Effects of single-cell stimulation on the local neural network
Final Report Abstract
The human brain contains an estimated one hundred billion neurons, and the cerebral cortex alone accounts for roughly 15 billion nerve cells. Even the brain of a rat, weighing a few grams only, contains about 20 million cortical neurons and 200 million neurons in total. Given these vast numbers, it is tempting to dismiss the role of individual neurons as unimportant for network operation. Yet, recent studies have demonstrated that brief (~200 ms) electrical activation of a single cortical neuron can be sufficient to evoke a behavioral reaction in trained rats. However, the mechanism by which the activity of a single neuron can modify the state of the entire brain is largely unexplored, although such knowledge is crucial to understand the operations of neural networks in general. In order to achieve a better understanding of the effects of single-cell stimulation on local neural network activity, we developed new stimulation protocols to drive individual neurons with high temporal precision. Specifically, we managed to achieve tight control over the spiking output of neurons through a refinement of the juxtacellular stimulation technique. Inspired by recent findings, we hypothesized that the temporal pattern of neural activity (more specifically, the regularity of action potential firing) determines the degree by which postsynaptic targets of the stimulated neuron are affected. We thus imprinted two different patterns of neural activity onto single cortical neurons in anesthetized transgenic mice expressing a fluorescent protein coupled to Arc, an immediate-early gene whose degree of expression correlates well with neural activity. One set of neurons was driven to exhibit regular spiking at 5 Hz, and another set of neurons was driven to exhibit irregular spiking at 5 Hz with exponentially distributed inter-spike intervals. The amount of neural activity induced in neighboring cells was determined by quantifying the strength of the dVenus-fluorescence signals in brain slices post mortem. Overall, we find that the number of induced spikes is closely coupled to the strength of the fluorescence signal in the stimulated cell. Also, irregular stimulation induces stronger fluorescence signals than regular stimulation. The degree to which postsynaptic targets of the stimulated cells are more strongly activated through irregular than regular spiking remains to be determined in the near future.
