John WalrondBiomedical Sciences
235 Physiologyjohn.email@example.com (970) 491-5588
Studies of synaptic transmission at the neuromuscular synapse have made important contributions to understanding synaptic structure and function. However, this synapse is highly specialized to ensure that each action potential in the motor neuron releases sufficient neurotransmitter to elicit an action potential in the postsynaptic muscle fiber. Such a one-to-one relationship is unusual for synapses in the central nervous system where action potential generation in the postsynaptic neuron results from the integration of many small potentials produced by numerous synaptic inputs. Regulating the output of neurons in the central nervous system depends largely on setting the "gain" of the pre- and postsynaptic cells either by altering the amount of neurotransmitter released presynaptically or by affecting the amplitude of the postsynaptic potential. Nicotinic acetylcholine receptors in the brain appear to be involved in this process. The brain contains numerous nicotinic acetylcholine receptor subtypes which are categorized according to the a and b subunits that they contain. The alpha subunits in the central nervous system include those numbered a2-9, although a8 has not been found in mammals. There are two beta subunits. Neurodegenerative diseases, including Alzheimer's disease and Parkinsonism, are associated with the loss of cholinergic neurons in the central nervous system. In addition, the relationships between nicotinic acetylcholine receptor function and addictive behaviors, particularly tobacco consumption, have important implications for public health policies. Despite the importance of these receptors in normal and diseased nervous systems, little is known about their distribution and function at the cellular level. Electrophysiological, pharmacological, immunohistochemical, and ultrastructural techniques are used in my laboratory to study nictonic acetylcholine receptors in the central and peripheral nervous systems. Electrophysiological and pharmacological studies in my lab have shown that alkaloids isolated from Delphinium spp. including methyllycaconitine (MLA), nudicauline, 14-deacetylnudicauline (14-DN), barbinine and deltaline specifically block nicotinic acetylcholine receptors in the brain and at neuromuscular junctions.