Clark A Lindgren

In my laboratory, we study the chemical synapse, a specialized connection where neurons communicate with neighboring cells such as sensory receptors, muscle cells, or other neurons. Our primary goal is to unravel the mechanisms through which the presynaptic cell regulates the release of its messenger molecule, known as the neurotransmitter, and how this process can be influenced by synaptic activity. Recently, our research has been centered on exploring synaptic homeostasis, a fundamental process that synapses employ to maintain stability in response to various physiological and sometimes pathological changes.

One intriguing example of synaptic homeostasis that plays a critical role in the function of the synapse between a motor nerve and muscle is referred to as presynaptic homeostatic potentiation (PHP). This phenomenon becomes evident when certain neurotransmitter receptors on the muscle are blocked, prompting the nerve to increase neurotransmitter release to restore normal muscle function. Despite being aware of PHP for more than four decades, the exact messenger that communicates the synaptic deficit back to the nerve has remained elusive. However, our recent investigations suggest that hydrogen ions (protons) could serve as the potential mediator. We have observed that PHP is hindered by the specific inhibition of acid-sensing ion channels, which are activated by an increase in hydrogen ion concentration. Moreover, our studies demonstrate that strong pH buffers, which prevent fluctuations in hydrogen ion concentration, also impede PHP. Currently, we are devising methodologies to measure the pH in the synaptic cleft, the minuscule space separating the nerve and muscle at the synapse, to further elucidate and characterize the role of hydrogen ions in PHP. Additionally, we are delving into the underlying reasons why a partial blockade of neurotransmitter receptors leads to an elevation in hydrogen ion concentration in the synaptic cleft.

In addition to supervising student research in my lab, I teach a diverse array of courses encompassing neuroscience, physiology, and cell biology. This includes my involvement in a section of our innovative introductory biology course, Bio 150: Introduction to Biological Inquiry. In my particular Bio 150 course, students engage in designing and conducting experiments aimed at unraveling the mysteries of synaptic transmission using a neuromuscular preparation derived from the tail of the crayfish.