Top Five Reasons to Map Neural Circuits
Recently, we asked a renowned professor in neurobiology, “Why do you feel neural circuits are important to study?”
Quick with an answer, he said, “Because everyone else is!”
His quip revealed some truth, in that it captured a major ongoing movement in neuroscience.
So why are so many neuroscientists now pushing the boundaries to study neural circuits?
Here are our thoughts:
Genes and environment converge at the level of neural circuits. We know a lot about the individual genes involved in neural transmission, and how individual neurons respond as a consequence of certain stimuli. But we know much less about how groups of neurons work together to produce the complex behaviors we witness everyday, in animals, other humans, and in ourselves. Neural circuits operate at the mesoscale, between molecular-level interactions and behavioral or cognitive output.
- Behavior and cognition arise via interactions between neural circuits. Our brains predict our environments through a miraculous process of adaptation so that we can interpret and navigate the maze of objects and beings amongst which we move in our world. The computations happen at the level of interacting circuits, making studying them essential. To get at this problem, we need integrated methods for measuring and manipulating neural circuits at a very large scale, say for thousands of neurons at a time in the context of behavior or cognition.
Neural circuits are likely to be conserved across species. This is especially true for brain circuits within the limbic regions mediating our emotions, memories, and all the subcortical structures which work under the hood to keep our body and mind humming along. Thus, if we can identify a signature at the level of neural circuits in mice, that could go a long way to revealing a biomarker in humans which can be noninvasively imaged. This may allow neuroscientists to then stratify individuals for risk to a disease. For example, in the case of post traumatic stress disorder, certain neural circuit signatures identified in mice could also reveal a vulnerability to stress in humans.
Neural circuits may be the best way to identify disease biomarkers. When it comes to diagnosing and treating human neurobehavioral and psychiatric diseases, the science is highly imperfect. There’s a tremendous amount of heterogeneity within each category of disease, and many conditions share symptomatology, to the point that treatment can be uncertain and a process of trial and error for the patient and doctor. But many brain disorders are coming to be understood as a neural circuit dysfunction. Thus, neural circuits have a good chance of serving as signatures for specific neurobehavioral and psychiatric conditions. It’s also worth mentioning that certain diseases, like tauopathies, propagate in the brain along highways provided by neural circuits. Thus an understanding of neural circuits may become an important aspect of therapeutic intervention to prevent neurodegenerative diseases.
- We can now! The goal is to measure and manipulate neural circuit dynamics across and within brain areas in a single experiment, while a subject behaves, with the added value of knowing the identity and connectivity of the recorded neurons. This goal could only have been realized within the last decade. Through genetic tools expressing GCaMPs combined with miniature microscopes, we can now monitor the activity of large numbers of neurons during naturalistic behavior. We also now have the ability to manipulate neural activity through optogenetic tools while simultaneously measuring neural activity via integrated imaging and optogenetic systems. These types of innovative methods provide powerful ways to link neural circuitry to their functions in the brain.
Studying neural circuits offer the potential to transform our understanding of how the brain works and provide critical insights relating complex brain functions to human behavior, cognition and disease.
What are your thoughts about why neural circuits are important to study?