Developmental transitions in amygdala PKC isoforms and AMPA receptor expression associated with threat memory in infant rats

Although infants learn and remember, they rapidly forget, a phenomenon known as infantile amnesia. While myriad mechanisms impact this rapid forgetting, the molecular events supporting memory maintenance have yet to be explored. To explore memory mechanisms across development, we used amygdala-dependent odor-shock conditioning and focused on mechanisms important in adult memory, the AMPA receptor subunits GluA1/2 and upstream protein kinases important for trafficking AMPAR, protein kinase M zeta (PKMζ) and iota/lambda (PKCι/λ). We use odor-shock conditioning in infant rats because it is late-developing (postnatal day, PN10) and can be modulated by corticosterone during a sensitive period in early life. Our results show that memory-related molecules did not change in pups too young to learn threat (PN8) but were activated in pups old enough to learn (PN12), with increased PKMζ-PKCι/λ and GluA2 similar to that observed in adult memory, but with an uncharacteristic decrease in GluA1. This molecular signature and behavioral avoidance of the conditioned odor was recapitulated in PN8 pups injected with CORT before conditioning to precociously induce learning. Blocking learning via CORT inhibition in older pups (PN12) blocked the expression of these molecules. PN16 pups showed a more adult-like molecular cascade of increased PKMζ-PKCι/λ and GluA1–2. Finally, at all ages, zeta inhibitory peptide (ZIP) infusions into the amygdala 24 hr after conditioning blocked memory. Together, these results identify unique features of memory processes across early development: AMPAR subunits GluA1/2 and PKC isoform expression are differentially used, which may contribute to mechanisms of early life forgetting

Gas phase production of NHD2 in L134N

We show analytically that large abundances of NH2D and NHD2 can be produced by gas phase chemistry in the interiors of cold dense clouds. The calculated fractionation ratios are in good agreement with the values that have been previously determined in L134N and suggest that triply-deuterated ammonia could be detectable in dark clouds. Grain surface reactions may lead to similar NH2D and NHD2 enhancements but, we argue, are unlikely to contribute to the deuteration observed in L134N.Comment: 6 pages, 2 figures, uses psfig.sty and emulateapj.sty, to appear in Astrophysical Journal, vol 55

Analysis and packaging of radiochemical solar neutrino data. 1. Bayesian approach

According to current practice, the results of each run of a radiochemical solar neutrino experiment comprise an estimate of the flux and upper and lower error estimates. These estimates are derived by a maximum-likelihood procedure from the times of decay events in the analysis chamber. This procedure has the following shortcomings: (a) Published results sometimes include negative flux estimates. (b) Even if the flux estimate is non-negative, the probability distribution function implied by the flux and error estimates will extend into negative territory; and (c) The overall flux estimate derived from the results of a sequence of runs may differ substantially from an estimate made by a global analysis of all of the timing data taken together. These defects indicate that the usual packaging of data in radiochemical solar neutrino experiments provides an inadequate summary of the data, which implies a loss of information. This article reviews this problem from a Bayesian perspective, and suggests an alternative scheme for the packaging of radiochemical solar neutrino data, which is we believe free from the above objections.Comment: 8 page

A Search for O VI in the Winds of B-Type Stars

We have conducted a survey of FUSE spectra of 235 Galactic B-type stars in order to determine the boundaries in the H-R diagram for the production of the superion O VI in their winds. By comparing the locations and morphology of otherwise unidentified absorption features in the vicinity of the O VI resonance doublet with the bona fide wind profiles seen in archival IUE spectra of the resonance lines of N V, Si IV and C IV, we were able to detect blueshifted O VI lines in the spectra of giant and supergiant stars with temperature classes as late as B1. No features attributable to O VI were detected in dwarfs later than B0, or in stars of any luminosity class later than B1, although our ability to recognize weak absorption features in these stars is severely restricted by blending with photospheric and interstellar features. We discuss evidence that the ratio of the ion fractions of O VI and N V is substantially different in the winds of early B-type stars than O-type stars.Comment: Accepted for publication in the A&

