11.09.2015

Molecular 'tuning' of cortical interneuron properties

Computers are often used as a metaphor for the brain, with logic boards and microprocessors representing neural circuits and neurons, respectively. While this analogy has served neuroscience well in the past, it is far from correct. The brain is a highly dynamic, self-organising system, in which internal and external influences continuously shape information processing “hardware” by mechanisms not yet understood, and in a way not achieved by computers.

Researchers from the MRC CDN, led by Professor Oscar Marín, have just shed light into this problem. They have discovered that some neurons in the cerebral cortex can adapt their properties in response to changes in network activity such as those observed during learning of a motor task, for example. The authors studied two apparently different classes of fast-spiking interneurons, only to discover that they were actually looking at the same piece of “hardware” which had the ability to oscillate between two different ground states. The authors also identified the molecular factor responsible for tuning the properties of these cells, a transcription factor – a protein able to influence gene expression – known as Er81.

Fast-spiking interneurons are part of a general class of neurons whose primary role is regulating the activity of the principal cells of the cerebral cortex, known as pyramidal cells. The cerebral cortex is outer layer of the brain and is associated with cognition, language and memory.

“Our findings provide a mechanistic explanation for the activity-dependent regulation of interneuron properties”, said Nathalie Dehorter first author of the study. “The results of this study support the notion that activity play a prominent role in the specification of neuronal properties, which adapt in response to internal and external influences to encode information.” In other words, that our “hardware” is tuneable, at least to some extent.

Understanding the dynamic mechanisms that lead to the emergence of brain functions through the development and continuous remodelling of neural circuits, and the constraints that disease and ageing impose to this multi-modal plasticity has important implications that go beyond fundamental neuroscience, from education policies to brain repair.

Dehorter N, Ciceri G, Bartolini G, Lim L, del Pino I, Marín O (2015) Tuning of fast-spiking interneuron properties by an activity-dependent transcriptional switch. Science 349: 1216-1220.

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