Prof. Frederic Libersat:  Research Interests 

Neurotoxins and neuromodulation of behavior.

Our first objective is to investigate the neural control of arousal state. The Arousal state appears to be controlled by neuromodulatory systems. To address the issue of arousal at the cellular level, we have initiated a pharmacological study on the neuromodulation of the cockroach’s locomotory circuitries using known insects neuromodulators as well as an insect neurotoxin. The wasp Ampulla compressa subdues its prey by injecting venom apparently directly into the central nervous system. While the vast majority of venomous insects produce paralysis in their prey, A. compressa utilizes a unique biochemical strategy: behavioral modulation.  The inflicted prey animal is rendered unable to organize an escape sequence, but remains ambulatory and is subsequently led by the predator to a suitable oviposition location, where it serves as a nutritional source for the wasp's young.  It is hypothesized that the central nervous system of the prey animal loses its normal ability to activate modulatory circuits involved in behavioral arousal.  The first specific aim of our resarch is to describe the biochemical composition of A. compressa venom, and identify the component(s) - termed here "anti-arousal toxin(s)" (AAT) that are involved in behavioral modulation of prey. This objective is accomplished through a combination of liquid chromatography, mass spectrometry and protein sequencing.  Amino acid sequence information of candidate AATs will be used to construct primers for use in PCR-based amplification of nucleotide sequences for complete characterization of AAT primary molecular structure. Our second aim is to determine the venom’starget in the animal’s CNS. We determine the location of venom injection and which neurons are affected by the venom. By examining the behavior and the physiology of stung animals, we are exploring the mechanism which controls the responsiveness of the neuronal escape circuitry. We also study the effects ofthe neurotoxin on membrane properties of identified neurons and on synaptic transmission between these neurons. Our third aim is to verify the identity of candidate AATs by their introduction into the central nervous system in vivo and in vitro. We will assess their ability to produce the previously described behavioral and physiological properties syndrome caused by the natural stinging sequence.  These include lack of the escape response, characterized by failure of appropriate stimuli to elicit normal escape responses in the prey and selective failure to recruit fast motoneuron circuitry.  Finally, the last specific aim is to determine the precise alterations in synaptic transmission and neuronal membrane properties that underly anti-arousal behavioral modification.  This objective is approached in part through electrophysiological analyses of pre-and postsynaptic responses to appropriate escape stimuli.  Changes in membrane properties are assayed by measurements of membrane resistance, excitability and relevant changes in ion channel properties

Neuronal plasticity

The control of neuronal form has always been a fundamental problem of biological development. Neurons display a wide rangeof dendritic architecture and correspondingly a wide range of firing patterns. It is well established that the maturation of the three-dimensional structure of a neuron during development plays an important role in the appropriate wiring of this neuron with other neurons leading to functional circuits.

To understand specific factors that control the 3-D geometry of a neuron, it would be useful to have access to neurons with a stable 3-D architecture to be used as a template for examining the effect of various experimental manipulations on their geometry and this is rather difficult in most vertebrate systems. Rather, it would be simpler to turn to an invertebrate system, and search for large individually-identified neurons. The identified neuron is a prevalent feature of the invertebrate nervous system; such neurons show a uniform morphology and physiology. One very well studied example of such neurons is the abdominal giant interneurons (GIs) of cockroaches and crickets. The goal of our research is examine questions regarding the rules of dendritic growth and regression by taking advantage of the uniform structure of identified neurons and specific aspects of post-embryonic development of insects. More specifically, we are currently studying the competitive interactions, the representation of a stimulus location and the structural changes associated with aging of dendritic arborizations of identified central neurons. This project will augment our understanding of the basic developmental processes including intrinsic and extrinsic factors that regulate patterned dendritic growth.