A recent study has overturned a long-held belief in neuroscience,demonstrating that the brain employs different transmission sites to achieve various forms of plasticity,rather than a single shared site.

The findings,published in Science Advances, provide a more in-depth understanding of how the brain balances stability and flexibility, a crucial process for learning, memory, and overall mental well-being.

“Our findings reveal a key organizational strategy in the brain.”

Neurons communicate via synaptic transmission, a process where a neuron releases neurotransmitters from a presynaptic terminal. These neurotransmitters then travel across the synaptic cleft and bind to receptors on a neighboring postsynaptic neuron, initiating a response.

Historically, scientists have thought that spontaneous transmissions (random signals) and evoked transmissions (signals triggered by sensory input) originated from a single canonical synaptic site, relying on shared molecular machinery.

Though, using a mouse model, the research team, led by Oliver Schlüter, associate professor of neuroscience at the University of Pittsburgh, discovered that the brain utilizes separate synaptic transmission sites to regulate these two types of activity. Each site has its own developmental timeline and regulatory rules.

“We focused on the primary visual cortex,where cortical visual processing begins,” says Yue Yang, a research associate in the neuroscience department and first author of the study.

“We expected spontaneous and evoked transmissions to follow a similar developmental trajectory, but instead, we found that they diverged after eye opening.”

As the brain began to receive visual input, evoked transmissions continued to strengthen. Conversely, spontaneous transmissions plateaued, suggesting that the brain uses different forms of control for the two signaling modes.

To investigate this further, the researchers used a chemical to activate previously silent receptors on the postsynaptic side. This led to an increase in spontaneous activity, while evoked signals remained unchanged, providing strong evidence that the two types of transmission function through distinct synaptic sites.

This separation likely allows the brain to maintain consistent background activity through spontaneous signaling, while simultaneously refining behaviorally relevant pathways through evoked activity. This dual system supports both homeostasis and Hebbian plasticity, the experiance-dependent process that strengthens neural connections during learning.

“Our findings reveal a key organizational strategy in the brain,” says Yang. “By separating these two signaling modes, the brain can remain stable while still being flexible enough to adapt and learn.”

The implications of this research are far-reaching. Abnormalities in synaptic signaling have been linked to conditions such as autism, Alzheimer’s disease, and substance use disorders. A deeper understanding of how these systems function in a healthy brain could help researchers identify how they become disrupted in disease.

“Learning how the brain normally separates and regulates different types of signals brings us closer to understanding what might be going wrong in neurological and psychiatric conditions,” Yang says.