Since the 1970s, human subjects that have undergone corpus callosotomy have provided important insights into neural mechanisms of perception, memory, and cognition. The ability to test the function of each hemisphere independently of the other offers unique advantages for investigating systems that are thought to underlie cognition. However, such approaches have been limited to mammals. Here we describe comparable experiments on an insect brain to demonstrate learning-associated changes within one brain hemisphere. After training one half of their bisected brains, cockroaches learn to extend the antenna supplying that brain hemisphere towards an illuminated diode after this has been paired with an odor stimulus. The antenna supplying the naïve hemisphere shows no response. Cockroaches retain this ability for up to 24 h, during which, shortly after training, the mushroom body of the trained hemisphere alone undergoes specific post-translational alterations of microglomerular synaptic complexes in its calyces.