Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 296 (5573): 1706-1709

Copyright © 2002 by the American Association for the Advancement of Science

Operant Reward Learning in Aplysia: Neuronal Correlates and Mechanisms

Björn Brembs,* Fred D. Lorenzetti,* Fredy D. Reyes, Douglas A. Baxter, John H. Byrnedagger

Operant conditioning is a form of associative learning through which an animal learns about the consequences of its behavior. Here, we report an appetitive operant conditioning procedure in Aplysia that induces long-term memory. Biophysical changes that accompanied the memory were found in an identified neuron (cell B51) that is considered critical for the expression of behavior that was rewarded. Similar cellular changes in B51 were produced by contingent reinforcement of B51 with dopamine in a single-cell analog of the operant procedure. These findings allow for the detailed analysis of the cellular and molecular processes underlying operant conditioning.

Department of Neurobiology and Anatomy, W. M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas-Houston Medical School, Houston, TX 77030, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: john.h.byrne{at}

The less things change, the more they are different: contributions of long-term synaptic plasticity and homeostasis to memory.
S. Schacher and J.-Y. Hu (2014)
Learn. Mem. 21, 128-134
   Abstract »    Full Text »    PDF »
Implication of dopaminergic modulation in operant reward learning and the induction of compulsive-like feeding behavior in Aplysia.
A. Bedecarrats, C. Cornet, J. Simmers, and R. Nargeot (2013)
Learn. Mem. 20, 318-327
   Abstract »    Full Text »    PDF »
Effects of aversive stimuli beyond defensive neural circuits: Reduced excitability in an identified neuron critical for feeding in Aplysia.
M. E. Shields-Johnson, J. S. Hernandez, C. Torno, K. M. Adams, M. L. Wainwright, and R. Mozzachiodi (2012)
Learn. Mem. 20, 1-5
   Abstract »    Full Text »    PDF »
Mechanisms or metaphors? The emptiness of evolutionary psychological explanations.
E. E. Gantt, B. S. Melling, and J. S. Reber (2012)
Theory Psychology 22, 823-841
   Abstract »    PDF »
Rapid and persistent suppression of feeding behavior induced by sensitization training in Aplysia.
A. Acheampong, K. Kelly, M. Shields-Johnson, J. Hajovsky, M. Wainwright, and R. Mozzachiodi (2012)
Learn. Mem. 19, 159-163
   Abstract »    Full Text »    PDF »
Classical Conditioning Analog Enhanced Acetylcholine Responses But Reduced Excitability of an Identified Neuron.
F. D. Lorenzetti, D. A. Baxter, and J. H. Byrne (2011)
J. Neurosci. 31, 14789-14793
   Abstract »    Full Text »    PDF »
L-arginine via nitric oxide is an inhibitory feedback modulator of Aplysia feeding.
N. Miller, R. Saada, S. Markovich, I. Hurwitz, and A. J. Susswein (2011)
J Neurophysiol 105, 1642-1650
   Abstract »    Full Text »    PDF »
Towards a scientific concept of free will as a biological trait: spontaneous actions and decision-making in invertebrates.
B. Brembs (2011)
Proc R Soc B 278, 930-939
   Abstract »    Full Text »    PDF »
A Homolog of the Vertebrate Pituitary Adenylate Cyclase-Activating Polypeptide Is Both Necessary and Instructive for the Rapid Formation of Associative Memory in an Invertebrate.
Z. Pirger, Z. Laszlo, I. Kemenes, G. Toth, D. Reglodi, and G. Kemenes (2010)
J. Neurosci. 30, 13766-13773
   Abstract »    Full Text »    PDF »
Composite Modulatory Feedforward Loop Contributes to the Establishment of a Network State.
J. S. Wu, F. S. Vilim, N. G. Hatcher, M. R. Due, J. V. Sweedler, K. R. Weiss, and J. Jing (2010)
J Neurophysiol 103, 2174-2184
   Abstract »    Full Text »    PDF »
Nitric oxide and histamine signal attempts to swallow: A component of learning that food is inedible in Aplysia.
A. Katzoff, N. Miller, and A. J. Susswein (2010)
Learn. Mem. 17, 50-62
   Abstract »    Full Text »    PDF »
Novel neural correlates of operant conditioning in normal and differentially reared Lymnaea.
A. M. Khan and G. E. Spencer (2009)
J. Exp. Biol. 212, 922-933
   Abstract »    Full Text »    PDF »
Training with inedible food in Aplysia causes expression of C/EBP in the buccal but not cerebral ganglion.
D. Levitan, L. C. Lyons, A. Perelman, C. L. Green, B. Motro, A. Eskin, and A. J. Susswein (2008)
Learn. Mem. 15, 412-416
   Abstract »    Full Text »    PDF »
Currents Contributing to Decision Making in Neurons B31/B32 of Aplysia.
I. Hurwitz, A. Ophir, A. Korngreen, J. Koester, and A. J. Susswein (2008)
J Neurophysiol 99, 814-830
   Abstract »    Full Text »    PDF »
Transient Mitogen-Activated Protein Kinase Activation Is Confined to a Narrow Temporal Window Required for the Induction of Two-Trial Long-Term Memory in Aplysia.
G. T. Philips, E. I. Tzvetkova, and T. J. Carew (2007)
J. Neurosci. 27, 13701-13705
   Abstract »    Full Text »    PDF »
