1. Presented by Andrew Bubak
Attenuating GABAA Receptor Signaling in Dopamine Neurons Selectively Enhances Reward Learning and Alters Risk Preference in Mice Jones G. Parker,1 Matthew J. Wanat,2 Marta E. Soden,2 Kinza Ahmad,1 Larry S. Zweifel,2 Nigel S. Bamford,3,4 and Richard D. Palmiter1
Presented by Andrew Bubak

2. Goal Contribution of GABAA-R in DA neurons to behavior β3-KO mice
Decision making & risk preference
β3-KO mice

3. How did they do it? Locomotion Rotarod Performance T-maze
Instrumental Conditioning
Probabilistic Selection Task
Switching Task
Contextual Fear Conditioning
Two-way Active Avoidance

4. DA neurons in midbrain slices from β3-KO mice have reduced GABAA-R signaling
Whole-cell voltage-clamp recordings from VTA of midbrain slices (~45% decrease in freq.)

5. GABAA-R Function Testing Results
More significant at
larger amplitudes
Sensitivity of DA neurons to GABAergic
signaling is significantly decreased

6. Basal locomotor activity and rotarod performance are normal while morphine-induced locomotion is enhanced in β3-KO mice
Morphine = Enhancement in DA release

7. DA neurons have normal mEPSCs but non-DA neurons in the VTA of β3-KO mice smaller mIPSCs
Marked decrease in amplitude of
inhibitory events in non-DA
neurons of β3-KO
Suggest compensatory changes
in non-DA neurons of VTA in
β3-KO

8. β3-KO mice have increased DA release in the NAc in response to PPTg stimulation
Excitation of DA neurons by Glu and ACh is modulated by GABAA-R
Attenuating GABAA-R signaling disrupts inhibitory input to DA neurons
and augments excitability

9. β3-KO mice have enhanced acquisition but normal reversal or extinction during appetitive learning
Fixed Rew+ or Rew- arms
10 trials/day for 10days

10. β3-KO mice have enhanced acquisition but normal reversal or extinction during appetitive learning cont.
Unrewarded Lever Pressing
Given 7 days
High and Low Switched

11. β3-KO mice exhibit normal aversive learning
Shown that DA is required for
learning in active avoidance test

12. β3-KO mice are more risk-preferring in a probabilistic selection task

13. Final Thoughts
Information encoding reward probability is relayed to DA neurons, in part, through GABAergic inputs
Attenuating the sensitivity of DA neurons to GABA signaling may have disrupted the proper integration of information about reward probability at the level of DA neurons and increased the risk preference of β3-KO mice.

14. fin