Integrative Neurobiology

Our laboratory works on the neural basis of behavior in the sea hare, Aplysia. The behavior of this animal is relatively slow, and its control is much simpler than is that of mammals. The nervous system also contains many large neurons that are readily identified as unique individuals. Identifying neurons and their interconnections allows one to determine how cellular and network properties of neurons give rise to behavior. Most of our work focuses on the control of feeding behavior. We have identified a number of key neurons that are part of a central pattern generator controlling and organizing repetitive feeding responses. The decision of whether or not to respond to a food, or to change from one phase of a feeding behavior to another, is made by these neurons. We are examining the biophysical properties of these neurons, to understand how these properties give rise to the ability of the neurons to decide. The neurons are examined using current and voltage clamp recordings, in isolated ganglia as well as in cell culture. Computational methods are also used to reconstruct neurons and networks from the recorded data.

Aplysia feeding can be modulated by changes in motivational state and by learning and memory. We are actively examining the cellular mechanisms underlying modulation of feeding. We have identified a feeding state in which constant access to food inhibits feeding. Experiments are now identifying the environmental stimuli controlling this state. The neural sites at which these stimuli act to modulate feeding are also being examined.

We are also examining the mechanisms underlying a learning paradigm in which Aplysia learn that a specific food is edible or inedible. We have found that long-term memory after training is dependent on three contingent events during the training. One of the three contingent events, efforts to swallow, is signaled by the release of two transmitters, histamine and NO. Exogenous application of these transmitters replaces efforts to swallow during training. Recent work has examined some of the earliest molecular events following training that lead to subsequent long-term memory. We have found that training induces the expression of the transcription factor C/EBP. Surprisingly, C/EBP mRNA, and protein were expressed exclusively in the buccal ganglia after training. These ganglia have primarily a motor function, an unusual site to localize taste-specific learning.

We have recently uncovered a new mechanism by which the unconventional neurotransmitter NO regulates behavior. NO is released continuously by a number of key regulatory neurons. The background release of NO inhibits feeding.

Techniques used in the laboratory include observations of behavior in the intact animal, pharmacological and surgical treatments aimed at changing behavior, chronic extracellular recordings from freely-behaving animals, acute extracellular and intracellular recordings and voltage clamping from neurons in situ in isolated ganglia, cell culture of neurons and subsequent intracellular current and voltage clamping, real-time PCR analysis of mRNA, and computer simulations of neurons and neural networks.