Memory and addiction

Memories are formed when neurons alter their functional properties in response to experience. Addiction occurs when neural and behavioural plasticity is induced by chronic exposure to neuroactive drugs. Since C. elegans exhibits well-characterized forms of learning and memory, it offers the possibility of understanding in neural and molecular detail how memory and addiction paradigms cause changes in a whole animal's behaviour.

A form of behavioural plasticity we have focused on is nicotine addiction. Nicotine addiction is thought to result from long-term adaptive changes in the activity and expression of nicotinic acetylcholine receptors in the brain. However, the molecular and neuronal mechanisms that underlie these processes remain poorly understood. We have investigated the roles of nicotinic receptors in C. elegans behaviours, and identified genes involved in regulating nicotinic receptor function and abundance. We have also used proteomics to identify novel molecules that interact with nicotinic receptor complexes and affect their activity in vivo.

Recent papers:

Learning and memory:

Kindt KS, Quast KB, Giles AG, De S, Hendrey D, Nicastro I, Rankin CH, Schafer WR (2007) "Dopamine mediates context-dependent modulation of sensory plasticity in C. elegans" Neuron 55: 662-676. Supplemental material.

Tomioka M, Adachi T, Suzuki H, Kunitomo H, Schafer WR, Iino Y (2006) "The insulin/PI3 –kinase pathway regulates salt chemotaxis learning in Caenorhabditis elegans" Neuron 51: 613-626.

Sanyal S, Wintle RF, Kindt K, Nuttley WM, Arvan R, Fitzmaurice P, Bigras E, Merz D, Hebert TE, van der Kooy D, Schafer WR, Culotti JG and Van Tol HHM. (2004) "Dopamine modulates the plasticity of mechanosensory responses in C. elegans" EMBO Journal 23: 473-482.

Waggoner LE, Dickinson KA, Poole DS, Tabuse Y, Miwa J, Schafer WR. (2000) “Long-term nicotine adaptation in Caenorhabditis elegans involves PKC-dependent changes in nicotinic receptor abundance” J. Neurosci. 20: 8802-8811.\

Schafer, WR, Kenyon C. (1995) "A calcium channel homologue required for adaptation to dopamine and serotonin in Caenorhabditis elegans." Nature 375: 73-78

Other nicotine:

Eimer S, Gottschalk A, Hengartner M, Horvitz HR, Richmond J, Schafer WR, Bessereau J-L (2007) "Regulation of nicotinic receptor trafficking by the transmembrane Golgi protein UNC-50" EMBO J 26: 4313-4323. Supplemental material.

Matta SG, Balfour DJ, Benowitz NL, Boyd RT, Buccafusco JJ, Caggiula AR, Craig CR, Collins AC, Damaj MI, Donny EC, Gardiner PS, Grady SR, Heberlein U, Leonard SS, Levin ED, Lukas RJ, Markou A, Marks MJ, McCallum SE, Parameswaran N, Perkins KA, Picciotto MR, Quik M, Rose JE, Rothenfluh A, Schafer WR, Stolerman IP, Tyndale RF, Wehner JM, Zirger JM. (2006) "Guidelines on nicotine dose selection for in vivo research". (2006) Psychopharmacology (Berl). Epub 2006 Aug 9

Gottschalk A, Schafer WR (2006) "Visualization of integral and peripheral cell surface proteins in live Caenorhabditis elegans" J Neurosci Methods. 154: 68-79 Epub 2006 Feb 6

Gottschalk A, Almedom, RB, Schedletzky T, Anderson AD, Yates JR III, Schafer WR (2005) "Identification and characterization of novel nicotinic receptor-associated proteins in Caenorhabditis elegans." EMBO Journal 24:2566-78. Epub 2005 Jun 30. +supplementary material

McKay, Raizen D, Gottschalk A, Schafer WR, Avery L (2004) "eat-2 and eat-18 are required for nicotinic neurotransmission in the C. elegans pharynx Genetics 166: 161-169.

Kim J, Poole DS, Waggoner LE, Kempf A, Ramirez DS, Treschow PA, Schafer WR (2001) “Genes affecting affecting the activity of nicotinic receptors involved in Caenorhabditis elegans egg-laying behavior” Genetics 157: 1599-1610.