1) Measuring

If researchers are to make sense of the frenzy of electrical signals coursing the brain’s circuits, they will have to record simultaneously from as many neurons as is feasible. Today, they typically gauge neuronal activity by inserting metal electrodes in the brain, but this approach includes enormous challenges. Each electrode needs its own wire to execute the measured analogue signal ” the voltage change ” and also the signals can easily be lost or distorted when they travel along the wire to instruments which will then convert them into the digital signals required for analysis. Moreover, the wires have to be hair-thin to avoid tissue destruction. Advances in electrode technologies have seen the volume of neurons that researchers can document from double roughly every seven years within the last five decades, such that probes can now reach a few hundred neurons simultaneously; But the greatest challenge will require them to reach many more cells and in order to record higher-quality signals. That is starting to become possible with a new generation of neuroprobes constructed from silicon, which allows extreme miniaturization. Instruments such as analogue-to-digital converters can be carved from the same small piece of silicon as electrodes, so the vulnerable analogue signal doesn’t need to travel. A prototype ‘neuroprobe’ of this type was unveiled in February at the International Solid-State Circuits Conference in San francisco, California, by imec, a nanoelectronics research organization located in Leuven, Belgium. One-centimetre long in addition to being thin as a dollar bill, the probe packs in fifty-two thin wires and switches which neuroscientists can flip seamlessly between four hundred and fifty-six silicon electrodes.

When place in a mouse brain, for example, the electrodes dotted over the imec probe can span, as well as record from, all layers of the animal’s brain simultaneously, from the cortex to the thalamus in the brainstem. This might help neuroscientists to unpick the particular circuitry that connects them. This prototype could be scaled up, says Peter Peumans, director of bio- and nanoelectronics at imec. Within three years, he says, the neuroprobes could have up to 2, 000 electrodes plus more than 200 wires. But instead of just passively measuring electrical movement in neural circuits, examiners also desire to test what those circuits accomplish by activating them and watching the changes that occur within electrical activity and creature behavior. Each imec probe consists of four stimulating electrodes, and in upcoming models increased to 20 or possibly even more. But as recording and stimulating electrodes can interfere with each other researchers are also trying to stimulate neurons with light rather than electricity. These ‘optogenetic’ techniques typically involve placing light-sensitive ion-channel proteins called opsins in neurons, a laser light shone in to the skull through an optic fibre opens the channels triggering the neurons. One research team used optogenetics in mice, for example, to produce repetitive behaviors that are regarded as a model for obsessive-compulsive disorder. The next generation of optogenetic neuroprobes will include systems that can deliver light directly into the brain exactly where it is required, without the need for complicated optical fibers. In April, for instance, Michael Bruchas at Washington University in St Louis, Missouri, along with his team explained their wireless prototype: an optogenetic chip with light-emitting diodes which can be activated by a radio signal to trigger the opsins. Once the team implanted a chip into mice |which could stimulate the brain’s reward center the animals quickly learned to modify it on themselves by poking their noses in a hole proving that the chip worked and may even change behavior. The search for other natural or genetically engineered opsins that react to different wavelengths of light as well as might allow researchers to activate and test various aspects of| a circuit is on. Eventually, neuroprobes might not only regularly record from and stimulate hundreds or thousands of neurons in mice and non-human primates, but include sensors to identify neurotransmitters and measure physiological parameters like temperature, which can influence neuronal activity.

The future could bring far more radical methods. Some scientists have proposed the concept of nanometre-scale light-sensitive devices that could embed within the membranes of neurons, power themselves from cellular energy and wirelessly convey the activity of millions of neurons simultaneously. Another idea is to eliminate measuring devices and record the post-mortem trace left by an action potential as it passes through the brain instead . Kording is part of a team trying to do just this by exploiting DNA polymerase, the enzyme that cells use to construct DNA from its component bases. He and his colleagues have designed a synthetic DNA polymerase which, when surrounded by high amounts of calcium, inserts the wrong base in the artificial DNA strand it constructs. If this polymerase could possibly be added to neurons, then an action potential, which causes intracellular calcium levels to spike, would trigger errors within the DNA strand, and the time that this occurred could be determined retrospectively through the length and sequence of this DNA.