Sunday, March 13, 2011

The Brain's "Reward" Centre Also Responds to Fear

One of my pet hates in neuroscience is the propensity to attribute highly specialised functions to currently identified brain regions. If only it were that simple. This study, remarkable in its detailed analysis, again reminds us that the brain is not only a wonderful thing but an incredibly wonderfully complex thing.

It has long been known and studied that the ventral tegmental area(VTA), a rather small nucleus in the midbrain, is very much involved in "reward" processes. Illicit drug use very often involves the VTA dopamine neurons becoming rather active. Even marijuana, who some claim is not addictive, will involve activation of these neurons.  Note though that the abstract refers to a specific location in the VTA - the posterior region. These nuances in how these "cerebral modules" respond needs to be kept in mind. For example, we often read that the amygdala is a "fear center". For example, consider this recent news release which appears counter intuitive. In that news release, the so-called "fear centre" - amygdala appears to play a role in reducing anxiety. Note though that is very misleading to refer to a "fear centre". Neurons don't experience fear, we do! As the linked Wiki article states, the amygdala can be subdivided into many regions. For an excellent introduction to the amygdala, try reading "The Emotional Brain" by Joseph LeDoux, who pioneered important research into this region.

This study identified 3 types of dopamine neurons in the VTA. While Type 1 and Type 2 neurons did not respond to fearful events, actually decreasing their firing rates but with a rebound at the cessation of the fearful event, Type 3 neurons increased their firing rate. Thus ...

Moreover, the excitation duration of type-3 dopaminergic-like neurons also correlated with the duration of fearful events.
However I am puzzled by this and have to wonder if it points to error in identifying these Type 3 neurons:

Our pharmacological results revealed that the vast majority (96%; 23/24) of type-1 and type-2 putative dopamine neurons were significantly suppressed, while surprisingly the type-3 neurons (n = 9) otherwise showed excitation by apomorphine
The bods then went onto to test how these neurons responded to both positive and aversive events:

Neuronal activity recordings in these conditioned mice (after 1-week training) revealed that VTA putative dopamine neurons responded significantly to the conditioned tone that predicted a sugar pellet in the reward chamber (Figure 6D, left panel). Interestingly, the same VTA neurons also responded reliably to the same conditioned tone when it predicted free fall in the free fall chamber (Figure 6D, middle panel). When the same conditioned tone was delivered to mice in a neutral chamber that was not associated with any event, it did not produce significant changes in firing.
What this suggests is that these neurons in the VTA are not only responding to reward or adversity but also to the expectation that something in the environment is about to change. It would be interesting to see if any of these neurons would respond to innocuous environmental contingencies. I have a sneaking impression that what we are witnessing here is a general alerting function to a change in the environment, with different neurons providing information about the nature of the environmental change. This information is highlighted by a sentence in the closing paragraph of the paper:

These putative dopamine neurons respond to different negative events in a similar manner and more importantly, their temporal durations of dynamic firing changes are proportional to the durations of the fearful events.

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