The medial habenula is the medial division of the habenula, a nuclear complex of the epithalamus. It participates in a circuit projecting to the interpeduncular nucleus. The medial habenula and lateral habenula are neighboring anatomical divisions with different circuitry; results from one should not automatically be assigned to the other.[ref]
Habenular α5 nicotinic receptor subunit signalling controls nicotine intake by Christie D. Fowler and others. Originating 2011 article, medial-habenula/interpeduncular circuit and region-specific receptor manipulations.
A motivating experiment tested an inhibitory contribution to nicotine intake. Christie D. Fowler and colleagues found increased nicotine intake in mice lacking the α5 nicotinic acetylcholine receptor subunit. Re-expression of that subunit in the medial habenula rescued the altered intake phenotype; knockdown in the medial habenula of rats reproduced increased intake. The work distinguished nicotine's rewarding effects from an inhibitory effect appearing at higher tested doses.[ref]
Habenular α5 nicotinic receptor subunit signalling controls nicotine intake by Christie D. Fowler and others. Abstract: knockout, local rescue, rat knockdown and reward/inhibitory-signal distinction.
The rescue is particularly informative. A whole-animal mutation can alter many tissues and developmental processes. Restoring the relevant component in a specified region tests whether that regional circuit can account for an important part of the phenotype. Conversely, the comparison does not show that every medial habenula neuron has the same function or that the entire region is merely a nicotine-detector. The measured intake change is a result in specified rodent preparations, not a direct measurement of human smoking behavior or a clinical intervention.
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