A major challenge for modern neuroscience is to explain perception and behaviour in terms of neural activity. Given the size of the brain, the number of neurons and the distributed nature of neural activity6, it is increasingly clear that traditional methods will yield limited results. Patch clamping, for example, can record the activity of single cells at high resolution, but tells us nothing of how these cells contribute to larger circuits. Functional magnetic-resonance imaging offers a broad view of brain activity on a large scale, but lacks the resolution to reveal the activity of individual neurons (Fig. 3).
Much is known of the functioning of individual neurons and synapses, but much less about their coordinated action in ensembles of millions. The brain derives its magic from coordinated activity on the large scale and high degrees of specialization on the small scale7.
>> Much is known of the functioning of individual neurons and synapses, but much less about their coordinated action in ensembles of millions.
Networks, neurons and molecular constituents need to be studied in combination rather than in isolation, and experimental techniques traditionally used to study individual elements need to evolve towards this. One new approach involves light-activated genetic switches that control the activity of specific, discrete neuronal populations8,9. This technique — ‘optogenetics’ — is already bearing fruit and it is thought that such studies will help reveal cell function within the context of neural circuits.
Neural activity needs to be sampled at an intermediate scale: that of networks of interacting elements. Rather than studying a handful of cells in a handful of animals, studies should focus on the population level, with high-sampling density and mobile animals. This will be technically challenging, and will rely on major developments in the fields of optics, microelectronics, nanoelectronics and computer science.
The rewards will be great. Deciphering the neural basis of perception, learning and memory is a fundamental part of understanding how the brain functions in health, ageing and disease. Teasing apart the contributory mechanisms might offer us the chance to influence and improve these most human of skills.
The dynamic and coordinated behaviour of neurons in the brain can be detected in brain oscillations that occur at a variety of frequencies (for example, 2–200 Hz). a recent study by researchers at the Max Planck Institute for Brain research found that when memory-related neurons in the brain fire synchronously with brain waves at the theta frequency (2–8 Hz) during learning, the resulting memories are stronger than if this synchronization does not occur (Rutishauser, U. et al., Nature 464, 903–907, 2010).