Tue, May 14, 2013 - Page 9 News List

Mapping a path through the dense forest of the human brain

By Javier DeFelipe

Our brains are like a dense forest — a complex, seemingly impenetrable terrain of interacting neurons that mediates cognition and behavior. The great challenge is to uncover its mysteries, that is, to find out how the neurons are structured and mutually connected. How close are we to that goal?

In general, the exchange of information between the billions of neurons that make up the neuronal forest takes place through two types of highly specialized structures: chemical synapses (the majority) and so-called gap junctions (a substrate of one class of electrical synapse). Chemical synaptic transmission involves the release of specific molecules, neurotransmitters, which diffuse through the intercellular space and interact with specific receptors located on an adjacent neuron.

In the electrical transmission mediated by gap junctions, the plasma membranes of adjacent neurons are separated by a gap of about 2 nanometers (two-billionths of a meter), but contain small channels (the gap junctions) that connect the cytoplasm of the adjoining neurons, permitting the diffusion of small molecules and the flow of electric current.

The major problem when analyzing the brain is the extreme complexity of its synaptic connections. A very dense network of processes occupies the space between the cell bodies of the neurons, neuroglia (cells that support and protect neurons) and blood vessels. This space (the neuropil) represents between 90 percent and 98 percent of the volume of the human cerebral cortex, with an estimated 1 billion synapses per cubic nanometer of neuropil.

As if that did not make the brain mappers’ job difficult enough, a wide variety of synaptic relationships has been observed. And a neurotransmitter may diffuse and act not only on other synaptic contacts, but also on extrasynaptic receptors. Likewise, not all electrical transmission is mediated by gap junctions, and these forms involve different specialized structures.

In addition, electrical interactions take place between closely apposed neuronal elements without obvious membrane specializations.

Furthermore, it has been proposed that glial cells are involved in information processing through their bidirectional signaling with neurons. And we now know that the activity of neuronal circuits is strongly influenced by neuromodulators (such as dopamine, serotonin and acetylcholine), which are secreted by a small group of neurons and diffuse through large regions of the nervous system. Neurohormones, released by neurosecretory cells, also have an effect on many brain regions via the circulatory system.

Nonetheless, we are beginning to find our way through the forest.

The brain’s wiring — its “synaptome” — is the anatomical substrate for a variety of functions that require information to be communicated rapidly from one point to another. The neuronal circuits involved in reflexes are a typical example — relatively simple, fast, automatic actions that occur at a subconscious level. Other, much more complex functions related to the synaptome include information processing in large but discrete circuits in the sensory and motor systems and in the brain regions associated with language, calculation, writing and reasoning.

However, the modulatory systems act on multiple neuronal circuits and brain areas. This diffuse action is related to the overall moods and states of the brain (for example, attentiveness, sleep and anxiety).

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