Neuroscientists Reveal How the Brain Can Enhance Connections

The human brain is the most complex machine known. Our brain does everything from forming memories to learning new tasks and it does so by encoding the new information and tuning new connections between neurons. These connections are called synapses. Each synapse is characterized by a presynaptic neuron sending chemical signals to one or more postsynaptic receiving cells. In most of the previous studies of how these connections evolve, the focus has been on the role of the postsynaptic neurons. However, in a new research MIT neuroscientists have found that presynaptic neurons also influence connection strength. The details of the study were published in a recent issue of the Journal Neuron.

Troy Littleton, a professor in the departments of Biology and Brain and Cognitive Sciences at MIT, a member of MIT’s Picower Institute for Learning and Memory, and the senior author of the study opined that the mechanism that has been uncovered on the presynaptic side adds to a toolkit that they have for understanding how synapses can change. If it could be understood how synapses change their connections, it would aid scientists better understand neurodevelopmental disorders such as autism, as many of the genetic alterations linked to autism are found in genes that code for synaptic proteins.

The brain has the ability to rewire itself in accordance to changing behavioral condition “ a quality known as plasticity. How it happens is still a mystery but it is an ongoing process that continues throughout life.

In the last 30 years of research, scientists have found that strong input to a postsynaptic cell causes it to traffic more receptors for neurotransmitters to its surface, amplifying the signal it receives from the presynaptic cell. This phenomenon termed as long-term potentiation (LTP), occurs following persistent, high-frequency stimulation of the synapse. Long-term depression (LTD), a weakening of the postsynaptic response caused by very low-frequency stimulation, can occur when these receptors are removed. Littleton added that there has been less focus on the presynaptic neuron’s role in plasticity, partly because it is more difficult to study.

In order to investigate how synapses are strengthened, Littleton along with Richard Cho, a research scientist at the Picower Institute and paper’s lead author, studied a type of synapse called neuromuscular junctions, in fruit flies. The researchers stimulated the presynaptic neurons with a rapid series of action potentials over a short period of time. As expected, these cells released neurotransmitter synchronously with action potentials. However, they were surprised to find that mini events as a result of spontaneous release were greatly enhanced well after the electrical stimulation had ended.

Littleton remarked that every synapse in the brain is releasing these mini events, but people have largely ignored them because they only induce a very small amount of activity in the postsynaptic cell. When strong activity pulses were given to these neurons, these mini events suddenly ramped up and they stayed heightened for several minutes before going down.”

It seems enhancement of minis provoke the postsynaptic neuron to release a signaling factor, still unknown, that goes back to the presynaptic cell and activates an enzyme called PKA. This enzyme interacts with a vesicle protein called complexin, which normally acts as a brake, clamping vesicles to prevent release neurotransmitter until it’s needed. Stimulation by PKA modifies complexin so that it releases its grip on the neurotransmitter vesicles, producing mini events.

When these small packets of neurotransmitter are released at elevated rates, they help stimulate growth of new connections, known as boutons, between the presynaptic and postsynaptic neurons. This makes the postsynaptic neuron even more responsive to any future communication from the presynaptic neuron.

The researchers observed this process throughout the flies’ larval development, which lasts three to five days. However, Littleton and Cho demonstrated that acute changes in synaptic function could also lead to synaptic structural plasticity during development.

Littleton’s lab is now trying to figure out more of the mechanistic details of how complexin controls vesicle release.

References:

https://medicalxpress.com/news/2015-11-neuroscientists-reveal-brain.html

https://news.mit.edu/2015/brain-strengthen-connections-between-neurons-1118