How is that you can remember, in detail, your first day of school, but can't recall what you ate for breakfast this morning? New research from a group at Hopkins may provide the answer. Their study, published last month in Cell, shows that emotion enhances memory by means of a single molecule, norephineprhine, whose concentration in the brain increases during stressful situations.
Because the brain's memory-storage capabilities are finite, distinguishing between significant and insignificant memories is a biological necessity. Evolutionarily advantageous information should be given priority over less relevant facts - for example, the color of a poisonous berry compared to the color of a stranger's eyes.
It has been well-established that stress is a key factor enhancing learning and, subsequently, memory. (Once the vomiting and hallucinations are over, you'll likely remember that berry's color.) In some cases, the relationship between stress and memory can go awry, as in post-traumatic stress disorder. Generally though, it's effective in filtering out most of the trivial information that assails us each day.
At the cellular level, memory is nothing more than a strengthening, over time, of certain connections between neurons. Termed long-term potentiation, or LTP, there are various ways this can happen.
The most well-understood version occurs when a given neuron becomes more sensitive to signals - in the form of molecules called neurotransmitters - sent by a neighboring neuron. Primarily this involves increasing the number of neurotransmitter-specific receptors present at the synapse, the junction between two neurons where neurotransmitters are released and received.
Many scientists have hypothesized that stress somehow causes more receptors to be brought to the synapse during LTP and hence boosts retention of emotional memories. Nonetheless, until now the exact molecular mechanism has remained a mystery.
Several pathways have been proposed, and, while differing in their details, all start with one molecule: norepinephrine (NE). During stressful situations, neurons in the brainstem release NE into several other areas of the brain, including the hippocampus, the center of memory formation.
Through a multi-step chemical pathway, NE ultimately activates a protein kinase called PKA. A protein kinase is the cellular equivalent of a highlighter; it tags other proteins by adding to them one or more highly energetic phosphate groups. A tagged protein is more recognizable to other molecules. In the case of memory formation, the proteins in question are, in fact, receptors.
The crux of the debate until now has been over which type of receptor PKA tags. The Hopkins team, led by Richard Huganir and working with researchers from the Cold Spring Harbor Laboratory on Long Island, N.Y., focused on one of the more promising candidates, AMPA receptors.
AMPA receptors bind to glutamate, the most common excitatory neurotransmitter in the central nervous system. When glutamate binds to an AMPA receptor, the receptor allows positively charged ions to flow into the cell. The neuron's charge thus becomes more and more positive until, at a certain point, the influx of positive ions becomes self-perpetuating and eventually causes the neuron to signal the next cell.
With more AMPA receptors at the synapse, more glutamate can bind, more positive ions flow in, and a faster, stronger signal is passed on to other neurons. In other words, NE indirectly lowers the threshold for the long-term potentiation of a neuronal connection.
The researchers hypothesized that PKA preferentially tags an AMPA receptor subunit called GluR1. Proving this involved creating genetically engineered mice with a mutated version of GluR1. Compared with normal mice, the mutated mice showed an impairment in learning and memory when NE levels in the brain were elevated (that is, during emotionally-charged events).
Nonetheless, the researchers still saw some long-term potentiation of hippocampal cells in the mutant mice, suggesting that there are other mechanisms, yet to be discovered, by which NE can influence the strengthening of synapses along the path to memory formation.
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