Learning programs the brain. It is nature’s way to create
simultaneously both “hardware” and “software” for the brain. Neuroscientists
have long known that learning experiences change the functional circuitry that
is used to process and remember a given learning event. The circuit change is
anatomical: electron microscope photographs reveal that the synaptic changes take
the form of little blebs located on dendrites. These blebs are called
“dendritic spines,” and their size and number change in response to learning
and memory formation. You might think of the induced change as a physical
location for information storage. What is stored at any given spine is an
increase in the probability that the spine will participate in activations that
generate recall of the stored memory from all the spines that were enhanced in
creating the memory.
Functionally, the change operates as a template that resides more
or less permanently that is available not only to recall the original learning event
but to respond to similar events in the future. Of course, no one synapse
accounts for these recall and programming effects. However, the learning and
memory results from the collective enhancement of all the enhanced dendritic
spines in the participating circuitry. The templates thus created provide a way
for the brain to program itself for future capabilities. Learning how to solve
one kind of task makes it easier to learn new tasks that are similar. This is
the basis for the so-called “learning-set,” a concept introduced many decades
ago by Harry Harlow.
We tend to think about such matters in the education of
children. However, the principle applies at all ages, including seniors. The
aging brain responds to learning the same way a child’s brain does: it grows
new task-specific synapses that can be recruited for other uses.
The learning effect is manifest in the growth of existing
synapses and the formation of new synapses. In the absence of mental
stimulation, the spines degenerate. Indeed, a typical effect of aging is that the
brain actually shrinks as a consequence of the cumulative shrinkage of spines. Many
neurological diseases are characterized by reduced synaptic density:
schizophrenia, autism, and dementia. An opposite problem occurs with drug
addiction, where certain synaptic connections are strengthened by the drug,
essentially creating a way to store a memory for the addiction.
Until now, we have not learned as much about the chemical
changes that occur with learning. A recent study from Thomas Jefferson
University reveals that new patterns of molecular organization develop as
connections between neurons strengthen during learning. The researchers
basically asked the question, “What does learning look like at the molecular
level? Using super-resolution live-cell microscopy, the researchers confirmed
the enlargement of synapses previously reported by others. But they also saw
that that during a learning experience the molecules involved in sending and
receiving the signals between neurons appeared to be organized in clumps or
"nanomodules" that both dance and multiply when stimulated by
learning-like signals.
The researchers developed a novel technique wherein they could
visualize the chemical involved in transmitting signal from one neuron to
another. Chemicals on the pre-synaptic side appeared green and those on the
receiving postsynaptic sign appeared as red. Then while observing the colors,
they observed live neurons in real time as they sent signals to each other via
their neurotransmitter chemical systems. The color changes indicated that
during signaling activity, the presynaptic chemicals clumped together and bound
to clumped molecules on the postsynaptic side. The clumps appeared to have a
uniform size. When the presynaptic neurons were stimulated in a way that
promoted spine enlargement, they saw that the number of chemical clumps
increased. Such stimulation caused non-moving clump to jiggle and move around the
synaptic spine, with pre- and post-synaptic chemicals moving in lock-step.
Maybe this jiggling helps to trigger the biochemical cascade that
neurotransmission causes to change activity in the post-synaptic neuron.
Perhaps we don’t think enough about the movement of molecules in
living tissue. All chemicals in solution bounce around randomly. Clumping
together and jiggling in lock-step creates new ways for chemicals to produce
their effects. Apparently, the clumping is the triggering event for the enlargement
of dendritic spines that creates a structural basis for memory.
This kind of chemical interaction is not only relevant to
learning. It also applies in unknown ways to the altered function in addictions
and other neurological diseases in which strong interneuronal connections
become too strong. Research on neurotransmitter clumping in disease states has
not yet begun, but here we may find clues on how to treat some of these
conditions. Clearly, disrupting the clumping would disrupt the ability to
strengthen synapses. While we want our synapses strengthened to promote normal
learning, we don’t want this to happen for example, for opiate pain relievers, which
create addiction. At the molecular level, addiction is a learned condition.
Sources
Hruska, M. et al.,
"Synaptic nanomodules underlie the organization and plasticity of spine
synapses," Nature Neuroscience,
DOI: 10.1038/s41593-018-0138-9, 2018.
