Nicotinic acetylcholine receptors (nAChRs) are located in many brain regions and are known to participate in critical tasks including learning, memory, and vision. Activation of nAChRs by exogenous application of acetylcholine (ACh) or nicotine produces diverse functional responses. Presynaptic nAChRs mediate enhanced release of several neurotransmitters. Activation of postsynaptic nAChRs produces excitatory responses that can be sufficient to elicit action potentials in neurons. Although these findings are critically important, relatively little is known concerning the functional effects of endogenously released acetylcholine and the cholinergic modulation of physiologically important pathways in the visual system and basal ganglia. The major goal of this proposal is to enhance our understanding of the overall impact of nicotinic receptor activation by endogenous ACh on synaptic transmission at defined sites within brain slices. Key featuresof our approach include the use of well-characterized model systems (ventral lateral geniculate and lateral spiriform nucleus) with robust presynaptic and postsynaptic nicotinic responses, and our ability to examine the physiological significance of nicotinic modulation resulting from the electrically stimulated release of endogenous ACh. Localization of nAChR subtypes within the circuitry of these brain regions will allow us to construct a model for their roles in the processing of incoming information and the output of projection neurons. Functional studies will be done using whole cell patch-clamp electrophysiological recordingsof single neuron activity in brain slices. The impact of cholinergic transmission at both nicotinic and muscarinic receptors will be evaluated in relationship to glutamatergic and GABAergic transmission. We will examine both short term and long term effects of activation of nicotinic receptors, and study developmental regulation of cholinergic modulation. Cigarette smoking causes over 400,000 premature deaths per year in the USA. Nicotine is the addictive principle in tobacco, and acts at central nAChRs to create dependence. Nicotinic receptors also mediate enhanced cognition and visual attention, and are reduced in number in several neurodegenerative diseases. They are present at high densities in the visual system and basal ganglia, but their functional roles in these systems are poorly understood. This project will expand our knowledge of the roles of these receptors.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Stewart, Randall R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
George Washington University
Schools of Medicine
United States
Zip Code
Guo, J-Z; Sorenson, E M; Chiappinelli, V A (2010) Cholinergic modulation of non-N-methyl-D-aspartic acid glutamatergic transmission in the chick ventral lateral geniculate nucleus. Neuroscience 166:604-14
Liu, Y-B; Guo, J-Z; Chiappinelli, V A (2007) Nicotinic receptor-mediated biphasic effect on neuronal excitability in chick lateral spiriform neurons. Neuroscience 148:1004-14
Guo, Jian-Zhong; Liu, Yingbing; Sorenson, Eva M et al. (2005) Synaptically released and exogenous ACh activates different nicotinic receptors to enhance evoked glutamatergic transmission in the lateral geniculate nucleus. J Neurophysiol 94:2549-60
Nong, Yi; Sorenson, Eva M; Chiappinelli, Vincent A (2003) Opioid receptor activation attenuates nicotinic enhancement of spontaneous GABA release in lateral spiriform nucleus of the chick. Brain Res 961:45-52
Zhu, P J; Chiappinelli, V A (2002) Nicotinic receptors mediate increased GABA release in brain through a tetrodotoxin-insensitive mechanism during prolonged exposure to nicotine. Neuroscience 115:137-44
Guo, J-Z; Chiappinelli, V A (2002) A novel choline-sensitive nicotinic receptor subtype that mediates enhanced GABA release in the chick ventral lateral geniculate nucleus. Neuroscience 110:505-13
Guo, J; Chiappinelli, V A (2001) Distinct muscarinic receptors enhance spontaneous GABA release and inhibit electrically evoked GABAergic synaptic transmission in the chick lateral spiriform nucleus. Neuroscience 104:1057-66
Sorenson, E M; El-Bogdadi, D G; Nong, Y et al. (2001) alpha7-Containing nicotinic receptors are segregated to the somatodendritic membrane of the cholinergic neurons in the avian nucleus semilunaris. Neuroscience 103:541-50
Guo, J Z; Chiappinelli, V A (2000) Muscarinic receptors mediate enhancement of spontaneous GABA release in the chick brain. Neuroscience 95:273-82
Tredway, T L; Guo, J Z; Chiappinelli, V A (1999) N-type voltage-dependent calcium channels mediate the nicotinic enhancement of GABA release in chick brain. J Neurophysiol 81:447-54

Showing the most recent 10 out of 41 publications