(Image caption: Fluorescent microphotograph of neurons. The green dye stains for a specialized synaptic protein and the red dye stains for actin, the polymeric protein that forms microfilaments and is a major component in the cytoskeleton. Credit: Adam Wegner, Webb Lab / Vanderbilt)

New insight into how brain makes memories

Every time you make a memory, somewhere in your brain a tiny filament reaches out from one neuron and forms an electrochemical connection to a neighboring neuron.

A team of biologists at Vanderbilt University, headed by Associate Professor of Biological Sciences Donna Webb, studies how these connections are formed at the molecular and cellular level.

The filaments that make these new connections are called dendritic spines and, in a series of experiments described in the April 17 issue of the Journal of Biological Chemistry, the researchers report that a specific signaling protein, Asef2, a member of a family of proteins that regulate cell migration and adhesion, plays a critical role in spine formation. This is significant because Asef2 has been linked to autism and the co-occurrence of alcohol dependency and depression.

“Alterations in dendritic spines are associated with many neurological and developmental disorders, such as autism, Alzheimer’s disease and Down Syndrome,” said Webb. “However, the formation and maintenance of spines is a very complex process that we are just beginning to understand.”

Neuron cell bodies produce two kinds of long fibers that weave through the brain: dendrites and axons. Axons transmit electrochemical signals from the cell body of one neuron to the dendrites of another neuron. Dendrites receive the incoming signals and carry them to the cell body. This is the way that neurons communicate with each other.

As they wait for incoming signals, dendrites continually produce tiny flexible filaments called filopodia. These poke out from the surface of the dendrite and wave about in the region between the cells searching for axons. At the same time, biologists think that the axons secrete chemicals of an unknown nature that attract the filopodia. When one of the dendritic filaments makes contact with one of the axons, it begins to adhere and to develop into a spine. The axon and spine form the two halves of a synaptic junction. New connections like this form the basis for memory formation and storage.

(Image caption: Fluorescent microphotograph of neurons that shows filapodia extending out from dendrite. Credit: Webb Lab / Vanderbilt)

Autism has been associated with immature spines, which do not connect properly with axons to form new synaptic junctions. However, a reduction in spines is characteristic of the early stages of Alzheimer’s disease. This may help explain why individuals with Alzheimer’s have trouble forming new memories.

The formation of spines is driven by actin, a protein that produces microfilaments and is part of the cytoskeleton. Webb and her colleagues showed that Asef2 promotes spine and synapse formation by activating another protein called Rac, which is known to regulate actin activity. They also discovered that yet another protein, spinophilin, recruits Asef2 and guides it to specific spines.

“Once we figure out the mechanisms involved, then we may be able to find drugs that can restore spine formation in people who have lost it, which could give them back their ability to remember,” said Webb.

Confession:  I like to think that after the Citadel party, if you choose the lively + calm sequence, the booby traps Garrus and Zaaed set up actually kill a couple of keepers when the Reapers take the Citadel. Or maybe this giant explosion just goes off randomly, sending glass shards flying everywhere, and shorts out the Catalyst for a bit. Just to piss it off. Microfilaments laid across the glass in a 5x5 grid. First line of defense in home security. Maybe a keeper wants to get in the hot tub? BIG MISTAKE!

The Cytoskeleton

So, we’re moving on to finding out how cells divide, but before we do that you need a bit of background on an important structure in the cell: the cytoskeleton.

This is an internal, 3D network of protein fibres that supports the cell’s shape, helps regulate functions, and acts like highways for intracellular transport (such as moving organelles). You can essentially think of it as the cell’s skeleton and muscles combined into one system.

There are three main kinds of fibres that make up the cytoskeleton, each constructed from different monomers:

Thin filaments (also known microfilaments or actin filaments): These fine, thread-like protein fibres are the thinnest kind of filaments. About 5-7 nanometres across, they’re made up of globular actin monomers—the most abundant cellular protein—and are wound in a helical shape. Their functions include carrying out cell movements, interacting with the protein responsible for muscle contraction, and pinching apart animal cells during cytokinesis.

Intermediate filaments: About 10 nanometres in diameter, these are pretty diverse and made up of different kinds of fibrous monomers like keratin, twisted together like a cord. Intermediate filaments mainly help maintain cell shape by bearing tension.

Thick filaments (also known as microtubules): About 20-25 nanometres across, these are long, hollow cylinders formed by alpha and beta tubulin. Thick filaments are the main scaffold of the cell, determining the cell’s shape and playing a key role in transport, acting like train tracks for vesicles and organelles to move around. They’re also incredibly important in mitosis because they form the spindle that separates the chromosomes. 

(a) Thick filaments, (b) thin filaments, © thin filaments. Source: Wikimedia Commons

Further resourcesArticle at Nature and Video at Educationportal