RT Journal Article
SR Electronic
T1 Low-Frequency Stimulation Depresses the Primate Anterior-Cingulate-Cortex and Prevents Spontaneous Recovery of Aversive Memories
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8589
OP 8597
DO 10.1523/JNEUROSCI.6481-11.2012
VO 32
IS 25
A1 Oded Klavir
A1 Rotem Genud-Gabai
A1 Rony Paz
YR 2012
UL http://www.jneurosci.org/content/32/25/8589.abstract
AB Functional abnormalities in the dorsal-anterior-cingulate-cortex (dACC) underlie anxiety disorders and specifically post-traumatic stress disorder (PTSD). Promising and common behavioral approaches have limited effectiveness and many subjects exhibit spontaneous recovery of fear, as also evident in animal models following extinction training. Here, we use low-frequency stimulation (LFS), a protocol shown to induce long-term depression, with the aim of affecting synaptic plasticity induced by fear acquisition and extinction. We use aversive conditioning of either tone or visual stimuli paired with an aversive air-puff to the eye in a trace-conditioning paradigm. We find that LFS in the nonhuman primate (Macaca fascicularis) dACC, when combined with extinction training, was successful in preventing spontaneous recovery of the memory 24–72 h following extinction. We simultaneously record single-units and local-field-potentials across the dACC, and show that LFS gradually depressed evoked responses. Moreover, this decrease in neural excitability predicted the successful reduction of overnight spontaneous recovery on a day-by-day basis. Finally, we show that this effect occurs when using either visual or auditory modality as the conditioned stimulus, and that the reduction was specific to the conditioned modality. Our results suggest that the primate dACC is actively involved in maintaining the original aversive memory, and propose that a combination of LFS with behavioral therapy might significantly improve treatment in severe cases.