Adverse Effects of Aromatase Inhibition on the Brain and Behavior in a Nonhuman Primate.

Breast cancer patients using aromatase inhibitors (AIs) as an adjuvant therapy often report side effects, including hot flashes, mood changes, and cognitive impairment. Despite long-term use in humans, little is known about the effects of continuous AI administration on the brain and cognition. We used a primate model of human cognitive aging, the common marmoset, to examine the effects of a 4-week daily administration of the AI letrozole (20 µg, p.o.) on cognition, anxiety, thermoregulation, brain estrogen content, and hippocampal pyramidal cell physiology. Letrozole treatment was administered to both male and female marmosets and reduced peripheral levels of estradiol (E2), but unexpectedly increased E2 levels in the hippocampus. Spatial working memory and intrinsic excitability of hippocampal neurons were negatively affected by the treatment possibly due to increased hippocampal E2. While no changes in hypothalamic E2 were observed, thermoregulation was disrupted by letrozole in females only, indicating some impact on hypothalamic activity. These findings suggest adverse effects of AIs on the primate brain and call for new therapies that effectively prevent breast cancer recurrence while minimizing side effects that further compromise quality of life.SIGNIFICANCE STATEMENT Aromatase inhibitors (AIs) are used as an adjuvant therapy for estrogen-receptor-positive breast cancer and are associated with side effects, including hot flashes, depression/anxiety, and memory deficits severe enough for many women to discontinue this life-saving treatment. AIs are also used by men, yet sex differences in the reported side effects have not been systematically studied. We show that AI-treated male and female marmosets exhibit behavioral changes consistent with these CNS symptoms, as well as elevated hippocampal estradiol and compromised hippocampal physiology. These findings illustrate the need for (1) a greater understanding of the precise mechanisms by which AIs impact brain function and (2) the development of new treatment approaches for breast cancer patients that minimize adverse effects on the brain.

An Electrophysiological Investigation of Power-Amplification in the Ballistic Mantis Shrimp Punch.

Mantis shrimp are aggressive, burrowing crustaceans that hunt using one the fastest movements in the natural world. These stomatopods can crack the calcified shells of prey or spear down unsuspecting fish with lighting speed. Their strike makes use of power-amplification mechanisms to move their limbs much faster than is possible by muscles alone. Other arthropods such as crickets and grasshoppers also use power-amplified kicks that allow these animals to rapidly jump away from predator threats. Here we present a template laboratory exercise for studying the electrophysiology of power-amplified limb movement in arthropods, with a specific focus on mantis shrimp strikes. The exercise is designed in such a way that it can be applied to other species that perform power-amplified limb movements (e.g., house crickets, Acheta domesticus) and species that do not (e.g., cockroaches, Blaberus discoidalis). Students learn to handle the animals, make and implant electromyogram (EMG) probes, and finally perform experiments. This integrative approach introduces the concept of power-amplified neuromuscular control; allows students to develop scientific methods, and conveys high-level insights into behavior, and convergent evolution, the process by which different species evolve similar traits. Our power-amplification laboratory exercise involves a non-terminal preparation which allows electrophysiological recordings across multiple days from arthropods using a low-cost EMG amplifier. Students learn the principles of electrophysiology by fabricating their own electrode system and performing implant surgeries. Students then present behaviorally-relevant stimuli that generate attack strikes in the animals during the electrophysiology experiments to get insight into the underlying mechanisms of power amplification. Analyses of the EMG data (spike train burst duration, firing rate, and spike amplitude) allow students to compare mantis shrimp with other power-amplifying species, as well as a non-power-amplifying one. The major learning goal of this exercise is to empower students by providing an experience to develop their own setup to examine a complex biological principle. By contrasting power-amplifiers with non-power-amplifiers, these analyses highlight the peculiarity of power amplification at multiple levels of analysis, from behavior to physiology. Our comparative design requires students to consider the behavioral function of the movement in different species alongside the neuromuscular underpinnings of each movement. This laboratory exercise allows students to develop methodology, problem-solving and inquisitive skills crucial for pursuing science.

First steps into the cloud: Using Amazon data storage and computing with Python notebooks.

With the oncoming age of big data, biologists are encountering more use cases for cloud-based computing to streamline data processing and storage. Unfortunately, cloud platforms are difficult to learn, and there are few resources for biologists to demystify them. We have developed a guide for experimental biologists to set up cloud processing on Amazon Web Services to cheaply outsource data processing and storage. Here we provide a guide for setting up a computing environment in the cloud and showcase examples of using Python and Julia programming languages. We present example calcium imaging data in the zebrafish brain and corresponding analysis using suite2p software. Tools for budget and user management are further discussed in the attached protocol. Using this guide, researchers with limited coding experience can get started with cloud-based computing or move existing coding infrastructure into the cloud environment.