dominance behaviors, working memory and conditioned taste aversion. We found that the 4E-BP2 knockout mice demonstrated altered activity in the rotating rod test, light/dark exploration test, spontaneous alternation T-maze and conditioned taste aversion test. The information gained from these studies builds a solid foundation for future studies on the specific role of 4E-BP2 in various types of behavior, and for a broader, more detailed examination of the mechanisms of translational control in the brain.     

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.     

MAPK activation in the hippocampus in vivo is correlated with experimental setting

The mitogen-activated protein kinase (MAPK) pathway is an evolutionarily conserved signaling cascade involved in both synaptic plasticity and memory formation. Following our recent observation of translation regulation in taste learning and memory, we aimed to study MAPK-dependent translation regulation in long-term potentiation (LTP), a cellular model of learning and memory. We first analyzed ERK1/2 activation following high-frequency stimulation in the dentate gyrus (DG) of the hippocampus, in vivo. Surprisingly, our results indicate that the activation of both ERK2 and p38 was strongly affected by the order in which the DG was dissected out, but not by other experimental parameters. Specifically, we found that ERK2 and p38 phosphorylation were higher in the second than in the first dentate gyrus removed (up to 30s apart). Similar results were obtained when we isolated the 'order of removal' factor by looking at MAPK phosphorylation in rats that had not undergone any electrophysiological procedure (i.e., na?ve rats). This effect is so robust, that it probably masks the effect of LTP induction on MAPK activation. We suggest that some of the correlations found between MAPK activation and brain function in vivo may be due to cellular stress. In addition, careful experimental procedures and control are indispensable in the analysis of biochemical correlations of post-translation modifications that subserve both general neuronal function and synaptic plasticity.     

Acquisition and extinction in autoshaping

C. R. Gallistel and J. Gibbon (2000) presented quantitative data on the speed with which animals acquire behavioral responses during autoshaping, together with a statistical model of learning intended to account for them. Although this model captures the form of the dependencies among critical variables, its detailed predictions are substantially at variance with the data. In the present article, further key data on the speed of acquisition are used to motivate an alternative model of learning, in which animals can be interpreted as paying different amounts of attention to stimuli according to estimates of their differential reliabilities as predictors.     

Trauma is not the whole story: Trajectories of responses to childhood disasters intertwining with Life following the Indian Ocean tsunami

In an era of global threats, understanding the implications of disasters on young people's life course is of central importance. A particular emphasis should be placed on non-Western economically developing societies that are considered as vulnerable and are less studied, and on social groups within these societies that are underrepresented. The present study focuses on young Sri Lankan women who experienced the 2004 Indian Ocean tsunami as children. Thirteen young women generated their life stories in semi-structured interviews, 12 years after the disaster had elapsed. Holistic narrative analysis revealed new variations and in-depth meanings in disaster response trajectories and presented the intertwining courses of the responses to the Potentially Traumatic Event (PTE) with ecological aspects throughout development, as in Trajectories intertwining with Life (TiL). This study provides empirical, methodological, conceptual and practical innovations to the study of human development throughout the life course, within the interdisciplinary fields of trauma and disasters.

Highlights

• This research is interested in how childhood disaster response trajectories among an understudied population are understood through an ecological-developmental perspective.
• Life stories uncover Trajectories intertwining with Life (TiL) among Sri Lankan women who were children during the Indian Ocean tsunami.
• The TiL unique outcomes, integrating trauma responses as inseparable from ecological and developmental aspects, offer various theoretical and applied implications.