Structure and function of haemocytes in two marine gastropods, Megathura crenulata and Aplysia californica.
G. G. Martin, C. T. Oakes, H. R. Tousignant, H. Crabtree, and R. Yamakawa (2007)
J. Mollus. Stud. 73, 355-365
   Abstract »    Full Text »    PDF »
Behavioral and In Vitro Correlates of Compulsive-Like Food Seeking Induced by Operant Conditioning in Aplysia.
R. Nargeot, C. Petrissans, and J. Simmers (2007)
J. Neurosci. 27, 8059-8070
   Abstract »    Full Text »    PDF »
Endogenous Motor Neuron Properties Contribute to a Program-Specific Phase of Activity in the Multifunctional Feeding Central Pattern Generator of Aplysia.
G. E. Serrano, C. Martinez-Rubio, and M. W. Miller (2007)
J Neurophysiol 98, 29-42
   Abstract »    Full Text »    PDF »
Feeding behavior of Aplysia: A model system for comparing cellular mechanisms of classical and operant conditioning.
D. A. Baxter and J. H. Byrne (2006)
Learn. Mem. 13, 669-680
   Abstract »    Full Text »    PDF »
Context and occasion setting in Drosophila visual learning..
B. Brembs and J. Wiener (2006)
Learn. Mem. 13, 618-628
   Abstract »    Full Text »    PDF »
Target-Specific Regulation of Synaptic Efficacy in the Feeding Central Pattern Generator of Aplysia: Potential Substrates for Behavioral Plasticity?.
M. Diaz-Rios and M. W. Miller (2006)
Biol. Bull. 210, 215-229
   Abstract »    Full Text »    PDF »
Rostral Ganglia Are Required for Induction But Not Expression of Crayfish Escape Reflex Habituation: Role of Higher Centers in Reprogramming Low-Level Circuits.
D. Shirinyan, T. Teshiba, K. Taylor, P. O'Neill, S. C. Lee, and F. B. Krasne (2006)
J Neurophysiol 95, 2721-2724
   Abstract »    Full Text »    PDF »
Operant Conditioning of Gill Withdrawal in Aplysia.
R. D. Hawkins, G. A. Clark, and E. R. Kandel (2006)
J. Neurosci. 26, 2443-2448
   Abstract »    Full Text »    PDF »
Individual differences in dopamine efflux in nucleus accumbens shell and core during instrumental learning..
J. Cheng and M. G.P. Feenstra (2006)
Learn. Mem. 13, 168-177
   Abstract »    Full Text »    PDF »
Perturbation of the activity of a single identified neuron affects long-term memory formation in a molluscan semi-intact preparation.
M. R. Lowe and G. E. Spencer (2006)
J. Exp. Biol. 209, 711-721
   Abstract »    Full Text »    PDF »
Human Neural Learning Depends on Reward Prediction Errors in the Blocking Paradigm.
P. N. Tobler, J. P. O'Doherty, R. J. Dolan, and W. Schultz (2006)
J Neurophysiol 95, 301-310
   Abstract »    Full Text »    PDF »
Reinforcement in an in vitro analog of appetitive classical conditioning of feeding behavior in Aplysia: Blockade by a dopamine antagonist.
F. D. Reyes, R. Mozzachiodi, D. A. Baxter, and J. H. Byrne (2005)
Learn. Mem. 12, 216-220
   Abstract »    Full Text »    PDF »
Rapid Dopaminergic Signaling by Interneurons That Contain Markers for Catecholamines and GABA in the Feeding Circuitry of Aplysia.
M. Diaz-Rios and M. W. Miller (2005)
J Neurophysiol 93, 2142-2156
   Abstract »    Full Text »    PDF »
Extending In Vitro Conditioning in Aplysia to Analyze Operant and Classical Processes in the Same Preparation.
B. Brembs, D. A. Baxter, and J. H. Byrne (2004)
Learn. Mem. 11, 412-420
   Abstract »    Full Text »    PDF »
Operant Reward Learning in Aplysia.
B. Brembs (2003)
Current Directions in Psychological Science 12, 218-221
   Abstract »    Full Text »    PDF »
Long-Term Plasticity of Intrinsic Excitability: Learning Rules and Mechanisms.
G. Daoudal and D. Debanne (2003)
Learn. Mem. 10, 456-465
   Abstract »    Full Text »    PDF »
In Vitro Analog of Classical Conditioning of Feeding Behavior in Aplysia.
R. Mozzachiodi, H. A. Lechner, D. A. Baxter, and J. H. Byrne (2003)
Learn. Mem. 10, 478-494
   Abstract »    Full Text »    PDF »
A Newly Identified Buccal Interneuron Initiates and Modulates Feeding Motor Programs in Aplysia.
N. C. Dembrow, J. Jing, A. Proekt, A. Romero, F. S. Vilim, E. C. Cropper, and K. R. Weiss (2003)
J Neurophysiol 90, 2190-2204
   Abstract »    Full Text »    PDF »
Multiple Serotonergic Mechanisms Contributing to Sensitization in Aplysia: Evidence of Diverse Serotonin Receptor Subtypes.
D. Barbas, L. DesGroseillers, V. F. Castellucci, T. J. Carew, and S. Marinesco (2003)
Learn. Mem. 10, 373-386
   Abstract »    Full Text »    PDF »
Voltage-Dependent Switching of Sensorimotor Integration by a Lobster Central Pattern Generator.
R. Nargeot (2003)
J. Neurosci. 23, 4803-4808
   Abstract »    Full Text »    PDF »
Nitric Oxide Is Necessary for Multiple Memory Processes after Learning That a Food Is Inedible in Aplysia.
A. Katzoff, T. Ben-Gedalya, and A. J. Susswein (2002)
J. Neurosci. 22, 9581-9594
   Abstract »    Full Text »    PDF »
NEUROSCIENCE: A Bite to Remember.
C. H. Rankin (2002)
Science 296, 1624-1625
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882