All Posts

Over the past decades, neuroscientists have made great strides to map brain regions and allocate specific functions to them. Electrical recordings and lesioning studies have been essential for this task. However, most lesioning methods destroy areas larger than intended and may unintentionally remove connecting pathways between other distant regions. They also don’t give any clues about the types of neurons involved or whether their involvement is activating, inhibiting, or modulating. Viral vectors, in contrast, are considerably more versatile and specific in how they manipulate neuronal function, with far fewer side effects compared to lesioning methods -  they may be the key to further unraveling the mysteries of behavior.

The aim of behavioral neuroscience is to define brain areas that are linked to a certain behavior. It is a very old branch of science, dating back several hundred years, with historical ties to psychology and philosophy (the mind-body problem). Because of the availability of tools for genetic manipulations, mice have become the model of choice for many behavioral studies, though other organisms such as rats or zebrafish are also used. With the development of viral vectors, behavioral neuroscientists can now precisely control where and when certain genes are expressed to investigate their role in a specific behavior. This blog post will give an introduction to behavioral neuroscience, and address experimental design considerations used in all behavioral studies.

This post was contributed by Patrick Miller-Rhodes, a Ruth L. Kirschstein NRSA Predoctoral Fellow at University of Rochester Medical Center.

During development, complex genetic programs specify and assemble diverse arrays of neurons, forming the neuronal circuits that will later be refined through experience. However, studying the genetic underpinnings of these processes has been complicated by the lack of precise genetic tools for modulating gene expression in the central nervous system (CNS). To address this technological gap, a trio of recent papers describe the development of CRISPR activation (CRISPRa) tools for neuroscience, including transgenic mice, neuron-optimized viral vectors, and high-throughput screening approaches. Here, we’ll highlight these recent advancements and offer commentary on their application to neuroscience research.

Stochastic multicolor labeling is a popular technique in neuroscience and developmental biology. This type of cell labeling technique involves the introduction of a transgene construct containing fluorescent proteins (XFP) of different colors to label an organ or entire organism. Because each cell can have multiple copies of the transgene that will recombine independently, cells may acquire one of a variety of colors when a combination of XFP are expressed. Each cell remains the same color for its entire lifetime and daughter cells retain the same color, allowing for the fate mapping of cell populations over time. The ability to track single cell dynamics at the organism level has been made possible by tools that allow cells to become persistently fluorescent during development. Stochastic multicolor labeling systems, many based on Brainbow, now exist for a variety of species, cell types, and research applications.

The central nervous system (CNS) orchestrates complex processes enabling organisms to control their movements and behavior. These functions and others are controlled by collections of neurons that are intricately wired into circuits through synaptic connections (Shepherd, 2004). Understanding the structure and function of these neural circuits is essential for neuroscience research. The use of genetic tools for visualizing and perturbing circuits together with the development of methodologies to deliver genes to the CNS have recently made it much easier to map these neuronal networks.