Scientists at UC Berkeley researchers developed a new microscope by combining two-photon fluorescence microscopy and all-optical laser scanning. The microscope can image a two-dimensional slice through the neocortex of the mouse brain up to 3,000 times per second. The team came up with two studies. Also, for the first time, the scientists recorded millisecond electrical pulses between neurons.
The way the individual brain cells cooperate in ensembles of millions is yet to be solved. The brain is like a biological computer, similar to an electronic computer in the sense that it acquires information from the surrounding world, stores it, and processes it in a variety of ways.
The brains of all species are composed primarily of two broad classes of cells: neurons and glial cells. Glial cells perform several critical functions such as structural support, metabolic support, insulation, and guidance of development. Neurons have the property to send signals to specific target cells over long distances.
The first study: pinpoint the firing neuron and follow the signal
The new imaging will help by tracing the tens of thousands of inputs any brain cell receives from other brain cells. Either by exciting or by inhibiting the neuron, the input gradually adds up to the trigger that makes the cell pass the information along to other neurons. When the neuron does that, it looks like it is firing.
The microscope can become a useful resource in becoming a way to figure out the transmission of problems associated with diseases. In the case of a disease, the brain cell becomes inadequate in producing a response to the input. Or, the data is insufficient for a response. Until now, there was no way to observe the process. But now, there is.
The new technique can pinpoint the actual firing neuron and follow the path of the signal, millisecond by millisecond,” said Na Ji, the Lead researcher and a UC Berkeley associate professor of physics and of molecular and cell biology.
The second study: Imaging calcium signaling
Unlike common electrodes, the new microscope can do the imaging for specific types of cells, signaling over much of an entire hemisphere of the mouse brain at once. The result of such an investigation is a 2D image that shows the presence of a particular chemical such as calcium.
It showed slowly changing concentrations of calcium as deep as 350 microns from the brain’s surface, thus offering the further possibility to resolve the synapses of each neuron. Combined with a different technique, Bessel focus scanning the researchers acquired 3D images of the movement of calcium through neurons.
“In brain disorders, including neurodegenerative disease, it’s not just a single neuron or a few neurons that get sick. So, if you want to understand these illnesses, you want to be able to look at as many neurons as possible over different brain regions. With this method, we can get a much more global picture of what is happening in the brain,” said Ji.