The Neurogenesis Actuator and NR2B/NMDA Receptor Antagonist Ro25-6981 Consistently Improves Spatial Memory Retraining Via Brain Region-Specific Gene Expression

NR2B-containing NMDA (NR2B/NMDA) receptors are important in controlling neurogenesis and are involved in generating spatial memory. Ro25-6981 is a selective antagonist at these receptors and actuates neurogenesis and spatial memory. Inter-structural neuroanatomical profiles of gene expression regulating adult neurogenesis and neuroapoptosis require examination in the context of memory retrieval and reversal learning. The aim was to investigate spatial memory retrieval and reversal learning in relation to gene expression-linked neurogenetic processes following blockade of NR2B/NMDA receptors by Ro25-6981. Rats were trained in Morris water maze (MWM) platform location for 5 days. Ro25-6981 was administered (protocol days 6–7) followed by retraining (days 15–18 or 29–32). Platform location was tested (on days 19 or 33) then post-mortem brain tissue sampling (on days 20 or 34). The expression of three genes known to regulate cell proliferation (S100a6), differentiation (Ascl1), and apoptosis (Casp-3) were concomitantly evaluated in the hippocampus, prefrontal cortex, and cerebellum in relation to the MWM performance protocol. Following initial training, Ro25-6981 enhanced visuospatial memory retrieval performance during further retraining (protocol days 29–32) but did not influence visuospatial reversal learning (day 33). Hippocampal Ascl1 and Casp-3 expressions were correspondingly increased and decreased while cerebellar S100a6 and Casp-3 activities were decreased and increased respectively 27 days after Ro25-6981 treatment. Chronological analysis indicated a possible involvement of new mature neurons in the reconfiguration of memory processes. This was attended by behavioral/gene correlations which revealed direct links between spatial memory retrieval enhancement and modified gene activity induced by NR2B/NMDA receptor blockade and upregulation

Enriched Environment Increases PCNA and PARP1 Levels in Octopus vulgaris Central Nervous System: First Evidence of Adult Neurogenesis in Lophotrochozoa

Organisms showing a complex and centralized nervous system, such as teleosts, amphibians, reptiles, birds and mammals, and among invertebrates, crustaceans and insects, can adjust their behavior according to the environmental challenges. Proliferation, differentiation, migration, and axonal and dendritic development of newborn neurons take place in brain areas where structural plasticity, involved in learning, memory, and sensory stimuli integration, occurs. Octopus vulgaris has a complex and centralized nervous system, located between the eyes, with a hierarchical organization. It is considered the most "intelligent" invertebrate for its advanced cognitive capabilities, as learning and memory, and its sophisticated behaviors. The experimental data obtained by immunohistochemistry and western blot assay using proliferating cell nuclear antigen and poli (ADP-ribose) polymerase 1 as marker of cell proliferation and synaptogenesis, respectively, revealed cell proliferation in areas of brain involved in learning, memory, and sensory stimuli integration. Furthermore, we showed how enriched environmental conditions affect adult neurogenesis

Social instability, hippocampal plasticity and resilience

Experience-dependent changes in the production and function of new neurons may serve as a means to fine-tune the hippocampus to the predicted environment. Here we describe a series of studies done to examine the effects of naturalistic social disruption on structural plasticity and behavior in adult rats. Our results provide novel mechanistic evidence that social disruption shapes behavior in an adaptive way by reducing adult neurogenesis in the hippocampus. First, we developed an ethologically relevant model of social instability by forming stable dominance hierarchies in a visible burrow system and then switching dominant rats between hierarchies, a manipulation that increased aggression. Next, we examined the brains of rats subjected to social disruption and compared them to those living in a stable hierarchy and to those living in standard laboratory cages. We found that social disruption dramatically reduced the number of neural stem cells, as well as the number of new neurons, in the hippocampus regardless of social position. Instead of producing the predicted deleterious consequences of social stress, like impaired cognition and increased anxiety, we found no change in cognition and reduced anxiety-like behavior in rats from a disrupted hierarchy. We also found that socially disrupted rats did not show impairments in the ability to detect novelty in a social setting, but they did show a preference for familiar, as opposed to novel, conspecifics. Taken together, this behavioral profile suggests a potential ¿stress inoculation¿ or resilience, as opposed to the emergence of pathology. Next, we used two approaches to investigate whether these behavioral effects were causally linked to the reduction in adult neurogenesis in the hippocampus. We used oxytocin to stimulate adult neurogenesis just after social disruption occurred and found that this manipulation prevented the preference for familiar conspecifics. Then we used transgenic conditional neurogenesis knockout (GFAP-TK) rats to reduce adult neurogenesis in rats without social disruption experience and found that these rats preferred familiar rats, similar to what we observed in social disrupted wild-types. The mechanisms by which new neurons influence social preference remain to be determined

