Successful tumor implantation was confirmed by transabdominal micro-ultrasound imaging on post-implantation day 11. Contrast enhanced micro-ultrasound imaging was done on days 14 and 21. Vascular endothelial growth factor receptor 2 targeted contrast agent was prepared by adding biotinylated anti-vascular endothelial growth factor receptor 2 monoclonal antibodies to streptavidin coated microbubbles. The targeted contrast agents were

injected via the retro-orbital route. We quantified intratumor perfusion, vascular endothelial growth factor receptor 2 endothelial expression and blood volume in real time.

Results: In the initial study intratumor perfusion data and vascular endothelial growth factor receptor 2 expression could only be measured in 10 of 14 mice (71%) due to motion artifact. We modified our technique by applying an elastic band over selleck inhibitor Selleck BAY 1895344 the lower abdomen to minimize body wall movement. After the modification complete images were acquired in all mice at 2 consecutive imaging sessions. Measurements were made of intratumor perfusion and in vivo vascular endothelial growth factor receptor 2 expression. No adverse effects occurred due to anesthesia or the ultrasound contrast agent.

Conclusions: Targeted

contrast enhanced micro-ultrasound imaging enables investigators to detect and monitor vascular changes in orthotopic bladder tumors. It may be useful for direct, noninvasive, in vivo evaluation of novel anti-angiogenesis therapeutic agents. With the modified technique target enhanced contrast ultrasound can be applied in an orthotopic bladder cancer model.”
“The tonically active neurons (TANS) are a population of neurons scattered sparsely throughout the striatum that show intriguing patterns

of firing activity during reinforcement learning. Following repeated pairings of a neutral stimulus with a primary reward, TANs develop a transient cessation of firing activity in response to the stimulus, termed the “”conditioned pause response.”" In tasks where specific cues are arranged to signal the probability of particular outcomes, the pause response to both cue and outcome may differ in ways that suggest the involvement of different inputs to the same neuron. Here we review the cellular properties of E7080 order cholinergic interneurons and describe the response to their afferents in terms of inducing TAN-like pauses in tonic firing. Recent work has shown that thalamostriatal inputs to cholinergic neurons transiently suppress firing activity via dopamine release. Because these pauses are initiated by subcortical pathways with limited sensory processing abilities, we propose that they are an ideal correlate for the pauses observed in TANs in response to cues signaling trial initiation. On the other hand, pauses that accompany outcome presentation contain higher-level information, including an apparent sensitivity to reward prediction error. Thus, these pauses may be mediated by cortical inputs to cholinergic interneurons.