Distinct hippocampal engrams control extinction and relapse of fear memory

Learned fear often relapses after extinction, suggesting that extinction training generates a new memory that coexists with the original fear memory; however, the mechanisms governing the expression of competing fear and extinction memories remain unclear. We used activity-dependent neural tagging to investigate representations of fear and extinction memories in the dentate gyrus. We demonstrate that extinction training suppresses reactivation of contextual fear engram cells while activating a second ensemble, a putative extinction engram. Optogenetic inhibition of neurons that were active during extinction training increased fear after extinction training, whereas silencing neurons that were active during fear training reduced spontaneous recovery of fear. Optogenetic stimulation of fear acquisition neurons increased fear, while stimulation of extinction neurons suppressed fear and prevented spontaneous recovery. Our results indicate that the hippocampus generates a fear extinction representation and that interactions between hippocampal fear and extinction representations govern the suppression and relapse of fear after extinction.We thank J. Dunsmoor for comments on the manuscript. A.F.L. was supported by NIH F31 MH111243 and NIH T32 MH106454. S.L.S. was supported by PD/BD/128076/2016 from the Portuguese Foundation for Science and Technology. Research supported by NIH DP5 OD017908 and New York Stem Cell Science (NYSTEM) C-029157 to C.A.D., NIH R01 MH102595 and NIH R21 EY026446 to M.R.

Dorsolateral Striatum Engagement Interferes with Early Discrimination Learning

Summary: In current models, learning the relationship between environmental stimuli and the outcomes of actions involves both stimulus-driven and goal-directed systems, mediated in part by the DLS and DMS, respectively. However, though these models emphasize the importance of the DLS in governing actions after extensive experience has accumulated, there is growing evidence of DLS engagement from the onset of training. Here, we used in vivo photosilencing to reveal that DLS recruitment interferes with early touchscreen discrimination learning. We also show that the direct output pathway of the DLS is preferentially recruited and causally involved in early learning and find that silencing the normal contribution of the DLS produces plasticity-related alterations in a PL-DMS circuit. These data provide further evidence suggesting that the DLS is recruited in the construction of stimulus-elicited actions that ultimately automate behavior and liberate cognitive resources for other demands, but with a cost to performance at the outset of learning. : What is the contribution of the DLS in early discrimination learning? Bergstrom et al. show using in vivo optogenetics, fluorescence in situ hybridization, and brain-wide activity mapping that silencing the DLS facilitates early discrimination learning, drives activity in a parallel PL-DMS circuit, and preferentially recruits the DLS “direct” output pathway. Keywords: striatum, reward, goal-directed, habit, optogenetics, plasticity, cognition, Ar