Journal of neurogenetics最新文献

The genetic basis of complex trait like learning and memory have been well studied over the decades. Through those groundbreaking findings, we now have a better understanding about some of the genes and pathways that are involved in learning and/or memory. However, few of these findings identified the naturally segregating variants that are influencing learning and/or memory within populations. In this special issue honoring the legacy of Troy Zars, we review some of the traditional approaches that have been used to elucidate the genetic basis of learning and/or memory, specifically in fruit flies. We highlight some of his contributions to the field, and specifically describe his vision to bring together behavior and quantitative genomics with the aim of expanding our knowledge of the genetic basis of both learning and memory. Finally, we present some of our recent work in this area using a multiparental population (MPP) as a case study and describe the potential of this approach to advance our understanding of neurogenetics.

In many animals, the establishment and expression of food-related memory is limited by the presence of food and promoted by its absence, implying that this behavior is driven by motivation. In the past, this has already been demonstrated in various insects including honeybees and adult Drosophila. For Drosophila larvae, which are characterized by an immense growth and the resulting need for constant food intake, however, knowledge is rather limited. Accordingly, we have analyzed whether starvation modulates larval memory formation or expression after appetitive classical olfactory conditioning, in which an odor is associated with a sugar reward. We show that odor-sugar memory of starved larvae lasts longer than in fed larvae, although the initial performance is comparable. 80 minutes after odor fructose conditioning, only starved but not fed larvae show a reliable odor-fructose memory. This is likely due to a specific increase in the stability of anesthesia-resistant memory (ARM). Furthermore, we observe that starved larvae, in contrast to fed ones, prefer sugars that offer a nutritional benefit in addition to their sweetness. Taken together our work shows that Drosophila larvae adjust the expression of learned and naïve choice behaviors in the absence of food. These effects are only short-lasting probably due to their lifestyle and their higher internal motivation to feed. In the future, the extensive use of established genetic tools will allow us to identify development-specific differences arising at the neuronal and molecular level.

Sleep plays an important role in regulating plasticity. In Drosophila, the relationship between sleep and learning and memory has primarily focused on mushroom body dependent operant-learning assays such as aversive phototaxic suppression and courtship conditioning. In this study, sleep was increased in the classic mutant rutabaga (rut²⁰⁸⁰) and dunce (dnc¹) by feeding them the GABA-A agonist gaboxadol (Gab). Performance was evaluated in each mutant in response to social enrichment and place learning, tasks that do not require the mushroom body. Gab-induced sleep did not restore behavioral plasticity to either rut²⁰⁸⁰ or dnc¹ mutants following social enrichment. However, increased sleep restored place learning to rut²⁰⁸⁰ mutants. These data extend the positive effects of enhanced sleep to place learning and highlight the utility of Gab for elucidating the beneficial effects of sleep on brain functioning.

Dopamine provides crucial neuromodulatory functions in several insect and rodent learning and memory paradigms. However, an early study suggested that dopamine may be dispensable for aversive place memory in Drosophila. Here we tested the involvement of particular dopaminergic neurons in place learning and memory. We used the thermogenetic tool Gr28bD to activate protocerebral anterior medial (PAM) cluster and non-PAM dopaminergic neurons in an operant way in heat-box place learning. We show that activation of PAM neurons influences performance during place learning, but not during memory testing. These findings provide a gateway to explore how dopamine influences place learning.

I knew Troy for nearly 15 years, and in that time I don't recall hearing any childhood stories like those in seemingly every personal statement I've read from aspiring scientists or medical students. No stories about hours spent gazing at an anthill. I don't recall hearing about shelves crowded with insects collected on Styrofoam, or animal skulls kept in a shoebox under his bed. If these collected crania existed, it was more likely because Troy was a crack shot with a pellet gun than a need to know adaptations in the dentition of local squirrel populations. I don't recall hearing about science projects taken to the Iowa State Capitol to share with politely interested legislators. But I do recall hearing about spending the entirety of the daylight hours in the summer, with his brother Doug, finding where the crappie were biting. About crystal clear water on a lake in Minnesota that you didn't quite need to know the exact location of, just in case you were thinking of going and plundering the walleye within. I definitely heard about triumphs as a starting lineman not only for his high school football team, but the mighty Norse of Luther College. I heard about summer warehouse jobs in sweltering Iowa Julys. And I saw, firsthand, love and commitment and family. Troy's story demonstrates that the finest scientists are not just cultivated in narrow STEM curricula that begin at age 5. They are just as likely to be football-playing fishermen, fathers, husbands, and friends who can navigate an operant conditioning paradigm during the week, and dance a polka and produce a magnificent smoked pork shoulder on Saturday. Nature and an independent spirit and a little bit of mischief is a different kind of Magnet school. And it gave us truly one of the best.

In the 1990s, prominent biologists and journalists predicted that by 2020 each of us would carry a genome card, which would allow physicians to access our entire genome sequence and routinely use this information to diagnose and treat common and debilitating conditions. This is not yet the case. Why not? Common and debilitating diseases are rarely caused by single-gene mutations, and this was recognized before these genome card predictions had been made. Debilitating conditions, including common psychiatric disorders, are typically caused either by rare mutations or by complex interactions of many genes, each having a small effect, and epigenetic, environmental, and microbial factors. In such cases, having a complete genome sequence may have limited utility in diagnosis and treatment. Genome sequencing technologies have transformed biological research in many ways, but had a much smaller effect than expected on treatments of common diseases. Thus, early proponents of genome sequencing effectively "mis-promised" its benefits. One reason may be that there are incentives for both biologists and journalists to tell simple stories, including the idea of relatively simple genetic causation of common, debilitating diseases. These incentives may have led to misleading predictions, which to some extent continue today. Although the Human Genome Project has facilitated biological research generally, the mis-promising of medical benefits, at least for treating common and debilitating disorders, could undermine support for scientific research over the long term.

Optogenetics has revolutionized the field of neuroscience. Within the last decades the development and use of optogenetics gained enormous importance for the identification of functional synaptic connections. Employing optogenetic tools in anatomically defined pathways offers a straightforward strategy to demonstrate neuronal sufficiency, even during state-dependent activity within a neuronal network. Hunger, thirst, fatigue or motivation each impact an animal's behavior and determine the internal states that tune neuronal pathways to generate context-appropriate actions. In particular, higher order brain processes, such as learning and memory formation, are often state-dependent and here optogenetics can provide the means to identify and investigate the neuronal pathways involved. Our aim with this article is to focus on the possibilities and limitations of optogenetic tools for dissecting the neuronal circuits underlying learning and memory formation in Drosophila, while emphasizing what these approaches can tell us about neuronal circuit function in general.

The Mushroom Body (MB) is the primary location of stored associative memories in the Drosophila brain. We discuss recent advances in understanding the MB's neuronal circuits made using advanced light microscopic methods and cell-type-specific genetic tools. We also review how the compartmentalized nature of the MB's organization allows this brain area to form and store memories with widely different dynamics.