Dynamic DNA methylation regulates neuronal intrinsic membrane excitability.

Epigenetic modifications, such as DNA cytosine methylation, contribute to the mechanisms underlying learning and memory by coordinating adaptive gene expression and neuronal plasticity. Transcription-dependent plasticity regulated by DNA methylation includes synaptic plasticity and homeostatic synaptic scaling. Memory-related plasticity also includes alterations in intrinsic membrane excitability mediated by changes in the abundance or activity of ion channels in the plasma membrane, which sets the threshold for action potential generation.

DNA methylation regulates neuronal glutamatergic synaptic scaling.

Enhanced receptiveness at all synapses on a neuron that receive glutamatergic input is called cell-wide synaptic upscaling. We hypothesize that this type of synaptic plasticity may be critical for long-term memory storage within cortical circuits, a process that may also depend on epigenetic mechanisms, such as covalent chemical modification of DNA. We found that DNA cytosine demethylation mediates multiplicative synaptic upscaling of glutamatergic synaptic strength in cultured cortical neurons.

Transcriptional and epigenetic regulation of Hebbian and non-Hebbian plasticity.

The epigenome is uniquely positioned as a point of convergence, integrating multiple intracellular signaling cascades into a cohesive gene expression profile necessary for long-term behavioral change. The last decade of neuroepigenetic research has primarily focused on learning-induced changes in DNA methylation and chromatin modifications. Numerous studies have independently demonstrated the importance of epigenetic modifications in memory formation and retention as well as Hebbian plasticity.

Interindividual Variability in Stress Susceptibility: A Role for Epigenetic Mechanisms in PTSD.

Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by intrusive and persistent memories of a psychologically traumatic event that leads to significant functional and social impairment in affected individuals. The molecular bases underlying persistent outcomes of a transient traumatic event have remained elusive for many years, but recent studies in rodents have implicated epigenetic modifications of chromatin structure and DNA methylation as fundamental mechanisms for the induction and stabilization of fear memory. In addition to mediating adaptations to traumatic events that ultimately cause PTSD, epigenetic mechanisms are also involved in establishing individual differences in PTSD risk and resilience by mediating long-lasting effects of genes and early environment on adult function and behavior.

Collagen-elastin ratio predicts burst pressure of arterial seals created using a bipolar vessel sealing device in a porcine model.

Background: Bipolar electrosurgical devices are used to generate rapid and efficient hemostasis in a wide range of surgical procedures. Of the factors that influence seal integrity, vessel (artery) diameter has been considered the most important variable. In this study we hypothesized that the relative ratio of the components that form the seal (collagen and elastin) determine the degree of vessel distensibility and play an equally important role in defining seal strength.