Unique infant neurobiology produces distinctive trauma processing

Trauma experienced in early life has unique neurobehavioral outcomes related to later life psychiatric sequelae. Recent evidence has further highlighted the context of infant trauma as critical, with trauma experienced within species-atypical aberrations in caregiving quality as particularly detrimental. Using data from primarily rodent models, we review the literature on the interaction between trauma and attachment in early life, which highlights the role of the caregiver’s presence in engagement of attachment brain circuitry and suppressing threat processing by the amygdala. Together these data suggest that infant trauma processing and its enduring effects are impacted by both the immaturity of brain areas for processing trauma and the unique functioning of the early-life brain, which is biased towards forming robust attachments regardless of the quality of care. Understanding the critical role of the caregiver in further altering early life brain processing of trauma is important for developing age-relevant treatment and interventions. Keywords: Trauma, Attachment, Amygdala, Development, Stress, Sensitive perio

Unique neurobiology during the sensitive period for attachment produces distinctive infant trauma processing

Background: Trauma has neurobehavioral effects when experienced at any stage of development, but trauma experienced in early life has unique neurobehavioral outcomes related to later life psychiatric sequelae. Recent evidence has further highlighted the context of infant trauma as a critical variable in determining its immediate and enduring consequences. Trauma experienced from an attachment figure, such as occurs in cases of caregiver child maltreatment, is particularly detrimental. Methods: Using data primarily from rodent models, we review the literature on the interaction between trauma and attachment in early life, which highlights the role of the caregiver's presence in engagement of attachment brain circuitry and suppressing threat processing by the amygdala. We then consider how trauma with and without the caregiver produces long-term changes in emotionality and behavior, and suggest that these experiences initiate distinct pathways to pathology. Results: Together these data suggest that infant trauma processing and its enduring effects are impacted by both the immaturity of brain areas for processing trauma and the unique functioning of the early-life brain, which is biased toward processing information within the attachment circuitry. Conclusion: An understanding of developmental differences in trauma processing as well as the critical role of the caregiver in further altering early life brain processing of trauma is important for developing age-relevant treatment and interventions

Early life adversity during the infant sensitive period for attachment: Programming of behavioral neurobiology of threat processing and social behavior

Animals, including humans, require a highly coordinated and flexible system of social behavior and threat evaluation. However, trauma can disrupt this system, with the amygdala implicated as a mediator of these impairments in behavior. Recent evidence has further highlighted the context of infant trauma as a critical variable in determining its immediate and enduring consequences, with trauma experienced from an attachment figure, such as occurs in cases of caregiver-child maltreatment, as particularly detrimental. This review focuses on the unique role of caregiver presence during early-life trauma in programming deficits in social behavior and threat processing. Using data primarily from rodent models, we describe the interaction between trauma and attachment during a sensitive period in early life, which highlights the role of the caregiver’s presence in engagement of attachment brain circuitry and suppressing threat processing by the amygdala. These data suggest that trauma experienced directly from an abusive caregiver and trauma experienced in the presence of caregiver cues produce similar neurobehavioral deficits, which are unique from those resulting from trauma alone. We go on to integrate this information into social experience throughout the lifespan, including consequences for complex scenarios, such as dominance hierarchy formation and maintenance