Brady has long favored the idea that the cold-stable regions along axonal microtubules
act as “transportable microtubule organizing complexes” (Brady et al., 1984; Sahenk and Brady, 1987). Interestingly, TGF-beta inhibitor after years of controversy over whether or not axonal microtubules actually move, live-cell imaging on cultured neurons finally revealed that, in the axons of cultured neurons, microtubules unquestionably do move down the axon, but they do so only as very short fragments (Wang and Brown, 2002). Curiously, these mobile microtubules are not only very short, but they are also very stable, undergoing no detectable length changes during bouts of imaging. Mechanistic considerations are most consistent with these short microtubules moving by a sliding filament mechanism rather than as cargo, which is to say that the motor domain of the relevant molecular motor interacts
with the short mobile microtubule, whereas the cargo domain interacts with a longer stationary microtubule (Baas and Mozgova, 2012). One possibility is that, when a microtubule is thoroughly chopped by a microtubule-severing protein, what remains are the most stable regions RGFP966 of the microtubule—those enriched with polyaminated tubulin. It may be that it is the unique biochemical properties of polyaminated tubulin that not only provide for great stability of these fragments but also explain how certain motor proteins recognize them and how those motors know to transport them via a sliding filament mechanism. If this is the case, one could also imagine that a
much longer microtubule in an adult axon may contain multiple regions that are rich in polyaminated tubulin, thus enabling greater interaction with the relevant motor proteins. If this is the case, perhaps microtubules do not need to be so short in order to be transported in adult axons (Figure 1). Clearly, out there are many issues left on the table, but the latest work by Brady’s group has, after nearly three decades, made a much-needed leap toward understanding the nature of the cold-stable tubulin fraction. With rapid progress now underway, it is with some melancholy that many researchers will now remember washing that first pellet down the drain. ”
“The VS is thought to integrate incoming information to initiate motivated behavioral output (Mogenson et al., 1980). This complex process likely requires VS medium spiny projection neurons (MSNs) to differentially process incoming cortical and subcortical input. VS MSNs receive diverse excitatory input predominantly from the thalamus, hippocampus, basolateral amygdala, and prefrontal cortex (Britt et al., 2012; French and Totterdell, 2002), as well as rich dopaminergic input from the ventral midbrain (Swanson, 1982).