Protons have been a proposed neurotransmitter for decades. Yet only recently has solid evidence emerged to support this claim (Du J et al., 2014; Highstein SM et al., 2014). Extracellular protons in the brain are an important signaling messenger involved in neuronal functions. More importantly, numerous neurological diseases such as ischemia, seizure, multiple sclerosis and neurodegenerative diseases all generate acidosis. Understanding how protons signal not only helps us to better understand neuronal physiology but also has important implications in their roles in diseases. Acid-sensing ion channels (ASICs) are proton receptors. Their localization and pH sensitivity put them in an ideal position to sense small pH changes at the synaptic cleft and elsewhere in the neuron. ASICs are important in multiple aspects of peripheral and central neuronal functions. ASICs have been implicated in aspects of behavior and memory including fear-related learning and memory.

 

The long-term goal of my lab is to understand how protons regulate brain circuits and behaviors. Ultimately, this focus will lead to the development of novel therapeutic targets for treating emotional disorders such as anxiety, depression, post-traumatic stress disorder (PTSD) and schizophrenia. We believe that our current and future work will significantly impact the field of neuroscience by addressing the following important questions:

 

1. How do protons function as a neurotransmitter to control synaptic transmission in the brain? Addressing this question in a multidisciplinary fashion will significantly contribute to the understanding of the how neurotransmission occurs and is modified by protons.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

2. How do protons amend and reshape neural circuits? How does this affect subsequent behavior(s)? One of the fundamental questions in neuroscience is how do neural circuits drive and modify behaviors. Illuminating how protons regulate neural circuits will provide insight into this complex and challenging area.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

3. Can protons and their receptors function as a new therapeutic target for the treatment of neurological illnesses? The major proton receptors, ASICs have been suggested as targets for many neuronal diseases, including anxiety, depression, seizure, stroke and Parkinson’s disease, etc.. Developing therapeutics targeting proton signaling may therefore significantly benefit many individuals and improve the quality of life for hundreds of thousands of people.