3D image of a mossy fiber in green contacting the dendrite of Golgi cell in red. The green connections are formed during learning and are critical for the precision of learning. |
Scientists
at the Friedrich Miescher Institute for Biomedical Research (FMI, part
of the Novartis Research Foundation) have discovered neuronal
connections which are formed in the brain when learning occurs, and
which ensure the precision of memory. This work represents an important
step on the path towards an improved understanding of how learning and
memories are stored in the brain. The findings were published today in
the online edition of Nature.
How
are experiences and learning stored in the brain? This “simple”
question has intrigued scientists for several generations. Since the
visionary neuroscientist and Nobel laureate Santiago Ramón y Cajal first
postulated (at the end of the nineteenth century) that structures in
the brain change during learning, and that what is learned – or the
memory of what has been learned – is represented in neuronal
connections, researchers have sought to detect structural changes of
this kind. They have been searching, as it were, for nerve cells which
encode the Pythagorean theorem or the memory of a red dress. So far,
their efforts have not been successful, as the sheer number of neuronal
connections, or synapses, in the brain has proved an insuperable
obstacle.
Neurobiologists
at the FMI have now demonstrated a direct link between the formation of
new synapses in the brain and a learning process, plus the quality of
the associated memory. These findings were reported today in the online
edition of Nature.
A
team led by the group leader Pico Caroni, who is also a professor at
the University of Basel, studied neurons in the hippocampus of mice
learning to navigate a water maze. The hippocampus is a region of the
brain which is essential for learning and recall.
During
learning, the number of synapses onto interneurons was found to double
along hippocampal mossy fibers. These new synapses indirectly inhibited
other cells, known as pyramidal neurons, thereby contributing to the
precision of what was learned. They thus laid down, for example, that at
a certain point in the maze, the mouse should go to the right, but not
to the left, straight ahead, back, up, or down. When the formation of
these synapses was inhibited by the administration of a drug, the mouse
would still find its way, but with less precision – it did not take the
shortest route to the goal.
Caroni
explains: “Our experiments have, for the first time, demonstrated a
clear association between the formation of new synapses and behavior
after learning. So we’ve shown a specific structural change in the brain
induced by learning – and also that this change is required for the
precision of learning.”
The
researchers also found that the newly formed synapses often disappeared
again several days after the end of the learning process. However, even
weeks later, this did not prevent the mice from navigating the maze
successfully, although precision was diminished. “What we’ve
discovered,” says Caroni, “are not structures which are indicative of
memories, but structures which are necessary for precise recall of
what’s been learned. If these mechanisms are disrupted, behavior can be
diverted by more dominant stimuli, which could play an important role in
many memory disorders.”
