Enjoyable Gut Neuroscience

General Aims:

My lab does basic biomedical research investigating how the gastrointestinal tract senses lumenal contents and initiates the correct reflex or motor program. It turns out that the way the gut senses stimuli is similar to how other organs in the body work, like the taste receptors in the tongue or the glomus cells in the carotid body. The main difference is that the gut transfers this information to a complex intrinsic system of nerves present within the wall of the gut. These intrinsic nerves are called the enteric nervous system (ENS) and is recognised as the third division of the autonomic nervous system. It contains about as many neurons as are present in the spinal cord and it has all the components of a reflex arc: sensory neurons, interneurons and motor neurons.

In my lab, we are investingating the role of non-neuronal cells in relaying lumenal sensory stimuli - such as acid, touch or noxious chemicals - to enteric sensory nerve terminals via the graded release of transmitters such as serotonin (5-HT) or ATP. Our methods include electrophysiological recording from single neurons, neuropharmacological analysis of responses in neurons and in the whole organ, modulation of intracellular signal transduction pathways, and electrochemical detection of 5-HT release from nerve terminals. This later technique is currently the focus of the lab's efforts.

Many human disease have a neuronal basis and this can best be studied using animal models. I use the guinea pig intestine as a model for studying complex interactions in a mammalian nervous system and for studying human gastrointestinal function. As a model nervous system, the guinea pig intestine allows us to ask questions such as, how do neurons, receive, integrate and transmit information? Can an isolated mammalian nervous system be understood by analyzing, at the single cell level, the input-output functions of identifiable neurons? As a model of human gastrointestinal function, the guinea pig intestine allows us to ask how the complex interactions between the responses of individual neurons to natural stimuli and the evoked motor reflex relate to normal and disordered function.

Below are some examples of enteric neurons.

• Here is a myenteric neuron with dendrite spines.
• Here is a myenteric neuron positive for nitric oxide synthase.
• Here are some nice pictures of myenteric neurons containing the calcium binding protein calretinin.
• Here is a myenteric AH neuron that is sensitive to lumenal chemicals.