Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs

Pathology and Cardiotoxicity of the Epicardial Adipose Tissue

Intra-organ fatty infiltration is associated with end-organ damages and increased cardiovascular risk. Ectopic fat deposition occurs also within the heart and may cause a metabolic cardiomyopathy. Epicardial fat (EAT) can be considered ectopic fat accumulation of the heart. Epicardial fat and intra-myocardial triglycerides content are related. Excessive EAT can produce lipotoxic effects throughout an abnormal lipid deposition and fatty infiltration in the myocardium. As cardiomyocytes fat storage capacity is very limited, high levels of plasma lipids cause cardiac steatosis, hypertrophy, dysfunction, and ultimately failure, as observed in morbid obesity and uncontrolled diabetes. Due to its anatomical and functional vicinity to the myocardium, EAT can affect the morphology and function of all of the heart chambers. Increased epicardial fat has been largely associated with increased left ventricular mass, abnormal geometry, enlarged atria, and diastolic dysfunction. Multifactorial physical and biomolecular mechanisms can explain the effects of excessive EAT on the heart