How does brain chemistry change when we learn/forget something?

Work at CalTech by Mary Kennedy is trying to map the complex chemistry that happens at the synapses between neurons in our brain when we learn, forget or lose interest in something, or "surrender" retaining a memory, like during meditation. As we take in the world around us, learn, and form memories, the synapses between neurons are constantly being modified. Some get stronger, while others shrink or get weaker. The network of enzyme-regulated chemical reactions that control these modifications is very complex as this part of the map shows.

One of the main theories in this area is Hebbian theory introduced in 1949. This states that "When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased." This is commonly stated as "Cells that fire together, wire together." It attempts to explain "associative (Hebbian) learning", in which simultaneous activation of cells leads to pronounced increases in synaptic strength between those cells. Conversely, cells that stop firing together, will "unwire".

Much of meditation is focused on unwinding/undoing "engrams" or neural networks from old memories and associations and perhaps forming new ones. Over the past 30 years, researchers have pieced together an understanding of the regulatory pathways and enzymes involved in controlling and modifying synaptic activity, and they’ve created “cartoons”—maps showing how the various components of the pathways interact.

Looking at the cartoons, with their tangles of crisscrossing arrows connecting proteins and enzymes, the complexity of the network becomes apparent. Researchers have worked out many of the players involved and how they interact to modify synapse strength. But they still know little about the dynamics of the network and how the processes are activated over time and under different circumstances.

“We know how little strings of enzymatic processes can get activated,” Kennedy says. “But we don’t have very good ways of asking what happens when, say, 20 of these processes are interacting and you tweak one or two.”

Kennedy is putting together an experimental method that will enable her to capture such “snapshots in time.” She recently acquired a device that can freeze brain tissue samples as quickly as one second after electrical stimulation. Previously, Kennedy says, “we had no way of putting recording-electrodes into a brain slice, stimulating, and then freezing it solid or stopping it within a second.”

“That will let us map out the changes that happen in this large network immediately after a synchronized synaptic input,” Kennedy says. “That means we’ll be able to measure much more globally how these complex pathways interact with each other—which ones are more important at early stages, and which ones come in later—all of which has been very difficult to understand.”
She hopes that she’ll be able to use her new method to identify synaptic pathways that may be relevant to mental illnesses and Alzheimer’s disease. (As well as to understand how meditation "works" to unwind certain highly problematic neural networks.)

The complete synaptic chemistry cartoon map: