Hippocampal ripple-contingent training accelerates trace eyeblink conditioning and retards extinction in rabbits

There are at least two distinct oscillatory states of the hippocampus that are related to distinct behavioral patterns. Theta (4–12 Hz) oscillation has been suggested to indicate selective attention during which the animal concentrates on some features of the environment while suppressing reactivity to others. In contrast, sharp-wave ripples (∼200 Hz) can be seen in a state in which the hippocampus is at its most responsive to any kind of afferent stimulation. In addition, external stimulation tends to evoke and reset theta oscillation, the phase of which has been shown to modulate synaptic plasticity in the hippocampus. Theoretically, training on a hippocampus-dependent learning task contingent upon ripples could enhance learning rate due to elevated responsiveness and enhanced phase locking of the theta oscillation. We used a brain–computer interface to detect hippocampal ripples in rabbits to deliver trace eyeblink conditioning and extinction trials selectively contingent upon them. A yoked control group was trained regardless of their ongoing neural state. Ripple-contingent training expedited acquisition of the conditioned response early in training and evoked stronger theta-band phase locking to the conditioned stimulus. Surprisingly, ripple-contingent training also resulted in slower extinction in well trained animals. We suggest that the ongoing oscillatory activity in the hippocampus determines the extent to which a stimulus can induce a phase reset of the theta oscillation, which in turn is the determining factor of learning rate in trace eyeblink conditioning.