Mapping Neural Circuits in Real Time

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When I was a graduate student in the 1990’s, and brave enough to raise my hand after a seminar, I asked the founder of neurophilosophy Patricia Churchland, “If we could record from every synapse of the human brain, would that tell us how consciousness emerges?” At the time, this suggestion bordered on preposterous, but her answer was decidedly optimistic that it was our best shot. Now, over 20 years later, neuroscience has moved into the decade of connectomics. Research proliferates with the expressed goal of mapping every connection in the brain. Institutes have formed around tackling the unimaginable task of identifying the 10,000 connections made by each of our 100 billion neurons. Some researchers hypothesize that not only is it critical we map the connections of the brain to better understand whole-brain function, but that we are our connectomes.The point Pat Churchland made in response to my question was that the key to investigating brain function was understanding more about neural circuits. Recently in an interview, she said of all the techniques she would wish for neuroscience, it would be methods to reveal neural circuits of behavior. “We kind of know how to access neurons and systems but we would like to access all of the dynamics in the circuitry. We still don’t know how neurons participate in the processing within the context of circuitry to give the systems level results.” While this is generally true, the field of neuroscience is making rapid headway on mapping neural circuits to their functions.

As with all of science, technological innovation drives advances in our ability to map the nervous system. The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, the large-scale project aimed to speed up the mapping of neural circuitry, offers scientists the opportunity to use innovative tools in order to get a “dynamic picture of the brain in action.” As brain mapping techniques improve, we’re able to visualize the circuitry of the brain in vivo in relationship to cognition and behavior in real time. Moreover, neuroscientists can image hundreds to thousands of neurons at a time. For example, genetically encoded calcium indicators allow calcium concentration changes associated with neural activity from thousands of individual neurons to be optically imaged simultaneously in intact nervous systems. Combined with miniature microscope technology, these kinds of in vivo imaging experiments can be carried out on rodents that are freely behaving, and can be repeated for weeks to months, taking neural circuit mapping to an unprecedented level of insight. Thus, not only can you identify specific neuronal signatures for hundreds of individual neurons, you can also map both their spatial location and activity patterns in real time, during free behavior. Using the analogy presented in “The Future of the Brain,” this is equivalent to identifying both the streets of a city and the traffic patterns through those streets during different times of the day, over the course of months.

Here at Inscopix, our goal is to foster a conceptual advance in the field of neuroscience through technological innovation that makes previously unimaginable brain mapping experiments possible. With our new “all-optical” neuromapping system, nVoke, neuroscientists can manipulate activity in defined populations of neurons using optogenetics while simultaneously measuring calcium dynamics in connected populations of neurons during active behavior. In these cutting-edge experiments researchers have optical methods for visualizing the circuitry of the brain with unprecedented spatial and temporal resolution, all in relationship to specific behavioral events, as they happen. In addition to advancing brain mapping technology, we care about time to result. Our approach is to create integrated, plug-and-play, real-time mapping solutions so you can get to publication in the fastest timeframe possible. Moreover, we validate our technologies through iterative refinement in partnership with the academic research community. As stated in a recent Neuron article, the neuroscience field is in an era of rapid technological innovation and moving toward the investigation of intact and living nervous systems. These kinds of experiments require neuroscientists to apply methods across disciplines. A close partnership between industry and the research community allows industry to focus on the job of improving technologies for usability and enhanced capability.

In this extraordinary time of real-time brain mapping, the neuroscience community benefits when all stakeholders come together to develop and apply novel technologies. While it’s unclear if we’ll ever truly understand the neural basis of consciousness, we will certainly bridge our mechanistic understanding of genetics and behavior at the level of neural circuits. Because, as I’ve heard many neuroscientists say, a better understanding of neural circuits holds the most promise for making inroads into neuropsychiatric therapeutics.

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