PALO ALTO, Calif. — Not enough is known about specific neurotransmitters' effects to enable engineers to build electronic brains. As a result, blueprints of the brain have been meticulously dissected and cataloged, but no one knows how to read these blueprints. However, researchers at Stanford University have begun to determine precisely what circuits neurotransmitters enable in the brain, thereby permitting engineers to read the brain's blueprint and eventually emulate it electronically.

"What we have discovered could be a template for unraveling how all the neurotransmitters work," said professor David Prince, principal scientist on the project.

Motor control in the brain is coordinated by mapping the "on" and "off" control signals for muscles to horizontal areas of the cerebral cortex. For instance, you could make the fingers of the hand twitch by touching the areas corresponding to it on the surface of the cerebral cortex. These horizontal surface areas on the cortex, such as for the muscles controlling speech, are cataloged and well-known, but each area is further organized into cortical columns, neurons that descend into the deeper parts of the brain to form circuitry specific to that muscle-enabling a pianist to push the keys softly or vigorously, rather than just on or off.

Further, coordination among different circuits, such as playing a guitar string by plucking with one hand and depressing a fret with the other, requires that these horizontal regions form synchronization circuits with both hand areas on the cortex. Such horizontal circuits must also be in synchronization with vertical circuits. Decoding all these possible circuits requires identifying the specific effect of each neurotransmitter on each type of neuron.

Essentially, Stanford University researchers are beginning to translate the brain's blueprint by revealing what circuits the neurotransmitter acetylcholine enables, including the equivalent of a previously unsuspected electronic negation operation. In particular, researchers found that acetylcholine inhibits horizontal interconnections among cortical columns, while simultaneously inhibiting neurons within the columns, effectively switching off vertical circuitry.

The key found by the Stanford research group led by Prince was that the neurotransmitters, in particular acetylcholine, have different effects depending on the exact type of receptor and type of neuron. The group found that acetylcholine simultaneously enhanced horizontal circuits and inhibited vertical circuits by attaching two different types of receptor cells in each group of neurons.

Technically, the horizontal neurons use muscarinic acetylcholine receptors (mAChR), whereas the bipolar vertical neurons have nicotinic acetylcholine receptors (nAChR), enabling acetylcholine to have the different effects on the different neurons. Acetylcholine attaches to the horizontal mAChR neurons causing them to release less gamma-aminobutyric acid (GABA) thereby turning on horizontal communication. Whereas in the vertical bipolar cells acetylcholine attaches to the nAChR receptor causing more GABA to be produced thereby inhibiting vertical communication.

Prince cautioned, however, about the imminent arrival of a Rosetta stone for reading the brain's whole blueprint. First the effects of the other neurotransmitters have to be discovered for each of the various types of receptors, then the various effects have to be mapped onto the real anatomical databases for the brain's regions. "Before we can begin to understand how large chunks of the brain work, we will have to put our studies of anatomy and neuron responses together with our new understanding of neurotransmitters," he said.