In vivo Quantification of Neural Criticality and Complexity in Mouse Cortex and Striatum in a Model of Cocaine Abstinence

Abstract

Self-organized criticality is a hallmark of complex dynamic systems at phase transitions. Systems that operate at or near criticality have large-scale fluctuations or avalanches, the frequency and duration power of which are best fit with a power law revealing them to be scale-free and fractal, and such power laws are ubiquitous. It is an attractive concept in neuroscience since spiking avalanches are exhibited by neural tissue, and may underpin how minuscule events could scale up to circuits and provide adaptive psychobiological function. Much is yet to be understood about criticality in vivo in the healthy brain and in disorders such as addiction, as drugs may alter the critical state tuning to generate drug seeking and dysphoria. Thus, here a novel toolset was developed to use neural avalanches and their self-similarity, rather than power law fit slope exponents as is canonically done, to quantify criticality in a previously collected high-density electrophysiological in vivo corticostriatal dataset from a mouse model of early cocaine abstinence. During behavioral quiescence, in the prefrontal cortex but not ventral striatum of cocaine-dosed mice, it was found that critical tuning is enhanced compared to drug-free controls. Additionally, an empirical biological demonstration of complexity's theoretical correlation to criticality was shown in drug-free mice, was exponentially enhanced in drug-treated cortex, but was absent in the drug-treated striatum. As shown, quantifying criticality grants experimental support for the critical brain hypothesis and allows for statistical interpretation of inter-subject variability and development of further testable hypotheses in systems neuroscience.

Investigation of neural functional connectivity in thick acute mouse brain slices with novel multi-region 3D neural probe arrays

“…2e, right) are consistent with canonical multiregion in vivo recordings (1,34) suggesting the inherent viability of the technique, with the added benefit of being able to detect units at a signal threshold of 5x the background RMS band of 5.56±2.08 µV, orders of magnitude lower than typical in vivo recordings, similar to organoids; strikingly, this is near the 2.4 μV noise floor of the Intan chips themselves (Intan Technologies materials). This also allows us to achieve unit yields multiple times greater than current high-density neuroprobe methods with redundant channels (34,35). Finally, conventional neurophysiological knowledge suggests that positive-deflecting spikes are only a small percentage of single-unit responses, but in our hands, nearly 40% of the units we record are based on positive spikes, as in Figures 2b & 2c.…”

“…This represents a more realistic and physiological circuit-based target for ex vivo drug testing due to the ability to finely alter and record many more previously undetectable signals from the slice, and has many open paths of further experimentation. These include, but are not limited to, assays of transplanted and excised tissue, real-time multifiber circuit manipulation coupled to pharmacological testing, and in-depth neurophysics methods (35) and machine learning to characterize the slices in a manner heretofore unseen. There are yet unknown aspects to the progression of many neurodegenerative diseases which may become druggable targets, and this represents a strong method and platform to grasp the circuit and population correlates of established pharmacodynamics or the potentially silent phenotypes therein.…”