Vincent A. Chiappinelli, Ph.D.The Ralph E. Loewy ProfessorChair, Dept. of Pharmacology &

Physiology

Tel: 202-994-3541phmvac@gwumc.edu

Principal Investigator: Vince ChiappinelliCo-Principal Investigator: Jian-Zhong GuoCo-Principal Investigator: Eva SorensonConsultant: David PerryConsultant: Michael McIntosh (Univ. Utah)

FUNCTIONAL PROPERTIES OF NEURONAL NICOTINIC RECEPTORS

NIH Competitive Renewal – 21st 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 DHE 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 receptorsB 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