Search

The past two decades have seen an explosion in our understanding of the origin and development of the midbrain dopamine system. Much of this work has been focused on the aspects of dopamine neuron development related to the onset of movement disorders such as Parkinson's disease, with the intent of hopefully delaying, preventing or fixing symptoms. While midbrain dopamine degeneration is a major focus for treatment and research, many other human disorders are impacted by abnormal dopamine, including drug addiction, autism and schizophrenia. Understanding dopamine neuron ontogeny and how dopamine connections and circuitry develops may provide us with key insights into potentially important avenues of research for other dopamine-related disorders. This review will provide a brief overview of the major molecular and genetic players throughout the development of midbrain dopamine neurons and what we know about the behavioral- and disease-related implications associated with perturbations to midbrain dopamine neuron development. We intend to combine the knowledge of two broad fields of neuroscience, both developmental and behavioral, with the intent on fostering greater discussion between branches of neuroscience in the service of addressing complex cognitive questions from a developmental perspective and identifying important gaps in our knowledge for future study. [ABSTRACT FROM AUTHOR]

Prediction error plays an important role in modern associative learning theories. For example, the omission of an expected event (surprise) can enhance attention to cues that accompany those omissions, such that subsequent new learning about those cues is more rapid. Many studies from our laboratories have demonstrated that circuitry that includes the amygdala central nucleus (CeA), the cholinergic neurons in the substantia innominata/nucleus basalis region and their innervation of the posterior parietal cortex is critical for this surprise-induced enhancement of attention in learning. We recently showed that midbrain dopamine neurons, known to code prediction error, are also important for surprise-induced enhancement of learning through their interaction with CeA. The present study examined whether in rats the communication between the substantia nigra pars compacta (SNc) and CeA is critical only at the time of surprise, for example to detect prediction error information, or is also needed to maintain and later express that information as enhanced learning. All animals received unilateral CeA lesions and unilateral cannula implants targeting the SNc located contralateral to the lesioned CeA. As the SNc–CeA connections are mainly ipsilateral, inactivating SNc contralateral to the lesioned CeA provided transient blockage of SNc and CeA communication. The results show that SNc–CeA communication is critical for processing prediction error information at the time of surprise, but neither SNc nor SNc–CeA communication is necessary to express that information as enhanced learning later. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cells are a valuable resource for transplantation, yet our ability to profile xenografts is largely limited to low-throughput immunohistochemical analysis by difficulties in readily isolating grafts for transcriptomic and/or proteomic profiling. Here, we present a simple methodology utilizing differences in the RNA sequence between species to discriminate xenograft from host gene expression (using qPCR or RNA sequencing [RNA-seq]). To demonstrate the approach, we assessed grafts of undifferentiated human stem cells and neural progenitors in the rodent brain. Xenograft-specific qPCR provided sensitive detection of proliferative cells, and identified germ layer markers and appropriate neural maturation genes across the graft types. Xenograft-specific RNA-seq enabled profiling of the complete transcriptome and an unbiased characterization of graft composition. Such xenograft-specific profiling will be crucial for pre-clinical characterization of grafts and batch-testing of therapeutic cell preparations to ensure safety and functional predictability prior to translation., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)