A Basomedial Amygdala to Intercalated Cells Microcircuit Expressing PACAP and Its Receptor PAC1 Regulates Contextual Fear

Trauma can cause dysfunctional fear regulation leading some people to develop disorders, such as post-traumatic stress disorder (PTSD). The amygdala regulates fear, whereas PACAP (pituitary adenylate activating peptide) and PAC1 receptors are linked to PTSD symptom severity at genetic/epigenetic levels, with a strong link in females with PTSD. We discovered a PACAPergic projection from the basomedial amygdala (BMA) to the medial intercalated cells (mICCs) in adult mice. In vivo optogenetic stimulation of this pathway increased CFOS expression in mICCs, decreased fear recall, and increased fear extinction. Selective deletion of PAC1 receptors from the mICCs in females reduced fear acquisition, but enhanced fear generalization and reduced fear extinction in males. Optogenetic stimulation of the BMA-mICC PACAPergic pathway produced EPSCs in mICC neurons, which were enhanced by the PAC1 receptor antagonist, PACAP 6-38. Our findings show that mICCs modulate contextual fear in a dynamic and sex-dependent manner via a microcircuit containing the BMA and mICCs, and in a manner that was dependent on behavioral state.SIGNIFICANCE STATEMENT Traumatic stress can affect different aspects of fear behaviors, including fear learning, generalization of learned fear to novel contexts, how the fear of the original context is recalled, and how fear is reduced over time. While the amygdala has been studied for its role in regulation of different aspects of fear, the molecular circuitry of this structure is quite complex. In addition, aspects of fear can be modulated differently in males and females. Our findings show that a specific circuitry containing the neuropeptide PACAP and its receptor, PAC1, regulates various aspects of fear, including acquisition, generalization, recall, and extinction in a sexually dimorphic manner, characterizing a novel pathway that modulates traumatic fear.     

Progression of sleep disturbances in Parkinson’s disease: a 5-year longitudinal study

Journal of Neurology - Sleep disorders can occur in early Parkinson’s disease (PD). However, the relationship between different sleep disturbances and their longitudinal evolution has not...     

Magnitude and time course of changes in maximal oxygen uptake in response to distinct regimens of chronic interval training in sedentary women

Purpose

This study aimed to compare changes in maximal oxygen uptake (VO_2max) in response to two regimens of chronic interval training.

Methods

Twenty healthy sedentary women (mean ± SD age and VO_2max = 23.0 ± 5.7 years and 30.1 ± 4.4 mL kg^?1 min^?1, respectively) were randomized to complete 12 weeks of one of two interval training regimes, while an additional seven women served as controls. Training was performed 3 days week^?1 on a cycle ergometer and consisted of 6–10 bouts of 1 min duration at lower (60–80 % W _max = LO, n = 10) or more intense (80–90 % W _max = HI, n = 10) workloads separated by a brief recovery. Every 3 weeks, measures of VO_2max and W _max were repeated to assign new training intensities. Changes in blood pressure and body composition were also examined.

Results

Data revealed significant (p < 0.001) improvements in VO_2max in LO (22.3 ± 6.9 %) and HI (21.9 ± 11.6 %) that were similar (p > 0.05) between groups. Approximately 60 % of the increase in VO_2max in HI was observed in the initial 3 weeks, compared to only 20 % in LO. No change (p > 0.05) in body weight or body composition was revealed in response to training. Results demonstrate that a relatively prolonged regimen of moderate or more intense interval training induces similar improvements in cardiorespiratory fitness, although HI induced greater increases in VO_2max early on in training than LO. Completion of more intense interval training may be an effective means to expedite increases in VO₂max soon after initiation of exercise training.     

Pregnancy-Associated Cardiac Hypertrophy in Corin-Deficient Mice: Observations in a Transgenic Model of Preeclampsia

Background

Preeclampsia increases the risk of heart disease. Defects in the protease corin, including the variant T555I/Q568P found in approximately 12% of blacks, have been associated with preeclampsia and cardiac hypertrophy. The objective of this study was to investigate the role of corin and the T555I/Q568P variant in preeclampsia-associated cardiac alterations using genetically modified mouse models.