Modulation of Synaptic Transmission in the CNS by Acetylcholine

Regehr, Wade G.

Abstract

Clarifying the function of acetylcholine (ACh) receptors in the brain promises to have important implications for understanding Alzheimer's disease, addiction to nicotine, learning and memory. The overall goal of this proposal is to determine how ACh affects synapses and to ascertain the consequences of changes in synaptic strength. Initial experiments will be conducted in the hippocampus, a brain region involved in learning and memory. ACh is known to play an important modulatory role in the hippocampus by activating different types of receptors. There are, however, many unanswered questions regarding the mechanisms of the modulation and their physiological consequences. One major goal of the proposal is to clarify the types of synaptic connections that are regulated by ACh to determine the mechanisms of the modulation. Another goal is to determine the ultimate effects of such changes in synaptic strength for conditions that would be encountered in different behavioral states in the brain.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Neurological Disorders and Stroke (NINDS)
• Type: Research Program Projects (P01)
• Project #: 5P01NS038312-04
• Application #: 6565269
• Project Start: 2001-12-01
• Project End: 2002-11-30
• Support Year: 4
• Fiscal Year: 2002
• Total Cost: $295,873

Institution

• Name: Harvard University
• DUNS #: 082359691
• City: Boston
• State: MA
• Country: United States
• Zip Code: 02115

Publications

Richards, Kathryn S; Swensen, Andrew M; Lipscombe, Diane et al. (2007) Novel CaV2.1 clone replicates many properties of Purkinje cell CaV2.1 current. Eur J Neurosci 26:2950-61

McDonough, Stefan I; Mori, Yasuo; Bean, Bruce P (2005) FPL 64176 modification of Ca(V)1.2 L-type calcium channels: dissociation of effects on ionic current and gating current. Biophys J 88:211-23

Blitz, Dawn M; Regehr, Wade G (2003) Retinogeniculate synaptic properties controlling spike number and timing in relay neurons. J Neurophysiol 90:2438-50

Blair, Nathaniel T; Bean, Bruce P (2003) Role of tetrodotoxin-resistant Na+ current slow inactivation in adaptation of action potential firing in small-diameter dorsal root ganglion neurons. J Neurosci 23:10338-50

Do, Michael Tri H; Bean, Bruce P (2003) Subthreshold sodium currents and pacemaking of subthalamic neurons: modulation by slow inactivation. Neuron 39:109-20

Martina, Marco; Yao, Gui Lan; Bean, Bruce P (2003) Properties and functional role of voltage-dependent potassium channels in dendrites of rat cerebellar Purkinje neurons. J Neurosci 23:5698-707

Swensen, Andrew M; Bean, Bruce P (2003) Ionic mechanisms of burst firing in dissociated Purkinje neurons. J Neurosci 23:9650-63

Chen, Chinfei; Blitz, Dawn M; Regehr, Wade G (2002) Contributions of receptor desensitization and saturation to plasticity at the retinogeniculate synapse. Neuron 33:779-88

Mitterdorfer, Jorg; Bean, Bruce P (2002) Potassium currents during the action potential of hippocampal CA3 neurons. J Neurosci 22:10106-15

Blair, Nathaniel T; Bean, Bruce P (2002) Roles of tetrodotoxin (TTX)-sensitive Na+ current, TTX-resistant Na+ current, and Ca2+ current in the action potentials of nociceptive sensory neurons. J Neurosci 22:10277-90