Movie 1. Video of voltage cascades across the mouse brain from Movie 1 in the paper “Voltage Imaging of Waking Mouse Cortex Reveals Emergence of Critical Neuronal Dynamics” published December 10, 2014 in The Journal of Neuroscience.

Genetically encoded voltage indicator proteins have the potential to move the electrophysiological investigation of brain function into a new era by enabling both small scale and large scale investigation of electrical signaling in brains. Research reported recently in the paper “Voltage Imaging of Waking Mouse Cortex Reveals Emergence of Critical Neuronal Dynamics” (published December 10, 2014 in The Journal of Neuroscience) used optical imaging of a genetically encoded voltage indicator expressed in layer 2/3 neurons of the mouse cortex to investigate the relationship between small scale and large scale signal processing in the cerebral cortex.

Microelectrode recordings usually focus on the activity of a single cell, tens of microns in size, and provide fine temporal resolution down to the sub-microsecond level. In contrast, electroencephalography (EEG) records data from across large expanses of cortical tissue with high temporal resolution but poor spatial resolution, making it difficult to impossible to discern small scale signal processing characteristics. Hi spatial resolution across an entire brain may be achieved using functional Magnetic Resonance Imaging (fMRI) but with a severe loss of temporal resolution. The technique used in the study under review, optical imaging of a genetically encoded voltage indicator expressed in layer 2/3 neurons, enables capturing electrical activity across an entire hemisphere of the mouse cerebral cortex down to a 33 x 33 micrometer individual pixel resolution at a temporal resolution down to 20 milliseconds.

It’s unclear how results using this new technique will map to results gathered using older methods. In particular, how is a single neuron response represented in the data gathered at these resolutions? Does it matter or is the mass action of neurons more relevant at the recorded spatiotemporal resolution? Whatever the answers to these questions may be, this new technique has provided the research team with the ability to measure electrical signal processing in layer 2/3 cortex at a relatively small scale and then to use averaging techniques to look at the same signals at much lower resolutions. In this way, they could investigate affects of scale on signal processing in the cerebral cortex.

The signal processing paradigm used in this experiment was very simple. Measure cortical responses from mice beginning while they were under pentobarbital anesthesia, through their emergence from the anesthetic, until they were awake and at rest. Under all states, the research team saw cascades of activity sweep across the cerebral cortex (see Movie 1 above). However, the nature of the cascades depended on the state of the animal.

Across all brain states the researchers saw small, locally isolated and short-lived cascades more often than large cascades. In the anesthetized state, however, very large cascades of activity were often seen that were not usually seen in other brain states. Regional variations in cascade statistics (the probability of observing a cascade of a particular size) under anesthesia displayed clear anatomical boundaries associated with known sensory and motor regions. These boundaries disappeared during recovery phase until you’d be hard pressed to see clear anatomical distinctions in the cascade statistics in the awake animal.

The authors of this paper were looking for evidence to help them answer two questions: 1) Are cortical dynamics the same or different at different scales of extent? Or are cortical dynamics independent of scale? and 2) Does activity in the mammalian cortex adhere to the rules of critical dynamics?

I will address these questions in light of their findings in my next post.