(2011) presents an intriguing hypothesis on the modulation of morphine analgesia by heterodimerization of DORs with MORs. It pulls together and confirms prior observations and extends them to provide an explanation for how DORs modulate morphine actions. It represents a significant step forward in our understanding of the basic mechanisms underlying various aspects of opioid tolerance. Like most good science, it also raises a number of issues that need to be addressed in the future. Some of these involve trans-isomer purchase MOR-1 splice variants, both the full length ones that can potentially dimerize with DORs and the

truncated single TM ones that may have actions similar to those seen with MORTM1-TAT. However, it is important to remember that tolerance learn more is like a tug of war, with heterodimerization representing only a single person pulling on the rope. “
“Because neurons communicate electrically, neuroscience has traditionally relied on measurements of the membrane potential using electrodes.

But because electrodes are mechanically invasive, there are scant data on how different parts of a neuron interact or how assemblies of neurons communicate. As an example of this limitation, it is not possible to measure the electrical properties of dendritic spines, the primary sites for excitatory input in the brain, with electrodes because spines are simply too small for current electrodes. Electrical recordings also have significant limitations in studies of the thousands Thymidine kinase of cells that form neuronal microcircuits, where only highly invasive electrode arrays can be used to record the ensemble’s electrical activity. Optical techniques, however, seem to be an ideal solution for measuring membrane potentials, for both spines and circuits, since they are relatively noninvasive and could work both at low and high magnification. While voltage imaging in neuroscience has a long history and has

provided many significant advances in neuronal biophysics and circuit function (reviewed in Cohen, 1989 and Cohen and Lesher, 1986), our belief is that it has not yet achieved its full potential, particularly for the study of mammalian preparations. As Sherlock Holmes argued, to understand a situation one needs to evaluate not only was has happened but also what has not happened. In this case, we find it useful to compare current voltage imaging methods with calcium imaging to understand what could be missing. For example, calcium indicators are very sensitive ( Tsien, 1980) and have custom-tailored spectroscopic properties ( Grynkiewicz et al., 1985). They can be noninvasively loaded into neurons ( Tsien, 1981) and can be genetically encoded ( Miyawaki et al., 1997).