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Sidman Instrumental Avoidance Initially Depends on Lateral and Basal Amygdala and Is Constrained by Central Amygdala-Mediated Pavlovian Processes

  • Gabriel Lázaro-Muñoz
    Affiliations
    WM Keck Foundation Laboratory of Neurobiology, Center for Neural Science, New York University, New York, New York
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  • Joseph E. LeDoux
    Affiliations
    WM Keck Foundation Laboratory of Neurobiology, Center for Neural Science, New York University, New York, New York

    Department of Psychology, New York University, New York, New York

    Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York

    Emotional Brain Institute, New York University, New York, New York
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  • Christopher K. Cain
    Correspondence
    Address correspondence to Christopher K. Cain, Ph.D., Center for Neural Science, New York University, 4 Washington Place, Room 809, New York, NY 10003
    Affiliations
    WM Keck Foundation Laboratory of Neurobiology, Center for Neural Science, New York University, New York, New York
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      Background

      The lateral (LA) and central (CE), but not basal (B), amygdala nuclei are necessary for reactive Pavlovian fear responses such as freezing. The amygdala also plays a key role in the acquisition and expression of active instrumental defensive behaviors, but little is known about the specific roles of amygdala nuclei. Using a Sidman active avoidance (AA) task, we examined the necessity of LA, B, and CE for learning and performance. Pavlovian freezing was simultaneously assessed to examine the contributions of amygdala nuclei to the transition from reactive to active defensive responding.

      Methods

      Rats received electrolytic lesions of LA, CE, or B before AA training, or following overtraining. Rats that expressed low levels of AA performance during training received bilateral electrolytic lesions to CE to eliminate competing freezing reactions and rescue AA. AA performance and freezing were assessed.

      Results

      Damage to LA and B, but not CE, impaired the acquisition of AA. Performance of AA became amygdala-independent following overtraining. CE lesions abolished Pavlovian freezing and rescued instrumental AA performance in rats that expressed low levels of avoidance responses and high levels of freezing during training.

      Conclusions

      Although the acquisition of Pavlovian fear depends on LA and CE, but not B, acquisition of instrumental AA is dependent on LA and B, but not CE. CE-dependent Pavlovian processes that control freezing can constrain avoidance behavior. Performance of well-trained AA becomes independent of all three amygdala nuclei. Thus, it appears that different output pathways of LA mediate reactive and active conditioned defensive responding.

