Epigenetic Alterations Are Critical for Fear Memory Consolidation and Synaptic Plasticity in the Lateral Amygdala

Epigenetic mechanisms, including histone acetylation and DNA methylation, have been widely implicated in hippocampal-dependent learning paradigms. Here, we have examined the role of epigenetic alterations in amygdala-dependent auditory Pavlovian fear conditioning and associated synaptic plasticity in the lateral nucleus of the amygdala (LA) in the rat. Using Western blotting, we first show that auditory fear conditioning is associated with an increase in histone H3 acetylation and DNMT3A expression in the LA, and that training-related alterations in histone acetylation and DNMT3A expression in the LA are downstream of ERK/MAPK signaling. Next, we show that intra-LA infusion of the histone deacetylase (HDAC) inhibitor TSA increases H3 acetylation and enhances fear memory consolidation; that is, long-term memory (LTM) is enhanced, while short-term memory (STM) is unaffected. Conversely, intra-LA infusion of the DNA methyltransferase (DNMT) inhibitor 5-AZA impairs fear memory consolidation. Further, intra-LA infusion of 5-AZA was observed to impair training-related increases in H3 acetylation, and pre-treatment with TSA was observed to rescue the memory consolidation deficit induced by 5-AZA. In our final series of experiments, we show that bath application of either 5-AZA or TSA to amygdala slices results in significant impairment or enhancement, respectively, of long-term potentiation (LTP) at both thalamic and cortical inputs to the LA. Further, the deficit in LTP following treatment with 5-AZA was observed to be rescued at both inputs by co-application of TSA. Collectively, these findings provide strong support that histone acetylation and DNA methylation work in concert to regulate memory consolidation of auditory fear conditioning and associated synaptic plasticity in the LA

Recall and Reconsolidation of Contextual Fear Memory: Differential Control by ERK and Zif268 Expression Dosage

Compelling evidence points to the existence of independent cellular processes involved in the consolidation and reconsolidation of memory. For instance, a double dissociation has been reported between hippocampal Extracellular-Regulated Kinase-1/2 (ERK1/2) activity being necessary for contextual fear conditioning (CFC) consolidation but not reconsolidation. Conversely, hippocampal expression of the immediate early gene Zif268 is necessary for CFC reconsolidation but not consolidation. Since we previously reported that ERK1/2 controls the transcription of Zif268 in the hippocampus, we examined the precise role of ERK1/2 activity and Zif268 gene expression dosage in CFC memory processing. For this, we first assessed performance of Zif268 homozygous and heterozygous mutant mice in a CFC paradigm. Whereas Zif268−/− mice displayed a deficit of both consolidation and reconsolidation, Zif268+/− mice displayed a selective deficit of reconsolidation only, therefore pointing to the relationship between Zif268 gene expression dosage and CFC memory processing. Zif268 gene expression dosage interfered with the reconsolidation process if and only if CFC memory was relatively recently encoded and directly reactivated. Furthermore, CFC memory strengthening previously reported to involve Zif268 expression in the hippocampus was spared in Zif268+/− mice. Finally, blocking ERK1/2 activity prior to CFC retrieval prevented the deficit of reconsolidation observed in Zif268+/− mice. Collectively, these results highlight a tight relationship between Zif268 gene expression dosage and CFC memory processing. They also suggest that ERK1/2 activity upon CFC memory recall is necessary for its retrieval, a prerequisite for its reactivation and subsequent reconsolidation

Kinematic pelvic tilt during gait alters functional cup position in total hip arthroplasty

Static pelvic tilt impacts functional cup position in total hip arthroplasty (THA). In the current study we investigated the effect of kinematic pelvic changes on cup position. In the course of a prospective controlled trial postoperative 3D-computed tomography (CT) and gait analysis before and 6 and 12 months after THA were obtained in 60 patients. Kinematic pelvic motion during gait was measured using Anybody Modeling System. By fusion with 3D-CT, the impact of kinematic pelvic tilt alterations on cup anteversion and inclination was calculated. Furthermore, risk factors correlating with high pelvic mobility were evaluated. During gait a high pelvic range of motion up to 15.6° exceeding 5° in 61.7% (37/60) of patients before THA was found. After surgery, the pelvis tilted posteriorly by a mean of 4.0 ± 6.6° (p < .001). The pelvic anteflexion led to a mean decrease of −1.9 ± 2.2° (p < .001) for cup inclination and −15.1 ± 6.1° (p < .001) for anteversion in relation to the anterior pelvic plane (APP). Kinematic pelvic changes resulted in a further change up to 2.3° for inclination and up to 12.3° for anteversion. In relation to the preoperative situation differences in postoperative cup position ranged from −4.4 to 4.6° for inclination and from −7.8 to 17.9° for anteversion, respectively. Female sex (p < .001) and normal body weight (p < .001) correlated with high alterations in pelvic tilt. Kinematic pelvic changes highly impact cup anteversion in THA. Surgeons using the APP as reference should aim for a higher anteversion of about 15° due to the functional anteflexion of the pelvis during gait

Titanosaur Osteoderms from the Upper Cretaceous of Lo Hueco (Spain) and Their Implications on the Armor of Laurasian Titanosaurs

Titanosaurs are the only sauropod dinosaurs known to bear a dermal armor. Their osteoderms are relatively rare finds, with few more than a hundred specimens recovered worldwide. Also, little is known about their intra-individual, intra-specific or inter-specific variability. The macrovertebrate site of Lo Hueco (Upper Cretaceous; Cuenca, Spain) has yielded several complete specimens of osteoderms, some associated with fairly articulated specimens. They are all variations of the morphotype known as bulb and root. The presence of only this morphotype in Europe, which is considered as the primitive condition among titanosaurs, seems to indicate that the known Upper Cretaceous Laurasian titanosaurs only bore these referred bulb and root osteoderms. An eliptic Fourier analysis on the outline of complete specimens from this morphotype reveals: i) that they truly are part of a morphological cline; and ii) the existence of a consistent correlation between the outline and the morphology of the bulb. Such variation along a cline is more consistent with intra-individual rather than inter-specific variation. The osteoderms associated with a single titanosaur individual from Lo Hueco reinforce this hypothesis