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.