Amygdala Neurons Differentially Encode Motivation and Reinforcement

Lesion studies demonstrate that the basolateral amygdala complex (BLA) is important for assigning motivational significance to sensory stimuli, but little is known about how this information is encoded. We used in vivo electrophysiology procedures to investigate how the amygdala encodes motivating and reinforcing properties of cues that induce reinstatement of reward-seeking behavior. Two groups of rats were trained to respond to a sucrose reward. The “paired” group was trained with a reward-predictive cue, whereas the “unpaired” group was trained with a randomly presented cue. Both groups underwent identical extinction and reinstatement procedures during which the reward was withheld. The proportion of neurons that were phasically cue responsive during reinstatement was significantly higher in the paired group (46 of 100) than in the unpaired group (8 of 112). Cues that induce reward-seeking behavior can do so by acting as incentives or reinforcers. Distinct populations of neurons responded to the cue in trials in which the cue acted as an incentive, triggering a motivated reward-seeking state, or as a reinforcer, supporting continued instrumental responding. The incentive motivation-encoding population of neurons (34 of 46 cue-responsive neurons; 74%) extinguished in temporal agreement with a decrease in the rate of instrumental responding. The conditioned reinforcement-encoding population of neurons (12 of 46 cue-responsive neurons; 26%) maintained their response for the duration of cue-reinforced instrumental responding. These data demonstrate that separate populations of cue-responsive neurons in the BLA encode the motivating or reinforcing properties of a cue previously associated with a reward.

[1]  T. Robbins,et al.  Involvement of the amygdala in stimulus-reward associations: Interaction with the ventral striatum , 1989, Neuroscience.

[2]  T. Robbins,et al.  Acquisition, maintenance and reinstatement of intravenous cocaine self-administration under a second-order schedule of reinforcement in rats: effects of conditioned cues and continuous access to cocaine , 1998, Psychopharmacology.

[3]  R. See,et al.  Lesions of the basolateral amygdala abolish the ability of drug associated cues to reinstate responding during withdrawal from self-administered cocaine , 1997, Behavioural Brain Research.

[4]  Anna Rose Childress,et al.  Conditioning factors in drug abuse: can they explain compulsion? , 1998, Journal of psychopharmacology.

[5]  J. D. McGaugh.  Memory consolidation and the amygdala: a systems perspective , 2002, Trends in Neurosciences.

[6]  Geoffrey Schoenbaum,et al.  Rapid Associative Encoding in Basolateral Amygdala Depends on Connections with Orbitofrontal Cortex , 2005, Neuron.

[7]  Joseph J. Paton,et al.  The primate amygdala represents the positive and negative value of visual stimuli during learning , 2006, Nature.

[8]  David H. Epstein,et al.  Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure , 2006, Psychopharmacology.

[9]  Joselyn McLaughlin,et al.  Selective inactivation of the dorsomedial prefrontal cortex and the basolateral amygdala attenuates conditioned-cued reinstatement of extinguished cocaine-seeking behavior in rats , 2003, Psychopharmacology.

[10]  G. Schoenbaum,et al.  Encoding Predicted Outcome and Acquired Value in Orbitofrontal Cortex during Cue Sampling Depends upon Input from Basolateral Amygdala , 2003, Neuron.

[11]  B. Balleine,et al.  Double Dissociation of Basolateral and Central Amygdala Lesions on the General and Outcome-Specific Forms of Pavlovian-Instrumental Transfer , 2005, The Journal of Neuroscience.

[12]  T. Robbins,et al.  Interactions between the amygdala and ventral striatum in stimulus-reward associations: Studies using a second-order schedule of sexual reinforcement , 1989, Neuroscience.

[13]  H. Fields,et al.  Basolateral amygdala lesions impair both cue- and cocaine-induced reinstatement in animals trained on a discriminative stimulus task , 2003, Neuroscience.

[14]  A. Grace,et al.  The Prefrontal Cortex Regulates Lateral Amygdala Neuronal Plasticity and Responses to Previously Conditioned Stimuli , 2003, The Journal of Neuroscience.

[15]  Michael Davis,et al.  The role of the amygdala in conditioned fear. , 1992 .

[16]  K. Berridge,et al.  Parsing reward , 2003, Trends in Neurosciences.

[17]  G. Schoenbaum,et al.  Functions of the Amygdala and Related Forebrain Areas in Attention and Cognition , 1999, Annals of the New York Academy of Sciences.

[18]  H. Groenewegen,et al.  Basal amygdaloid complex afferents to the rat nucleus accumbens are compartmentally organized , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  L. Swanson.  The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[20]  M. Cassell,et al.  Cortical, thalamic, and amygdaloid connections of the anterior and posterior insular cortices , 1998, The Journal of comparative neurology.

[21]  A. McDonald.  Neurons of the lateral and basolateral amygdaloid nuclei: A golgi study in the rat , 1982, The Journal of comparative neurology.

