Vincent A. Chiappinelli, Ph.D. The Ralph E. Loewy Professor Chair, Dept. of Pharmacology & Physiology Tel: 202-994-3541

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Presentation transcript:

Vincent A. Chiappinelli, Ph.D. The Ralph E. Loewy Professor Chair, Dept. of Pharmacology & Physiology Tel:

Principal Investigator: Vince Chiappinelli Co-Principal Investigator: Jian-Zhong Guo Co-Principal Investigator: Eva Sorenson Consultant: David Perry Consultant: Michael McIntosh (Univ. Utah) FUNCTIONAL PROPERTIES OF NEURONAL NICOTINIC RECEPTORS NIH Competitive Renewal – 21 st Year Starts Dec 2006 MAIN GOAL: Combine electrophysiological and morphological methods to determine roles of nicotinic receptors (nAChRs) in synaptic transmission in the CNS during development

Patch-Clamp Recording from Visualized Nerve Cells in Living Brain Slices Allows Real-Time Recording of Synaptic Responses

Electrical Stimulation of Cholinergic Fiber Tract: Postsynaptic nicotinic response in SPL neuron In Presence of GABA and Glutamate ELECTRICAL STIMULATION OF CHOLINERGIC INPUTS HERE TO RELEASE ACETYLCHOLINE, THE ENDOGENOUS TRANSMITTER THAT ACTIVATES NICOTINIC RECEPTORS Nicotinic Receptor Antagonist DH  E Blocks Excitatory Effect of Released Acetylcholine

ACh increases evoked glutamatergic currents by 3-fold through activation of presynaptic nicotinic receptors Ventral Lateral Geniculate Neuron (LGNv)

Schematic diagram of selected circuitry within the ventral Lateral Geniculate Nucleus (LGNv) Locations of nicotinic receptors are indicated by asterisks. Pharmacological tools allow identification of subtypes of nAChRs.  4*  6*  7*  *

A: Autoradiography of  6* nicotinic receptors B and C: Confocal Microscopy showing Co-Localization of Synaptotagmin and  7 nicotinic receptor subunit   -Conotoxin MII autoradiography in rat brain: LGN and optic tract heavily labeled revealing  6* receptor locations Synaptotagmin (a presynaptic protein) immunolabeling showing synaptic terminals (white spots) around an SPL neuron (asterisk) Co-localization (arrows) of  7 nAChR subunit and synaptotagmin in processes of an LGNv neuron