1. Lateral habenula as a source of negative reward signals in dopamine neurons Masayuki Matsumoto & Okihide Hikosaka (2007) Presented by Miranda Stewart

2. Reward System Dopamine neurons in the substantia pars compacta respond to and predict reward. Lateral habenula project to the substantia pars compacta. The lateral habenula has been implicated in anxiety, stress, pain, avoidance learning, attention, human reward processing, and psychosis.

3. The Experiment 2 Rhesus Macaques, activity of 49 LHb neurons recorded (37 in monkey L, 12 in monkey E) Reward-biased visual saccade task

4. The Experiment

5. Results

7. Lateral habenula was excited with no reward and inhibited by reward. Dopamine neurons showed opposite effect. Both showed response predictively (during target phase, not reward phase) Both showed large reward on/off reactions which declined rapidly after the first trial

8. Response to Reward/No Reward

9. Response to reward size

10. Causal Relationship Unrewarded trials – excitatory response of habenula neurons occurs before inhibition of dopamine neurons Rewarded trials – inhibition of habenula neurons occurs after excitation of dopamine neurons Need to test whether habenula neurons affect dopamine reward responses

11. The Experiment Delivered electrical stimulation to LHb while recording response of 22 dopamine neurons Showed strong inhibition 10-40 ms after onset Stimulation of the surrounding area was ineffective

12. Results

13. Dopamine neurons inhibited more strongly during no-reward trials were inhibited more strongly during stimulation of LHb Excitation during reward trials showed no correlation with stimulation of LHb

14. Conclusions Habenula neurons respond to reward/ no- reward and unexpected appearance/ disappearance of reward Involved in negative reward processing Needs future research with other conditioning and reward procedures Still unknown where the negative reward information comes from