A miniature head-mounted microscope, designed for use on rats, could monitor activity in individual brain cells, says the US team that developed it. The technological breakthrough should, for example, give scientists an unprecedented insight into how memories are formed.
鈥淭he only real alternative to our microscope for 鈥榳atching鈥� brain activity at present is to use electrical recordings,鈥� says Winfried Denk of Bell Laboratories in New Jersey.
Michael Hauser, an expert on brain cell communication at University College London, says: 鈥淭his is a real breakthrough. It will allow us to look at concentration changes of various signalling molecules in the intact brain.鈥�
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Brain cells communicate when electrical pulses 鈥� called action potentials 鈥� 鈥渇ire鈥� the release of chemical neurotransmitters. These neurotransmitters cross the gaps between brain cells and can trigger further action potentials in neighbouring cells.
Incoming signals cause changes in the concentration of calcium in the receiving cell 鈥� and the extent of these changes determines whether or not the signal will be passed on.
By using the microscope and a fluorescent dye to measure calcium concentrations in receiving cells, scientists can investigate the complex pattern of biochemical changes that dictate whether or not the cell will fire.
All you see by watching electrical activity is action potentials, says Denk. 鈥淵ou cannot study the process in the cell by which it makes a 鈥榙ecision鈥� whether to fire an action potential or not.鈥�
Freedom of movement
Five years ago, Denk鈥檚 team created a version of the microscope for use on immobilised, anaesthetised animals. But to study brain activity during normal behaviour, it is essential that the animal is free to move, he says.
The microscope, which is surgically attached to a rat鈥檚 skull, is 7.5 centimetres long and weighs 25 grams. 鈥淎ll we have really done so far is to demonstrate the feasibility of the microscope 鈥� we haven鈥檛 shown that the rats behave normally while wearing it,鈥� Denk says. 鈥淏ut they do seem to act reasonably normally.鈥�
The team鈥檚 microscope uses an optical fibre to obtain images. 鈥淲e have resolution in the micrometre range and we can look at what is happening in a small part of a neuron,鈥� Denk says.
The microscope can view only 200 micrometres below the surface of the cortex. But this should be enough to provide valuable data, says Denk: 鈥淥ne always wants to go deeper 鈥� but there is a lot of circuitry at this depth, a lot of connections between axons and dendrites.鈥�
Initial tests of the microscope suggest that only severe head movements blur the image, and Denk鈥檚 team hopes scientists will soon be able to use it to probe cortical activity in incredible detail.
鈥淚n the immediate future, we will be able to study the question of attention and motor planning,鈥� he says. 鈥淎nd if you study the cortex, you study memory. At the moment, no one really knows for sure where and how memories are stored 鈥� so the microscope will also be useful for studying this.鈥�
Journal reference: Neuron (vol 31, p 903)