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

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

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

Infant pain vs. pain with parental suppression: Immediate and enduring impact on brain, pain and affect.

BackgroundIn the short term, parental presence while a human infant is in pain buffers the immediate pain responses, although emerging evidence suggests repeated social buffering of pain may have untoward long-term effects.Methods/findingTo explore the short- and long-term impacts of social buffering of pain, we first measured the infant rat pup's [postnatal day (PN) 8, or 12] response to mild tail shock with the mother present compared to shock alone or no shock. Shock with the mother reduced pain-related behavioral activation and USVs of pups at both ages and reduced Fos expression in the periaqueductal gray, hypothalamic paraventricular nucleus, and the amygdala at PN12 only. At PN12, shock with the mother compared to shock alone differentially regulated expression of several hundred genes related to G-protein-coupled receptors (GPCRs) and neural development, whereas PN8 pups showed a less robust and less coherent expression pattern. In a second set of experiments, pups were exposed to daily repeated Shock-mother pairings (or controls) at PN5-9 or PN10-14 (during and after pain sensitive period, respectively) and long-term outcome assessed in adults. Shock+mother pairing at PN5-9 reduced adult carrageenan-induced thermal hyperalgesia and reduced Fos expression, but PN10-14 pairings had minimal impact. The effect of infant treatment on adult affective behavior showed a complex treatment by age dependent effect. Adult social behavior was decreased following Shock+mother pairings at both PN5-9 and PN10-14, whereas shock alone had no effect. Adult fear responses to a predator odor were decreased only by PN10-14 treatment and the infant Shock alone and Shock+mother did not differ.Conclusions/significanceOverall, integrating these results into our understanding of long-term programming by repeated infant pain experiences, the data suggest that pain experienced within a social context impacts infant neurobehavioral responses and initiates an altered developmental trajectory of pain and affect processing that diverges from experiencing pain alone