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Perception, Learning and Memory

Perception, Learning and Memory

, learning and

he is a highly remain the focus of learning and memory change. Proteins are continually recycled complex organ shaped by hun- research. Changes in neuronal activity and and replaced, and new proteins are re- dreds of millions of years of ev- synaptic strength are to underpin quired for learning and memory to occur2. olution. It has evolved to detect learning and memory. Moreover, neuronal So, how can some remain stable meaningful patterns, to learn, loss and synaptic malfunctioning have when so many of the underlying compo- memorizeT and them, and to adapt. been implicated in various neurological dis- nents are constantly changing? Our neural networks can produce and de- orders that involve learning and memory code signals, extract and deficits. mapping the Brain process useful features from the environ- ment, and produce vital innate behaviours Unravelling perception, The study of perception, learning and mem- such as eating, fleeing and mating. learning and memory ory offers many challenges and research op- Amazingly, this specialized structure self- portunities. Our technical toolbox means assembles, growing from one cell to tens Despite intense efforts to understand it is now possible to catalogue and describe of billions, and each developing brain in- perception, learning and memory, there the constituents of the brain and its neural corporates both hidden biases shaped are still huge gaps in our . circuits — an essential step towards under- through natural selection, and the means We have yet to pinpoint the neuronal standing the brain. All that is needed is the with which to sculpt itself throughout its mechanisms that underlie perception. time and optimized methods to help han- lifetime as the individual encounters new Millions of in structurally diverse dle huge data sets. experiences and sensations. networks activate for us to perceive even The development of high-resolution the simplest of objects, and teasing apart serial electron microscopy, super-resolution 3,4 Brain Basics the neural circuits that are responsible is light microscopy and multicoloured no small achievement. genetic tools for neuronal labelling5, and Our brain contains billions of neurons, Perception and memory are intimate- the increased affordability of immense which are specialized cells that process and ly interlinked — perceiving an object computing power, make it possible to im- transfer information, and are arranged into would be meaningless without the ability agine a day when the connection matrix of complex cellular circuits. These cells com- to recall and link it to corresponding a small-to-medium-sized brain (perhaps municate via synapses, which are junctions memories. Although perception, memory that of a fly or a mouse) will be known with that allow the transfer of chemical or elec- formation and recall are likely to rely on a reasonable degree of accuracy. This en- trical information from one to the interlinked mechanisms and substrates, deavour requires the ability to handle enor- next (Fig. 1). we have yet to understand them fully, or mous data sets, and a multi-disciplinary Neurons are the most diverse cell type in to decipher the effects of sleep, approach incorporating molecular biology, the body. They are usually polarized with and other ill-understood processes on genetics, electrophysiology, imaging, elec- specialized projections for receiving (den- learning and memory. tronics, nanotechnology, mathematics, drites) and relaying (axons) information We do know that memory is a spatial- computer science and nonlinear dynamics. (Fig. 2). Sensory neurons convert external ly and temporally dynamic process. As It will breed a new type of cooperation stimuli, such as light, sound or pressure, into memories are stored and consolidated, between areas of science that have often electrical signals, whereas motor neurons they are shifted from one part of the brain worked separately. use electrical signals to control muscles. A to another in a process that can take weeks third, more abundant, type of neuron lie and appears to be dependent on brain neUral networking between these inputs and outputs. activity during certain phases of sleep1. Non-neuronal cells, called glia, Memory-related proteins, synapses, neu- A major challenge for modern fundamental roles in the development, rons and neural networks are also dynam- is to explain perception and behaviour support and plasticity of neural circuits; ic. Neurons die off as part of normal in terms of neural activity. Given the size however, neurons and their synapses ageing, yet for the most part we notice no of the brain, the number of neurons and

he dynamic and coordinated behaviour of neurons in the brain that when memory-related neurons in the brain fire synchronously can be detected in brain oscillations that occur at a variety with brain waves at the theta frequency (2–8 hz) during learning, the T of frequencies (for example, 2–200 hz). a recent study by resulting memories are stronger than if this synchronization does not researchers at the max planck institute for Brain research found occur (Rutishauser, U. et al., Nature 464, 903–907, 2010).

20 Research Perspectives of the Max Planck Society | 2010+ Biology and Medicine

perception, learning and memory are interconnected processes controlled by the coordinated activity of molecules, synapses, cells and neural networks within the brain.

although we know much about the activity of individual neurons and synapses, we know far less about how these components interact.

neuroscience techniques must evolve to realize a new era of multidisciplinary research studying networks of interacting elements.

Fig. 1 | Neuron Fig. 2 | Neuron structure communication

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). The intricate, branching dendrites Neurons (labelled here with a pink Much is known of the functioning of of a cultured neuron can be fluorescent-tagged marker protein) visualized by labelling them with the communicate with each other individual neurons and synapses, but fluorescent-tagged marker protein via specialized junctions called much less about their coordinated action microtubule-associated protein 2 synapses (labelled here with a green in ensembles of millions. The brain derives (MAP2). fluorescent-tagged marker protein). its magic from coordinated activity on the large scale and high degrees of specializa- tion on the small scale7. Networks, neurons and molecular con- Much is known of the functioning of individual stituents need to be studied in combina- 13, 897 - 905 (2010). tion rather than in isolation, and experi- neurons and synapses, but much less about their mental techniques traditionally used to » coordinated action in ensembles of millions. study individual elements need to evolve towards this. One new approach involves light-activated genetic switches that Nature Neuroscience control the activity of specific, discrete Fig. 3 | Levels of neuronal populations8,9. This technique — ‘optogenetics’ — is already bearing fruit and it is thought that such studies will help reveal cell within the con- text of neural circuits. Neural activity needs to be sampled at an intermediate scale: that of networks of interacting elements. Rather than study- ing a handful of cells in a handful of , studies should focus on the pop- ulation level, with high-sampling density and mobile animals. This will be techni- cally 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 Magnetic-resonance images can currently resolve certain brain structures, whereas the contributory mechanisms might offer implanted electrodes (arrows) are needed to reveal the electrical activity of 10 us the chance to influence and improve individual neurons .

Top right Images: courtesy of the Schuman laboratory. Reprinted with permission from Macmillan Publishers Ltd: these most human of skills.

➟ For references see pages 38 and 39 2010+ | Research Perspectives of the Max Planck Society 21