Bidirectional Switch Of The Valence

Optogenetics

Media Cited1. Tonegawa picture2. Optogenetics mouse3. Histology picture and experimental procedure picture 4. Memory trace: HMB300 lecture 3 slide 395. Emotional valence6. Tonegawa video7. Optogenetics motor8. Immunohistochemistry 9. Place preference apparatus

Bidirectional switch of the valence associated with a hippocampal contextual memory engram

Immunohistochemistry

Their experimental procedure.

Place Preference/ Place Aversion

Memory Trace

Susumu Tonegawa's Laboratory

This experiment was testing if dorsal dentate gyrus (DG) or basolateral amygdala (BLA) were able to cause a switch in the emotional valence of context based fear or reward memories. The researchers in this experiment virally infected mice with ChR2 (channelrhodopsin) in either their DG or BLA, which are known to encode context or fear memories, respectively. The infected neurons possess a special promoter that will only express channelrhodopsin when mice have no doxycycline in their diet, and in neurons that are actively encoding the memory. Mice underwent shock dependent fear conditioning or reward conditioning (by being exposed to a female mouse) without doxycycline in their diet. Two days after conditioning trials, while on doxycycline, neurons were light activated while the mice were in a certain area of a new environment using a place preference/ place avoidance paradigm. Fear conditioned mice showed aversive response to this area when both DG and BLA labeled neurons were light activated (OptoPA). Consequently, reward conditioned mice were attracted to this area when both DG and BLA labeled neurons were light activated (OptoPP). Mice whose DG or BLA had initially been conditioned with fear or reward were re-exposed to a condition of opposite valence (shock/female mouse) while under optogenetic stimulation. After re-conditioning, DG ChR2 fear conditioned neurons showed an attractive response in OptoPP. Reward conditioned DG ChR2 neurons displayed aversive response in OptoPA. BLA labeled neurons did not undergo this switch in emotional valence. Using immunohistochemisty, researchers also showed that optogenetic stimulation of DG conditioned neurons activated BLA neurons expressing early gene fluorescence proteins. If mice had undergone a trial to reverse the associated valence, there was significantly less BLA fluorescence under DG optogenetic activation. These results suggest that DG neurons are able to encode a conetxt dependent emotional valence that is reversible, and this reversal may involve different connections to the BLA.

Emotional Valence

The Power of Optogenetics

Using ChR2 Expressing Neurons