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

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