      Key Words

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      References

        • Bolles R.C.
        • Collier A.C.
        The effect of predictive cues on freezing in rats.
        Anim Learn Behav. 1976; 4: 6-8
        • Hirsh S.M.
        • Bolles R.C.
        On the ability of prey to recognize predators.
        Z Fur Tierpsychol. 1980; 54: 71-84
        • Fanselow M.S.
        • Lester L.S.
        A functional behavioristic approach to aversively motivated behavior: Imminence as a determinant of the topography of defensive behavior.
        in: Bolles R.C. Bleecher M.D. Evolution and Learning. Erlbaum, Hillsdale, NJ1988: 185-211
        • Bolles R.C.
        Species-specific defense reactions and avoidance learning.
        Psychol Rev. 1970; 77: 32-48
        • Blanchard R.J.
        • Flannelly K.J.
        • Blanchard D.C.
        Defensive behaviors of laboratory and wild Rattus norvegicus.
        J Comp Psychol. 1986; 100: 101-107
        • Solomon R.L.
        • Wynne L.C.
        Traumatic avoidance learning: The principles of anxiety conservation and partial irreversibility.
        Psychol Rev. 1954; 61: 353-385
        • Cain C.K.
        • LeDoux J.E.
        Escape from fear: A detailed behavioral analysis of two atypical responses reinforced by CS termination.
        J Exp Psych: Anim Behav Process. 2007; 33: 451-463
        • Rodrigues S.M.
        • Ledoux J.E.
        • Sapolsky R.M.
        The influence of stress hormones on fear circuitry.
        Annu Rev Neurosci. 2009; 32: 289-313
        • Roozendaal B.
        • McEwen B.S.
        • Chattarji S.
        Stress, memory and the amygdala.
        Nat Rev Neurosci. 2009; 10: 423-433
        • Sapolsky R.M.
        The influence of social hierarchy on primate health.
        Science. 2005; 308: 648-652
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders.
        4th ed. American Psychiatric Association, Washington, DC2000
        • NIMH
        Anxiety disorders.
        National Institute of Mental Health, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD2007
        • LeDoux J.E.
        • Gorman J.M.
        A call to action: Overcoming anxiety through active coping.
        Am J Psychiatry. 2001; 158: 1953-1955
        • van der Kolk B.A.
        Clinical implications of neuroscience research in PTSD.
        Ann N Y Acad Sci. 2006; 1071: 277-293
        • Cain C.K.
        • LeDoux J.E.
        Brain mechanisms of Pavlovian and instrumental aversive conditioning.
        in: Nutt D.J. Blanchard R.J. Blanchard D.C. Griebel G. Handbook of Anxiety and Fear. Vol 17. Elsevier Academic, Amsterdam2008: 103-125
        • Keay K.A.
        • Bandler R.
        Parallel circuits mediating distinct emotional coping reactions to different types of stress.
        Neurosci Biobehav Rev. 2001; 25: 669-678
        • Blanchard R.J.
        • Blanchard D.C.
        Innate and conditioned reactions to threat in rats with amygdaloid lesions.
        J Comp Physiol Psychol. 1972; 81: 281-290
        • Davis M.
        The role of the amygdala in conditioned and unconditioned fear and anxiety.
        in: Aggleton J.P. The Amygdala. Oxford University Press, Oxford, UK2000: 213-288
        • LeDoux J.E.
        Emotion circuits in the brain.
        Annu Rev Neurosci. 2000; 23: 155-184
        • Fanselow M.S.
        • Gale G.D.
        The amygdala, fear, and memory.
        Ann N Y Acad Sci. 2003; 985: 125-134
        • Paré D.
        • Royer S.
        • Smith Y.
        • Lang E.J.
        Contextual inhibitory gating of impulse traffic in the intra-amygdaloid network.
        Ann N Y Acad Sci. 2003; 985: 78-91
        • LeDoux J.E.
        The amygdala.
        Curr Biol. 2007; 17: 868-879
        • Fanselow M.S.
        • LeDoux J.E.
        Why we think plasticity underlying Pavlovian fear conditioning occurs in the basolateral amygdala.
        Neuron. 1999; 23: 229-232
        • Nader K.
        • Majidishad P.
        • Amorapanth P.
        • LeDoux J.E.
        Damage to the lateral and central, but not other, amygdaloid nuclei prevents the acquisition of auditory fear conditioning.
        Learn Mem. 2001; 8: 156-163
        • Gale G.D.
        • Anagnostaras S.G.
        • Godsil B.P.
        • Mitchell S.
        • Nozawa T.
        • Sage J.R.
        • et al.
        Role of the basolateral amygdala in the storage of fear memories across the adult lifetime of rats.
        Neuroscience. 2004; 24: 3810-3815
        • Wilensky A.E.
        • Schafe G.E.
        • Kristensen M.P.
        • LeDoux J.E.
        Rethinking the fear circuit: The central nucleus of the amygdala is required for the acquisition, consolidation, and expression of Pavlovian fear conditioning.
        J Neurosci. 2006; 26: 12387-12396
        • Maren S.
