Nota dari Neuroscience grad student:

Storing explicit knowledge require a complicated series of processes in your brain.

Probably most importantly for learning, there are dedicated structures that store information when you first learn it. The main one is the hippocampus. These structures are responsible for creating separate, non-overlapping representations of everything you learn. But keeping your memories from overlapping and interfering with each other is difficult. And the more you learn at once, the more difficult this becomes. It is easy to store new information when your hippocampus is a mostly blank slate, but as you fill it up it becomes more difficult.

Your brain handles this by periodically exporting information out of the hippocampus and wiping the connections. The information is moved from the hippocampus to regions of your cortex with more storage capacity. This is mostly done while you are sleeping, and is probably one of the major reasons that we sleep at all. The hippocampus constantly creates new neurons to help act as an uncrowded substrate for new information coming in.

Those of you who have taken psychology or neuroscience courses have probably heard of patient HM, who had both of his hippocampi and the surrounding regions removed. From then on he could not store new memories, but could still remember everything he had learned before the operation. He kept the information he has already exported out to his cortex, but did not have the specialized structures he needed to quickly assimilate new knowledge.

There are also other factors.

Your frontal cortex has to inhibit distracting sensory information and unhelpful actions. The targets of these frontal cortex neurons could adapt to these constant inputs and require more and more inhibition over time. The inhibiting neurons can also deplete their stores of neurotransmitter and have to wait for more to be transported from the cell body several centimeters away.

The material you are learning has to be marked as important by the release of certain neuromodulators. The primary ones are probably acetylcholine (Ach) and norepinephrine (NE), and maybe dopamine. These chemicals have a number of effects: they allow neurons to change their connection strengths based on their inputs, they make your neurons more excitable, and they induce oscillations in some brain regions. These chemicals can be depleted, and so can the biochemical pathways they act through.

You are tired after learning new things because your brain wants you to sleep so it can replenish its biochemical and computational reserves.