Connectivity between the central nucleus of the amygdala and the bed nucleus of the stria terminalis in the non-human primate: neuronal tract tracing and developmental neuroimaging studies.

The lateral division of the bed nucleus of the stria terminalis (BSTL) and central nucleus of the amygdala (Ce) form the two poles of the 'central extended amygdala', a theorized subcortical macrostructure important in threat-related processing. Our previous work in nonhuman primates, and humans, demonstrating strong resting fMRI connectivity between the Ce and BSTL regions, provides evidence for the integrated activity of these structures. To further understand the anatomical substrates that underlie this coordinated function, and to investigate the integrity of the central extended amygdala early in life, we examined the intrinsic connectivity between the Ce and BSTL in non-human primates using ex vivo neuronal tract tracing, and in vivo diffusion-weighted imaging and resting fMRI techniques. The tracing studies revealed that BSTL receives strong input from Ce; however, the reciprocal pathway is less robust, implying that the primate Ce is a major modulator of BSTL function. The sublenticular extended amygdala (SLEAc) is strongly and reciprocally connected to both Ce and BSTL, potentially allowing the SLEAc to modulate information flow between the two structures. Longitudinal early-life structural imaging in a separate cohort of monkeys revealed that extended amygdala white matter pathways are in place as early as 3 weeks of age. Interestingly, resting functional connectivity between Ce and BSTL regions increases in coherence from 3 to 7 weeks of age. Taken together, these findings demonstrate a time period during which information flow between Ce and BSTL undergoes postnatal developmental changes likely via direct Ce â†’ BSTL and/or Ce â†” SLEAc â†” BSTL projections.

Fibroblast growth factor 2 alters the oxytocin receptor in a developmental model of anxiety-like behavior in male rat pups.

We aimed to determine the short-term effects of early-life stress in the form of maternal separation (MS) on anxiety-like behavior in male rat pups. In order to assess anxiety, we measured 40kHz separation-induced ultrasonic vocalizations (USV) on postnatal day (PND) 11. We further aimed to evaluate the potential involvement of two neurochemical systems known to regulate social and anxiety-like behaviors throughout life: oxytocin (OT) and fibroblast growth factor 2 (FGF2). For these purposes, we tested the effects of neonatal administration (on PND1) of an acute dose of FGF2 on USV and its potential interaction with MS. In addition, we validated the anxiolytic effects of OT and measured oxytocin receptor (OTR) gene expression, binding and epigenetic regulation via histone acetylation. Our results show that MS potentiated USV while acute administration of OT and FGF2 attenuated them. Further, we found that both FGF2 and MS increased OTR gene expression and the association of acH3K14 with the OTR promoter in the bed nucleus of the stria terminalis (BNST). Comparable changes, though not as pronounced, were also found for the central amygdala (CeA). Our findings suggest that FGF2 may exert its anxiolytic effects in male MS rats by a compensatory increase in the acetylation of the OTR promoter to overcome reduced OT levels in the BNST.

[Paleoamygdala: the morphogenesis of nuclear-type, paleocortical and intermediate formations in the perial of postnatal development in rats].

The cytoarchitectonics and expression of apoptosis (as an indicator of stabilization of formative processes) in nuclear, paleocortical, and intermediate formations of the paleoamygdala of the rat ondays 21, 24, 28, and 31 of postnatal development was studied. The results of analysis suggest that the morphogenesis of these formations is characterized by heterochrony due to the complexity of their structural organization predefined by the phylogenetic age. On day 21 of postnatal development of the rat, only the dorsomedial nucleus is well differentiated; on days 24-28, the posterior medial nucleus is well differentiated. The medial part of the posterior cortical nucleus (intermediate formation) is differentiated from the lateral part of this nucleus on day 28. The lateral part of the posterior cortical nucleus, which exhibits the characteristics of a paleocortical formation, acquires the cytoarchitectonics characteristic of an adult animal on day 31 of postnatal development. The dynamics of changes in the apoptotic index reflects the stabilization of morphogenetic processes characterized on the basis of cytoarchitectonic criteria. The results of this study and the neurogenetic data, indicating the presence of spatiotemporal gradients in the formation of the amygdaloid complex and the multiplicity of the original histogenetic domains, confirm the correctness of the previous concept (Akmaev and Kalimullina, 1993) on the substrate of this brain structure as a nuclear-paleocortical component of the brain.

Effect of age on methylphenidate-induced conditioned taste avoidance and related BDNF/TrkB signaling in the insular cortex of the rat.

RATIONALE: Drug use and abuse is thought to be a function of the balance between its rewarding and aversive effects, such that the rewarding effects increase the likelihood of use while the drug's dissociable aversive effects limit it. Adolescents exhibit a shift in this balance toward reward, which may ultimately lead to increased use. Importantly, recent work shows that adolescents are also protected from the aversive effects of many abusable drugs as measured by conditioned taste avoidance (CTA). However, such effects of methylphenidate (MPH, widely prescribed to adolescents with ADHD) have not been characterized. OBJECTIVES: The effect of age on MPH-induced CTA was assessed. In addition, MPH-induced changes in brain-derived neurotrophic factor (BDNF) activity in the insular cortex (IC) and central nucleus of the amygdala (CeA), known to be important to CTA, were examined and related to CTAs in adolescents and adults. METHODS: CTAs induced by MPH (0, 10, 18, and 32 mg/kg) were assessed in adolescent (n = 34) and adult (n = 33) male Sprague Dawley rats. Following MPH CTA, IC and CeA tissue was probed for differences in BDNF and tropomyosin-related kinase receptor-B (TrkB) using Western blots. RESULTS: Blunted expression of MPH CTA was observed in the adolescents versus adults, which correlated with generally attenuated adolescent BDNF/TrkB activity in the IC, but the drug effects ran contrary to the expression of CTA. CONCLUSIONS: Adolescents are protected from the aversive effects of MPH versus adults, but further work is needed to characterize the possible involvement of BDNF/TrkB.