The brain is estimated to contain 100 billion cells that form 100 trillion connections. Brain cells speak to each other by releasing chemicals into a small area known as the synapse, and neighboring cells can listen by using their ability to sense these chemicals. Like our daily conversations, brain cell communication can vary in its effectiveness; all it takes is an inattentive listener or a poor speaker for communication to fail. Understanding synaptic effectiveness is critical, as the strength of brain cell communication is closely related to learning and memory. When we learn something new, brain connections become stronger through a process known as synaptic plasticity, which can involve a clearer speaker (more chemicals) and/or a more attentive listener (greater sensitivity to those chemicals). When brain cell communication fails, memory fails.
Brain cells form their own specialized networks of connectivity, not unlike a large party where multiple conversations occur simultaneously. Some of these connections, or conversations, can be extremely strong and stable while others can be weak and easily disconnected. Not all synapses are the same, and in order to treat brain diseases characterized by weak synapses and poor memories, we first need to understand why some connections are weaker than others, and why certain seemingly strong connections are particularly vulnerable to brain disease. In the present application, we propose a set of experiments that will help understand some of the properties of synapses that contribute to this high degree of variability in connection strength. We will explore synaptic differences first in the healthy brain, and then in the context of Huntington disease, a debilitating neurodegenerative disease characterized by progressive motor and cognitive decline. In all, we expect our research to increase our fundamental understanding of brain cell communication, in both health and disease.