Brain cells stay in focus as rats roam

Besides receiving incoming signals from other brain cells, a neuron’s branchlike dendrites somehow participate in computations that the cell makes to decide whether it should fire or not.

A new type of microscope may illuminate the murky details of that process and other neuronal functions by enabling researchers to peer into the brains of active laboratory rats, says Michale S. Fee of Lucent Technologies’ Bell Laboratories in Murray Hill, N.J.

Currently, scientists must immobilize and anesthetize rats to inject dyes into single neurons and observe subcellular activity through a hole in the skull. Certain dye molecules fluoresce under laser light if they have bonded with calcium ions flowing into cell regions that are transmitting an electric pulse. Brain researchers already can observe those glowing molecules in subdued animals through large, stationary microscopes.

However, Fee, David W. Tank, now of Princeton University, and Fritjof Helmchen and Winfried Denk of the Max-Planck Institute for Medical Research in Heidelberg, Germany, thought they could learn more by studying brain function during a rat’s normal activity.

In the Sept. 27 Neuron, they describe a new tool for this purpose: a featherweight fluorescence microscope that mounts over a hole in an active rat’s skull. The instrument’s laser, controlling computer, and display are attached to the microscope via a tether of optical fibers and wires.

Despite a few bugs still to be worked out, the researchers expect the apparatus to allow animals to pursue most of their ordinary behaviors, even as it images specific neurons in action.

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