Low-frequency stimulation of the ventral hippocampus facilitates extinction of contextual fear

Difficulties to treat fear-associated disorders, including posttraumatic stress disorder, are thought to result from dysfunction in fear extinction learning and/or memory. Animal studies on extinction modulation are therefore promising for the development of new treatments. Recent rat studies, including ones using low-frequency stimulation (LFS), have demonstrated that the ventral hippocampus (VH) modulates extinction memory. The present study explores whether the VH also modulates extinction learning. For this, rats were implanted with stimulating electrodes in the VH and experienced contextual fear conditioning, followed 6 or 24 h later by VH LFS and three sessions of extinction training. We found that, whatever the delay used (6 or 24 h), animals that received VH LFS displayed persistent low levels of freezing from the second extinction session, whereas control rats showed low levels of freezing only during the third session. In animals submitted to a stress condition (provoked by a single inescapable foot-shock followed by three sessions of situational reminders) prior to fear conditioning, VH LFS also reduced freezing levels, which, in contrast, remained high in control rats during the course of extinction training. These data suggest that LFS, targeting the VH, may be useful in reducing fear responses during extinction learning.