University College London. UK: UCL researchers have developed an innovative way to understand how the brain works by using flashes of light, allowing them to both ‘read’ and ‘write’ brain signals.
The new technique, described in Nature Methods, combines two
cutting-edge technologies for reading and writing electrical activity in the
brain. First, genetically encoded activity sensors enable neuroscientists to
engineer nerve cells to visibly light up when they are active. Expressing
light-sensitive proteins in the same nerve cells then allows these cells to be
activated with flashes of light. By combining these two techniques, the team
was able to both observe and control brain activity in mice.
“Combining reading and writing of activity in the same neurons in
the intact brain could revolutionize how neuroscientists can interact with and
understand brain activity,” explains Professor Michael Hausser (UCL
Wolfson Institute for Biomedical Research), senior author of the study. “One of
the best things about having an extended conversation with someone is that you
can really get to know them. With time, their responses can give you a feel for
the key questions to ask in order to understand their character. Just as we
combine specific words into sentences that elicit a reply from someone we talk
to, we used light to activate specific combinations of nerve cells in the
intact brain and record how the other cells respond. In this way, we hope to be
able to ask the brain questions and, from its answers, better understand how it
works.”
We are very excited to use this technology to probe the basis of how groups
of neurons and ultimately the brain stores and processes information from the
world around us
To activate multiple brain cells simultaneously, the researchers
split up the incoming beam of light using a holographic technique to direct
smaller beamlets to individual cells of their choosing. The team selected a
group of neurons in the cortex that are specifically responsive to the
sensation of touch, reliably activating them while recording the flashes of
activity in both the activated neurons and in hundreds of neighbouring neurons.
This allowed them to “interrogate” the circuit in a precise way, activating
selected brain cells in different patterns and measuring how the circuit
responds. These experiments could be repeated in the same sets of neurons in the
same animals over days and even weeks, allowing an extended ‘conversation’ with
the circuit. In future, they hope that by replacing a physical stimulus with
precise, holographically controlled brain activity the ‘neural code’ of sensory
perception can be cracked, with far-reaching medical and scientific
consequences.
“We are very excited to use this technology to probe the basis of
how groups of neurons and ultimately the brain stores and processes information
from the world around us,” says first author Dr Adam Packer (UCL
Wolfson Institute for Biomedical Research). “This work provides a new way for
neuroscientists to have a long-term and engaging conversation with the cerebral
cortex in the brain of a mouse. Crucially, since the methods of both recording
and activation rely on light, this technique is flexible and non-invasive.”
The nature of the ‘conversation’ depends only on where and when the
researchers choose to point the light. Insights gained using this approach will
be useful not only for understanding the ‘neural code’, but also for
understanding how neural activity goes awry in neurological conditions such as
autism and dementia.
Dr John Isaac, Head of Neuroscience and Mental Health at the
Wellcome Trust said: “This impressive research shows how electrical signals
sent by individual neurons in the brain can be ‘read’ and ‘written’ using an
exciting combination of emerging technologies. This new approach helps us
understand how complex behaviour is produced by the nervous system. The work is
a step towards realising one of the ultimate challenges of modern science:
understanding how the brain processes information to produce appropriate
actions.”
Funding for this study was provided by the Wellcome Trust, the
Gatsby Charitable Foundation, the European Commission, the European Molecular
Biology Organization, the Medical Research Council and the European Research
Council.