        Neurotoxic basolateral amygdala lesions impair learning and memory but not the performance of conditional fear in rats.
        J Neurosci. 1999; 19: 8696-8703
        • LeDoux J.E.
        • Cicchetti P.
        • Xagoraris A.
        • Romanski L.M.
        The lateral amygdaloid nucleus: Sensory interface of the amygdala in fear conditioning.
        J Neurosci. 1990; 10: 1062-1069
        • Campeau S.
        • Davis M.
        Involvement of the central nucleus and basolateral complex of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli.
        J Neurosci. 1995; 15: 2301-2311
        • Paré D.
        • Quirk G.J.
        • LeDoux J.E.
        New vistas on amygdala networks in conditioned fear.
        J Neurophysiol. 2004; 92: 1-9
        • Amorapanth P.
        • LeDoux J.E.
        • Nader K.
        Different lateral amygdala outputs mediate reactions and actions elicited by a fear-arousing stimulus.
        Nat Neurosci. 2000; 3: 74-79
        • Anglada-Figueroa D.
        • Quirk G.J.
        Lesions of the basal amygdala block expression of conditioned fear but not extinction.
        J Neurosci. 2005; 25: 9680-9685
        • Herry C.
        • Ciocchi S.
        • Senn V.
        • Demmou L.
        • Muller C.
        • Lüthi A.
        Switching on and off fear by distinct neuronal circuits.
        Nature. 2008; 454: 600-606
        • Goddard G.V.
        Functions of the amygdala.
        Psychol Rev. 1964; 62: 89-109
        • Sarter M.F.
        • Markowitsch H.J.
        Involvement of the amygdala in learning and memory: A critical review, with emphasis on anatomical relations.
        Behav Neurosci. 1985; 99: 342-380
        • Maren S.
        • Poremba A.
        • Gabriel M.
        Basolateral amygdaloid multi-unit neuronal correlates of discriminative avoidance learning in rabbits.
        Brain Res. 1991; 549: 311-316
        • Killcross S.
        • Robbins T.W.
        • Everitt B.J.
        Different types of fear-conditioned behaviour mediated by separate nuclei within amygdala.
        Nature. 1997; 388: 377-380
        • Poremba A.
        • Gabriel M.
        Amygdalar lesions block discriminative avoidance learning and cingulothalamic training-induced neuronal plasticity in rabbits.
        J Neurosci. 1997; 17: 5237-5244
        • Poremba A.
        • Gabriel M.
        Amygdala neurons mediate acquisition but not maintenance of instrumental avoidance behavior in rabbits.
        J Neurosci. 1999; 19: 9635-9641
        • Holahan M.R.
        • White N.M.
        Amygdala inactivation blocks expression of conditioned memory modulation and the promotion of avoidance and freezing.
        Behav Neurosci. 2004; 118: 24-35
        • Rorick-Kehn L.M.
        • Steinmetz J.E.
        Amygdalar unit activity during three learning tasks: Eyeblink classical conditioning, Pavlovian fear conditioning, and signaled avoidance conditioning.
        Behav Neurosci. 2005; 119: 1254-1273
        • Brush F.R.
        On the difference between animals that learn and do not learn to avoid electric shock.
        Psychon Sci. 1966; 5: 123-124
        • Brush F.R.
        Selection for differences in avoidance learning: The Syracuse strains differ in anxiety, not learning ability.
        Behav Genet. 2003; 33: 677-696
        • Bolles R.C.
        • Popp Jr, R.J.
        Parameters affecting the acquisition of Sidman avoidance.
        J Exp Anal Behav. 1964; 7: 315-321
        • Choi J.
        • LeDoux J.E.
        Lesions of the lateral/basal but not the central nucleus of the amygdala impair post-training performance of fear-induced 2-way active avoidance signaled by a conditioned stimulus: Program Number 623.5.
        Abstract Viewer/Itinerary Planner. Society for Neuroscience, Washington, DC2003 (Accessed January 7, 2010)
        • Schwartzbaum J.S.
        • Green R.H.
        • Beatty W.W.
        • Thompson J.B.
        Acquisition of avoidance behavior following septal lesions in the rats.
        J Comp Physiol Psychol. 1967; 63: 95-104
        • Blanchard R.J.
        • Blanchard D.C.
        Reactive and active reactions to fear-eliciting stimuli.
        J Comp Physiol Psychol. 1969; 68: 129-135
        • Blanchard R.J.
        • Blanchard D.C.
        • Fial R.A.
        Hippocampal lesions in rats and their effect on activity, avoidance, and aggression.
        J Comp Physiol Psychol. 1970; 71: 92-102
        • Anisman H.
        • Waller T.G.
        Facilitative and disruptive effects of prior exposure to shock on subsequent avoidance performance.
        J Comp Physiol Psychol. 1972; 78: 113-122
        • Overmier J.B.
        • Seligman M.E.
        Effects of inescapable shock upon subsequent escape and avoidance responding.
        J Comp Physiol Psychol. 1967; 63: 28-33
        • Overmier J.B.
        Interference with avoidance behavior: Failure to escape traumatic shock.
        J Exp Psychol. 1968; 78: 340-343
