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Rationale: The heart is mainly innervated by the sympathetic nervous system that is involved in the fight or flight response. Sympathetic neurons (SNs), whose cell bodies are placed in the stellate and superior cervical ganglia, mediate the main physiological mechanism increasing the frequency and force of cardiac contraction through release of norepinephrine. Recently, we have reported that SNs regulate heart trophism through stimulation of β2 adrenergic receptors and repression of muscle specific ubiquitin ligases (i.e. Murf1 and Atrogin1) but not much is known about the effects of SNs on sarcomeres. Nerve growth factor (NGF) released by the myocardium controls cardiac innervation by SNs after binding to its receptor (TrkA) and is required for neuronal survival. Thus, bidirectional coupling between SGNs and the heart takes place: the heart needs to be coupled to the SNs to receive norepinephrine stimulation for an efficient increase in heart contraction, and conversely, SNs are coupled to the heart for neurotrophic stimulation that is required for neuronal viability. However, whether a cell-cell interaction occurs in the SN-heart coupling is not known. An interaction between the muscle and the neuron that has been well described both in terms of function and structure, is the neuro-muscular junction (NMJ), characterized by membrane thickenings, acetylcholinergic receptor clustering, reduced intermembrane space (70-50 nm) and neurotrophin release by the postsynaptic myocyte (e.g. NT3, NT4). Considering the interaction between the SNs and the heart (neuro-cardiac junction, NCJ), this study aims i) to evaluate the effects of anterograde SN stimulation on sarcomeric structures, ii) to determine whether specific cellular structures are present at the SN/Cardiomyocyte (CM) contact site, iiI) to investigate the role of SGN/CM contact in NGF-mediated signaling. Results: To analyze changes in sarcomere structure, cultured CMs were treated with adrenergic stimuli (clenbuter