Altering function in cortical networks by short-latency, paired stimulation

Plasticity is a crucial component of normal brain function and a critical mechanism for recovery from injury. Numerous experimental studies have attempted to elucidate its underlying mechanisms under both in vitro and in vivo conditions. Short latency, associative pairing of presynaptic "trigger" spiking with stimulus-induced postsynaptic depolarization of a target neuron has been shown to lead to changes in the effectiveness of a stimulus applied to the presynaptic neuron. We have used similar methods to demonstrate changes in the statistically inferred functional connections among small groups of recorded neurons in rat sensorimotor cortex. These induced changes transcended simple changes in stimulus-evoked activity. Rather, they reflected a robust reorganization of network connectivity revealed by changes in the patterns of spikes in the cells' spontaneous discharge. We hypothesized that by strengthening the functional connections from trigger to target neurons, we might demonstrate a related behavioral change. To test this hypothesis, we trained rats to respond to a near-threshold, intracortical stimulus cue. Following 1-2 days of paired, short latency stimulation, the sensitivity of these rats to the cue was increased. The latency dependence and the timecourse of this effect were very similar to the corresponding parameters of the inferred connectivity changes in the first experiment. Such targeted connectivity changes may provide a tool for rerouting the flow of information through a cortical network, with profound implications for both rehabilitation and brainmachine interface applications.