Although the synaptic physiology of the amygdala has been studied with single neuron recordings, the properties of the networks between the various nuclei have resisted characterization because of the limitations of field recording in a neuronally diffuse structure. We addressed this issue in the rat amygdala complex in vitro by using a photodiode array coupled with a voltage-sensitive dye. Low-intensity single pulse stimulation of the lateral amygdala nucleus produced a complex multi-phasic potential. This signal propagated to the basolateral nucleus and the amygdalostriatal transition zone but not to the central nucleus. The local potential, which depended on both synaptic responses and activation of voltage-dependent ion channels, was reduced in amplitude by the non-N-methyl-D-aspartate (non-NMDA) glutamate receptor antagonist 6,7-dinitroquinoxaline (DNQX) and reduced to a lesser extent by the NMDA glutamate receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV). We next characterized the less complex signals that propagated to more distal regions with or without the addition of the GABA receptor antagonist bicuculline (BIC). BIC alone greatly increased the signal propagation and permitted activation of previously silent areas within the amygdala. DNQX blocked signal propagation to amygdala regions outside of La, even in the presence of BIC, whereas D-APV had minimal effects on these distal signals. These data represent several novel findings: the characterization of the multi-component potential near the site of stimulation, the gating of signal propagation within the amygdala by GABAergic inhibition, the critical role of non-NMDA receptor-mediated depolarization in signal propagation, and the lack of a role for NMDA receptors in maintaining propagation.

According to the International Lymphoma Radiation Oncology Group, pneumonitis occurs in about 25% of patients receiving fractionated TBI. For conventional treatments, lung sparing is obtained using physical blocks that also block the adjacent tissues, and therefore, decrease target coverage. The purpose of this work is to develop a robust treatment planning workflow for TBI using a multi-isocentric VMAT technique to provide lung sparing without compromising target coverage. Materials/Methods: Four anonymized full body CT imaging sets with 1 cm slice thickness were used. A script in Varian Eclipse v13.7 was developed in-house to optimize field arrangement. The algorithm evaluates the body contour and user origin to generate two beam configurations: a head first VMAT based plan for upper body coverage using 4 isocenters and a total of 8 or 10 full arcs; and a feet first AP/PA matched multiisocentric arrangement that covers the lower extremities of the patient. PTV was the entire body cropped 5 mm from the patient surface and extended 3 mm into the organs at risk (OARs). PTV coverage goal was set to V100%>90% and D2cc<130%. Two plans were generated. Plan A only considered the lungs as an OAR with dose constraints Dmean<9Gy and D0.03cc<120%. In addition to the lungs, Plan B also restricted the dose to the kidneys with the constraints Dmean<11Gy and D0.03cc<120%. Plans were generated with the same optimization template for each approach and calculated using the AAA algorithm (5 mm grid, 6MV photons) to a total dose of 1320 cGy in 8 fractions. Results: Planning constraints were met for all cases, with 3 cases using 8 arcs and one case requiring 10 arcs due to larger anatomy. For plan A, an average mean lung dose of 846.6 cGy and a mean target coverage of V100%Z94.4% were obtained. For Plan B, the lung doses and PTV coverage were reproduced and the average Dmean to the kidneys was 1082.4 cGy. Dosimetry for both plans is summarized in the enclosed table. Body volume from CT imaging ranged between 56599 and 90932 cm 3 , maximum lateral separation between 44 and 61 cm, and maximum craniocaudal separation between 155 and 183 cm. Conclusion: VMAT-based TBI can accomplish significant lung dose sparing while maintaining target coverage without the need for compensation or blocks. Eclipse scripting facilitates and standardizes beam configuration for a multi-isocentric treatment eliminating variability and suboptimal placement regardless of the patient anatomy. In addition, the established beam configuration allows sparing of additional OARs, such as the kidneys, for patients at additional risk or to minimize long term complications.

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