What is thought? How do we remember things? Although neurobiologists have made great progress in understanding elementary brain function, fundamental questions about brain function still elude us. The mechanisms involved in learning and memory are somehow encoded in the communication between the millions of nerve cells in our brain. In addition, over 400 million people suffer worldwide from some form of neurological or psychiatric disorder such as depression, bipolar disorder, schizophrenia and epilepsy. These complex illnesses somehow disturb the delicate balance of brain function not by dysfunction in one particular protein, but rather by somehow upsetting the activity of neural networks.

The research in our laboratory uses primarily electrophysiological techniques combined with molecular biology to probe electrical signals in individual nerve cells and in small neural networks. Primarily, we are interested in how the N-methyl-D-aspartate (NMDA) ion channel works and also want to test its involvement in neural network function and synaptic integration.

NMDA receptors are found in the postsynaptic membrane of excitatory synapses (excitatory connections between nerve cells). They are activated by the neurotransmitter, glutamate, and are responsible for converting the chemical signal of synaptic glutamate release by the presynaptic neuron, back into an electrical signal in the postsynaptic neuron. These channels are permeable to monovalent cations and calcium. Calcium influx initiates many intracellular cascades and thus the NMDA receptor has been implicated in many physiological processes like learning and memory. These channels are also involved in pathological processes like global cerebral ischemia and may be involved in schizophrenia and neurodegenerative diseases like Huntington’s and Parkinson’s disease.

In a separate avenue of investigation, we are elucidating the specificity and mode of action of scorpion toxins on voltage gated sodium channels. Scorpion toxins are highly selective. Although these scorpion toxins are only 65 amino acids long, they can differentiate between mammals and insects as well as between sodium channels in different tissues such as the brain, heart or muscle. We have been able to tailor the action and specificity of these toxins in the hope that one day, they may serve therapeutically on very specific drug targets within the body. Such therapeutic uses may be important in producing new anesthetics or in alleviating chronic pain.