Here’s a schematic of the rat brain showing some of the relevant structures, as well as dopamine pathways coming from the VTA and the substantia nigra (image reproduced from the lab page of Dr. Jeremy Clark here at UW; 6). Many other connections and neurotransmitter systems are not pictured**.
Most of the approaches used in the past to study reward-based feeding have been invasive or involved chemical manipulations that complicate the interpretation of results as they pertain to natural behavior. Enter the recent study. Dr. Hoch and colleagues used a twist on an interesting technique called MEMRI*, which allowed them to monitor cumulative neuron activity over a 7-day period in freely behaving rats. Rats were divided into two groups, and each received a different diet:
- Normal rat chow plus crushed rat chow.
- Normal rat chow plus crushed potato chips. Score!
Rats, like humans, love potato chips, and as expected group #2 group ate a lot of chips over the 7-day period, significantly increasing total calorie intake.
The changes in brain activity were striking. Here’s a cool image from the paper. Regions in red showed increased activity, while regions in blue showed reduced activity:
The NAc, perhaps the most iconic reward/addiction-related structure in the brain, was strongly activated in group #2. Other structures related to reward also lit up, including the dorsal striatum and LH. Neuron activity in the VTA ‘paradoxically’ was suppressed. This could probably be explained by someone who knows more about the VTA than I, but I do think it’s worth noting that some neurons signal by firing less rather than more.
This is where the findings become even more interesting. Group #2 experienced a decrease in the activity of brain regions that regulate energy homeostasis, including the arcuate nucleus in the hypothalamus and the nucleus tractus solitarius in the brainstem, consistent with the possibility that consumption of a hyperpalatable food may have ‘shut down’ the mechanisms that normally prevent excess food intake. We can’t take this line of reasoning too far, because each of these structures contains a variety of cell types doing different things, and looking at global activity patterns doesn’t necessarily give us a clear idea of what’s going on at the cellular level. But it’s an interesting hint nevertheless.
Also, they found changes in brain regions related to sleep and wakefulness, which is interesting given the emerging links between circadian rhythms, sleep, food intake and obesity.
Since humans have essentially the same brain structures as rats, and these structures serve similar purposes, this is probably roughly what happens in the human brain during habitual consumption of highly palatable junk food. The reward system gets revved up, and the regions that would normally oppose food intake and body fatness may be shut down as a consequence.
* Manganese-Enhanced Magnetic Resonance Imaging. The basic idea is that when neurons fire strongly, they take in calcium, which acts as an intracellular second messenger. Normally, this calcium is transported out of the cell after it has done its job. However, manganese can also get in through these channels, but it isn’t efficiently exported afterward. So if researchers experimentally increase the concentration of manganese in the brain, it accumulates in neurons in proportion to the amount each neuron has fired. This accumulated manganese can then be detected by MRI. MEMRI has been around for a while, but the current authors improved on it by using a gradual low-dose infusion rather than a large acute injection, which tends to make the animals sick.
** Besides dopamine, neurons in the reward system use endorphins, orexins, cannabinoids, glutamate, GABA, and other signals. Connections between the VTA, the NAc, and the LH are central to food reward, though other areas are also important. These connections are mediated primarily by dopamine, orexin, GABA, and glutamate signals.