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.
Neurons in the cortex of a mouse expressing proteins enabling
the 'reading' and 'writing' of electrical activity.
The new technique 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," explained Professor
Michael Hausser of the UCL Wolfson Institute for Biomedical
Research.
"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."
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," said Dr Adam
Packer of the 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."
The paper, Simultaneous all-optical manipulation and recording of neural
circuit activity with cellular resolution in vivo, is published
in Nature Methods.