[22]  Y. Shaham,et al.  Effect of cocaine and sucrose withdrawal period on extinction behavior, cue-induced reinstatement, and protein levels of the dopamine transporter and tyrosine hydroxylase in limbic and cortical areas in rats , 2002, Behavioural pharmacology.

[23]  Anthony A Grace,et al.  A Subpopulation of Neurons in the Medial Prefrontal Cortex Encodes Emotional Learning with Burst and Frequency Codes through a Dopamine D4 Receptor-Dependent Basolateral Amygdala Input , 2005, The Journal of Neuroscience.

[24]  P. Kalivas,et al.  Brain circuitry and the reinstatement of cocaine-seeking behavior , 2003, Psychopharmacology.

[25]  R. Carelli,et al.  Basolateral Amygdala Neurons Encode Cocaine Self-Administration and Cocaine-Associated Cues , 2003, The Journal of Neuroscience.

[26]  R. A. Fuchs,et al.  Basolateral amygdala inactivation abolishes conditioned stimulus- and heroin-induced reinstatement of extinguished heroin-seeking behavior in rats , 2002, Psychopharmacology.

[27]  Michael Davis,et al.  Different mechanisms of fear extinction dependent on length of time since fear acquisition. , 2006, Learning & memory.

[28]  T. Ono,et al.  Neuronal responsiveness to various sensory stimuli, and associative learning in the rat amygdala , 1995, Neuroscience.

[29]  R. Ehrman,et al.  Conditioned responses to cocaine-related stimuli in cocaine abuse patients , 2005, Psychopharmacology.

[30]  B. Balleine,et al.  The Effect of Lesions of the Basolateral Amygdala on Instrumental Conditioning , 2003, The Journal of Neuroscience.

[31]  R. Vertes.  Differential projections of the infralimbic and prelimbic cortex in the rat , 2004, Synapse.

[32]  G. Schoenbaum,et al.  Neural Encoding in Orbitofrontal Cortex and Basolateral Amygdala during Olfactory Discrimination Learning , 1999, The Journal of Neuroscience.

[33]  Davis Wm,et al.  Role of conditioned reinforcers in the initiation, maintenance and extinction of drug-seeking behavior. , 1976 .

[34]  E. Murray,et al.  Control of Response Selection by Reinforcer Value Requires Interaction of Amygdala and Orbital Prefrontal Cortex , 2000, The Journal of Neuroscience.

[35]  R. Ehrman,et al.  Conditioned craving and arousal in cocaine addiction: a preliminary report. , 1988, NIDA research monograph.

[36]  Joseph E LeDoux.  Emotional networks and motor control: a fearful view. , 1996, Progress in brain research.

[37]  W. M. Davis,et al.  Role of conditioned reinforcers in the initiation, maintenance and extinction of drug-seeking behavior , 1976, The Pavlovian journal of biological science.

[38]  P. Janak,et al.  Comparison of reinstatement of ethanol- and sucrose-seeking by conditioned stimuli and priming injections of allopregnanolone after extinction in rats , 2003, Psychopharmacology.

[39]  T. Robbins,et al.  Second-order schedules of drug reinforcement in rats and monkeys: measurement of reinforcing efficacy and drug-seeking behaviour , 2000, Psychopharmacology.

[40]  W. Nauta,et al.  The amygdalostriatal projection in the rat—an anatomical study by anterograde and retrograde tracing methods , 1982, Neuroscience.

[41]  A. McDonald,et al.  Neuronal organization of the lateral and basolateral amygdaloid nuclei in the rat , 1984, The Journal of comparative neurology.

[42]  Joseph E LeDoux,et al.  Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: Parallel recordings in the freely behaving rat , 1995, Neuron.

[43]  Barry Setlow,et al.  Disconnection of the basolateral amygdala complex and nucleus accumbens impairs appetitive pavlovian second-order conditioned responses. , 2002, Behavioral neuroscience.

[44]  M. Washburn,et al.  Electrophysiological and morphological properties of rat basolateral amygdaloid neurons in vitro , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[45]  M. Reivich,et al.  Limbic activation during cue-induced cocaine craving. , 1999, The American journal of psychiatry.

[46]  T. Robbins,et al.  Neural systems of reinforcement for drug addiction: from actions to habits to compulsion , 2005, Nature Neuroscience.

[47]  Theresa M. Desrochers,et al.  Two different lateral amygdala cell populations contribute to the initiation and storage of memory , 2001, Nature Neuroscience.

[48]  H. Kita,et al.  Amygdaloid projections to the frontal cortex and the striatum in the rat , 1990, The Journal of comparative neurology.

[49]  E. Asprodini,et al.  Intracellular recordings from morphologically identified neurons of the basolateral amygdala. , 1993, Journal of neurophysiology.