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Dopamine neuron responses to aversive stimuli (not so diverse after all) Mark Ungless Department of Zoology University of Oxford Midbrain dopamine neurons play a key role reward processing Midbrain dopamine neurons play a key role reward processing Evidence comes from: Studies of dopamine release (microdialysis and voltammetry) Behavioural Pharmacology Molecular Biology Human fMRI and Electrophysiological studies of firing activity Is the dopamine signal selective for reward? Dopamine neurons are preferentially activated by reward (e.g., Schultz & colleagues) Is the dopamine signal selective for reward? Dopamine neurons are preferentially activated by reward (e.g., Schultz & colleagues) or Dopamine neurons are activated by all salient, attention-grabbing stimuli (e.g., Redgrave, Prescott & Gurney, 1999) How do dopamine neurons respond to aversive, non-rewarding stimuli? Reward hypotheses predict that dopamine neurons will either not respond to, or be inhibited by, aversive stimuli. How do dopamine neurons respond to aversive, non-rewarding stimuli? Reward hypotheses predict that dopamine neurons will either not respond to, or be inhibited by, aversive stimuli. Salience hypotheses predict that dopamine neurons will be excited by aversive stimuli How do dopamine neurons respond to aversive, non-rewarding stimuli? Reward hypotheses predict that dopamine neurons will either not respond to, or be inhibited by, aversive stimuli. Salience hypotheses predict that dopamine neurons will be excited by aversive stimuli Although most dopamine neurons are inhibited by aversive stimuli, around 25% of dopamine neurons are excited by aversive stimuli. How do dopamine neurons respond to aversive, non-rewarding stimuli? Reward hypotheses predict that dopamine neurons will either not respond to, or be inhibited by, aversive stimuli. Salience hypotheses predict that dopamine neurons will be excited by aversive stimuli Although most dopamine neurons are inhibited by aversive stimuli, around 25% of dopamine neurons are excited by aversive stimuli. Are we sure they are all dopamine neurons? Actually they’re putative dopamine neurons Actually they’re putative dopamine neurons So, are they all dopamine neurons? A recently-identified population of non-dopaminergic neurons in VTA brainslice with broad action potentials (Cameron et al., 1998). So, are they all dopamine neurons? A recently-identified population of non-dopaminergic neurons in VTA brainslice with broad action potentials (Cameron et al., 1998). Maybe neurons that are excited by aversive stimuli are not dopaminergic? Conclusions Dopamine neurons are uniformly inhibited by aversive, non-rewarding stimuli. Conclusions Dopamine neurons are uniformly inhibited by aversive, non-rewarding stimuli. A population of non-dopaminergic neurons are excited by aversive stimuli. Conclusions Dopamine neurons are uniformly inhibited by aversive, non-rewarding stimuli. A population of non-dopaminergic neurons are excited by aversive stimuli. These results support the reward hypothesis of dopamine neuron function. Conclusions Dopamine neurons are uniformly inhibited by aversive, non-rewarding stimuli. A population of non-dopaminergic neurons are excited by aversive stimuli. These results support the reward hypothesis of dopamine neuron function. How does this relate to dopamine release? But what about dopamine release? Microdialysis studies typically show slow increases in dopamine release induced by aversive stimuli. But what about dopamine release? Microdialysis studies typically show slow increases in dopamine release induced by aversive stimuli. Is this an opponent process? Offset of aversive stimuli can be rewarding. Tanimoto et al., 2004
