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Exploring Neuronal Nicotinic Receptors: Role in Synaptic Transmission and Development

The research focuses on the functional properties of neuronal nicotinic receptors (nAChRs) and their role in synaptic transmission within the central nervous system (CNS) during development. Combining electrophysiological and morphological methods, the study utilizes patch-clamp recordings from visualized nerve cells in living brain slices to analyze synaptic responses. Key findings include the impact of electrical stimulation on cholinergic inputs, revealing significant increases in glutamatergic currents and insights into receptor subtypes. The principal investigators include Vince Chiappinelli, Jian-Zhong Guo, and Eva Sorenson.

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Exploring Neuronal Nicotinic Receptors: Role in Synaptic Transmission and Development

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

  2. 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 Principal Investigator: Vince Chiappinelli Co-Principal Investigator: Jian-Zhong Guo Co-Principal Investigator: Eva Sorenson Consultant: David Perry Consultant: Michael McIntosh (Univ. Utah)

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

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

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

  6. Schematic diagram of selected circuitry within the ventral Lateral Geniculate Nucleus (LGNv) a4* a6* a7* a6* Locations of nicotinic receptors are indicated by asterisks. Pharmacological tools allow identification of subtypes of nAChRs.

  7. Synaptotagmin (a presynaptic protein) immunolabeling showing synaptic terminals (white spots) around an SPL neuron (asterisk) 125I-a-Conotoxin MII autoradiography in rat brain: LGN and optic tract heavily labeled revealing a6* receptor locations A: Autoradiography of a6* nicotinic receptors B and C:Confocal Microscopy showing Co-Localization of Synaptotagmin and a7 nicotinic receptor subunit Co-localization (arrows) of a7 nAChR subunitand synaptotagmin in processes of an LGNv neuron

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