Paired Electrical Pulse Trains for Controlling Connectivity in Emotion-Related Brain Circuitry

Neurostimulation therapies for psychiatric disorders often have limited clinical efficacy. The limited efficacy might arise from a mismatch between therapy and disease mechanisms. Mental disorders are believed to arise from communication breakdown in distributed brain circuits, and thus altering connectivity between brain regions might be an effective way to restore normal brain communication. Synchronized neural oscillations (coherence) and synaptic strength are two common measures of brain connectivity. In this work, we developed an electrical stimulation method for altering narrow-frequency-band (theta, 5-8 Hz) coherence and synaptic strength. We tested this method in a circuit between infralimbic cortex (IL) and basolateral amygdala (BLA), which is broadly implicated in fear regulation. 6 Hz pulse trains were delivered into IL and BLA with various inter-train lags. These paired trains induced long-lasting synaptic strength change and a brief coherence enhancement in the IL-BLA circuit. This enhancement was specific to the "top-down" (IL-to-BLA) direction, and only occurred when the IL and BLA pulse trains had a relative lag of 180° (83 ms). Since the IL-BLA connection is known to be highly relevant to fear regulation, this method provides a tool to study the relationship between brain connectivity and fear behaviors. Further, it may be a new approach to study the relative roles of synaptic strength and oscillatory synchrony in brain network communication.