Mapping connections in the brain to understand visual processing

Scientists at the Medical Research Council's National Institute for Medical Research (NIMR; now part of the Francis Crick Institute) have, for the first time, combined neuroanatomy, physiology and genetics to describe the structure and function of a specific circuit of brain cells involved in processing visual information.

They next plan to use the method to map brain cell, or neuron, connections in mouse models of Down Syndrome and autism, hoping to shed light on these common disorders.

Dr Troy Margrie of NIMR and University College London explained: "The processing of external information in the world around us is a fundamental brain function that is required for almost all human behaviours.

"The outermost structure of the mammalian brain - the neocortex - evolved, at least in part, to integrate information from our different senses, and contains many types of neurons. Its connectivity has been the focus of investigation for more than a century. This information, together with data about the electrical properties of neocortical cells, presents a very complex picture of how these cells function."

Mateo Vélez-Fort and his colleagues in Dr Margrie's lab directly investigated the relationship between the morphology, connectivity and functional response properties of two types of cell in a part of the primary visual cortex of the mouse (the part of the brain that processes sight information). They recorded electrical activity of individual neurons while simultaneously delivering a DNA virus to recorded cells that infected upstream neurons - allowing these connections to be traced. A type of imaging was then used to map the connections through the whole brain.

The researchers discovered that one of the cell types, called cortico-cortico cells, received most of their input from local visual areas. In contrast, cortico-thalamic cells (so-called because their nerve fibres run towards another part of the brain called the thalamus), received long-range connections from parts of the cortex involved in higher-order visual and spatial processing.

Together the data show sensory processing in this part of the brain relies on targeted long-range connections to specific cells.

Dr Margrie concluded: "Until very recently neuroanatomists, physiologists and geneticists have been unable to combine their respective toolkits to interrogate the relationship between cortical connectivity and function at the level of individual cells.

"This is now recognised as an essential step, since each method in isolation is unable to directly investigate this issue at the level of a single cell. This is particularly important in areas of the brain where functionally diverse populations of cells come together to form networks where specific connections are unknown.

"By using this method we have provided the first description of the function and connectivity of a specific circuit in the neocortex. After first mapping the connectivity and function of these cells in the primary sensory areas of normal mice, we will assess the connections in genetic models of Downs Syndrome and autism."

The paper, The Stimulus Selectivity and Connectivity of Layer Six Principal Cells Reveals Cortical Microcircuits Underlying Visual Processing, is published in Neuron.

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