Putative dopamine neurons that respond to aversive cues and stimuli

Dopamine neurons are weird. If you look at them up close the axons tend to originate not from the cell body but from a dendrite. They also (perhaps because of this) have a triphasic extracellular waveform that lasts longer than most other types of neurons. Oh, they also fire action potentials in response to reinforcers or reinforcer paired stimuli and are inhibited by aversive stimuli.

Or so it would seem.

Wang and Tsien (2011) recently provided evidence that there is a small but significant proportion (~25%) of dopaminergic neurons in the ventral tegmental area that fire in response to aversive stimuli. This could just mean that these neurons respond to salient cues (ala Berridge and Robinson). The remaining neurons are of the classic, reward activated type. Wang and Tsien convincingly show there are three recorded types of putative dopaminergic neurons, and that each type of neuron seems to synchronize with like type neurons. But before we get all excited there are three facts that make me somewhat incredulous.

First, the authors show that the putative dopamine neurons they record from have the characteristic electrophysiological signature associated with dopamine neurons. However, we know from other work that just because a neuron looks like it is dopaminergic doesn’t mean that it is, especially in the VTA. What's more, they did not show us the average waveform for these aversion activated dopamine neurons compared to the appetitive activated dopamine neurons. If they are the same great, but if not I am suspicious. Unfortunately, their technique of tetrode recording does not allow for post recording chemical identification of recorded neurons.

Second, the authors gave these mice apomorphine while recording from putative dopamine neurons. This is sometimes used as an identifier of dopamine neurons by those who do multi-wire recording. Apomorphine potently inhibits dopamine neurons. But not here. Here, putative aversion activated dopamine neurons were excited by apomorphine. Which makes me think they are not dopamine neurons.

Third, the authors recorded neurons while the animals were undergoing the aversive conditioning, i.e. while the mice were shook around. You could never hold onto a neuronal recording with a glass electrode under such a situation, so their claim that they are still recording from the same neurons before and after the stimulus ... I don't know I guess I have always been a little suspicious of multiwire recording.

Wang and Tsien may be on to something, but for myself I will need to see more evidence that they actually are recording from dopamine neurons before I go along with the idea that there are some that become active during aversive events.*

Wang DV, & Tsien JZ (2011). Convergent processing of both positive and negative motivational signals by the VTA dopamine neuronal populations. PloS one, 6 (2) PMID: 21347237

*And believe me I would like that. It would be easier to explain the results of some of my work if there are such dopamine neurons.