Published in: Berkeley Neuroscience News | April 29, 2015

By Kevin Doxzen

Perception is how we connect with the world around us: from grasping the steering wheel of a car to smelling a fresh cup of coffee in the morning. We often take these experiences for granted. Yet they are actually the result of a finely tuned coordination between complex neural networks in our brain.

Researchers have made substantial progress in understanding the different regions of this puzzling organ and their corresponding roles. One aspect of the brain’s function, however, has remained elusive: understanding how the coordinated firing of individual neurons can lead to the proper functioning of these larger neural regions.

Hillel Adesnik
Hillel Adesnik

“When the neural circuits no longer function properly you begin to have neurological and psychiatric disorders,” says Berkeley neuroscientist Hillel Adesnik. “The reason why we have very few effective treatments for these disorders is because we don’t understand the basis of how these circuits are working.”

Adesnik and his team are attempting to deconstruct the brain by analyzing small circuits and even single neurons. They hope to explain how groups of only a few cells can perform the neural computations necessary to generate perception and cognition.

To resolve these complex questions, Adesnik and his colleagues are focusing on the cerebral cortex. This outermost layer of the brain is necessary for several processes including memory, attention, and perception.

The researchers are employing both in vivo and in vitro experimental approaches. As a result, they are beginning to pinpoint specific pockets of neurons, known as microcircuits, and elucidate their role in the formation of percepts.

Optical tools such as Channelrhodopsin can be used to stimulate neuronal activity with light. Above, Channelrhodopsin-2 expressing neurons (green) send long processes from the thalamus to the cortex. Image by Richard Hakim, Adesnik Lab.
Optical tools such as Channelrhodopsin can be used to stimulate neuronal activity with light. Above, Channelrhodopsin-2 expressing neurons (green) send long processes from the thalamus to the cortex. Image by Richard Hakim, Adesnik Lab.

A single neuron or a microcircuit is nearly 1/100 the diameter of a human hair. Therefore the manipulation and monitoring of these miniscule regions requires sophisticated genetic and microscopy techniques.

One such approach is optogenetics: researchers use genetically encoded, light-sensitive proteins that allow them to control neuronal activity by simply illuminating a particular brain cell with light. They then monitor how neighboring cells react to the activation and begin to see how different neural circuits communicate.

The brain is composed of numerous types of neurons, each most likely performing a unique and essential function. Understanding how these different classes of cells interact can provide further information as to how perception is formed at the microcircuit level. To gain this kind of information, Adesnik makes further use of genetically encoded proteins. This time, rather than using ones that activate the neurons, he employs proteins that cause the cells to fluoresce every time they fire. Different fluorophores, compounds that absorb and emit light, can be genetically aimed to label different types of neurons allowing researchers to identify how various types of cells are intricately interacting.

To monitor activity with cellular precision, Adesnik is working to combine optogenetics with holography, or the localization of light in three dimensions. This advanced approach has fostered a relationship with Laura Waller in the Electrical Engineering and Computer Science Department at Berkeley. Waller’s digital holography expertise will allow the Adesnik research team to more precisely control single and multiple cells in both time and space using the previously described genetic tools. By generating and monitoring sophisticated patterns of activity in neural circuits, this collaboration will provide a better understanding of how these circuits are working.

As a new faculty member who has already received many awards, Adesnik has made a strong impression amongst his colleagues at the Helen Wills Neuroscience Institute. From starting with a single cell and working all the way up to entire cluster networks, Adesnik approaches each question from many different angles.

>> Go to the Adesnik Lab website