        • Bignami G.
        Selection for high rates and low rates of avoidance conditioning in the rat.
        Anim Behav. 1965; 13: 221-227
        • Brush F.R.
        • Froehlich J.C.
        • Sakellaris P.C.
        Genetic selection for avoidance behavior in the rat.
        Behav Genet. 1979; 9: 309-316
        • Ryzhova L. Iu
        • Kulagin D.A.
        • Lopatina N.G.
        Correlated variability in motor activity and emotionality in selecting rats for high and low values of active avoidance conditioned reflexes.
        Genetika. 1983; 19: 121-125
        • Blizard D.A.
        • Adams N.
        The Maudsley reactive and nonreactive strains: A new perspective.
        Behav Genet. 2002; 32: 277-299
        • Servatius R.J.
        • Jiao X.
        • Beck K.D.
        • Pang K.C.
        • Minor T.R.
        Rapid avoidance acquisition in Wistar-Kyoto rats.
        Behav Brain Res. 2008; 192: 191-197
        • Sidman M.
        Avoidance conditioning with brief shock and no exteroceptive warning signal.
        Science. 1953; 118: 157-158
        • Sidman M.
        Two temporal parameters of the maintenance of avoidance behavior by the white rat.
        J Comput Physiol Pshycol. 1953; 46: 253-261
        • Paxinos G.
        • Watson C.
        The Rat Brain in Stereotaxic Coordinates.
        5th ed. Elsevier/Academic Press, San Diego2005
        • Blanchard R.J.
        • Blanchard D.C.
        Crouching as an index of fear.
        J Comp Physiol Psychol. 1969; 67: 370-375
        • King F.A.
        Effects of septal and amygdaloid lesions on emotional behavior and conditioned avoidance responses in the rat.
        J Nerv Ment Dis. 1958; 126: 57-63
        • Grossman S.P.
        • Grossman L.
        • Walsh L.
        Functional organization of the rat amygdala with respect to avoidance behavior.
        J Comp Physiol Psychol. 1975; 88: 829-850
        • Roozendaal B.
        • Koolhaas J.M.
        • Bohus B.
        The central amygala is involved in conditioning but not retention of active and reactive shock avoidance in male rats.
        Behav Neural Biol. 1993; 59: 143-149
        • Isaacson R.L.
        • Douglas R.J.
        • Moore R.Y.
        The effect of radical hippocampal ablation on acquisition of avoidance response.
        J Comp Physiol Psychol. 1961; 54: 625-628
        • Cain C.K.
        • LeDoux J.E.
        Emotional processing and motivation: In search of brain mechanisms.
        in: Elliot A.J. Handbook of Approach and Avoidance Motivation. Psychology Press, Taylor and Francis Group, New York2008: 17-34
        • Balleine B.W.
        • Killcross S.
        Parallel incentive processing: An integrated view of amygdala function.
        Trends Neurosci. 2006; 39: 272-279
        • Zimmerman J.M.
        • Rabinak C.A.
        • McLachlan I.G.
        • Maren S.
        The central nucleus of the amygdala is essential for acquiring and expressing conditional fear after overtraining.
        Learn Mem. 2007; 14: 634-644
        • Poulus A.M.
        • Li V.
        • Sterlace S.S.
        • Tokushige F.
        • Ponnusamy R.
        • Fanselow M.S.
        Persistence of fear memory across time requires the basolateral amygdala complex.
        Proc Natl Acad Sci USA. 2009; 106: 11737-11741
        • Krieckhaus E.E.
        • Simmons H.J.
        • Thomas G.J.
        • Kenyon J.
        Septal lesions enhance shock avoidance behavior in the rat.
        Exp Neurol. 1964; 9: 107-113
        • de Oca B.M.
        • Minor T.R.
        • Fanselow M.S.
        Brief flight to a familiar enclosure in response to a conditional stimulus in rats.
        J Gen Psychol. 2007; 134: 153-172
        • Davis M.
        • Shi C.
        The extended amygdala: Are the central nucleus of the amygdala and the bed nucleus of the stria terminalis differentially involved in fear versus anxiety?.
        Ann N Y Acad Sci. 1999; 877: 281-291
        • Pitkänen A.
        Connectivity of the rat amygdaloid complex.
        in: Aggleton J.P. The Amygdala. Oxford University Press, Oxford, UK2000: 31-116
        • Sullivan G.M.
        • Apergis J.
        • Bush D.E.
        • Johnson L.R.
        • Hou M.
        • LeDoux J.E.
        Lesions of the bed nucleus of the stria terminalis disrupt corticosterone and freezing responses elicited by a contextual but not by a specific cue-conditioned fear stimulus.
        Neuroscience. 2004; 128: 7-14
        • LeDoux J.E.
        • Iwata J.
        • Cicchetti P.
        • Reis D.J.
        Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear.
        J Neurosci. 1988; 8: 2517-2529
        • Kim J.J.
        • Rison R.A.
        • Fanselow M.S.
        Effects of amygdala, hippocampus, and periaqueductal gray lesions on short- and long-term contextual fear.
        Behav Neurosci. 1993; 107: 1093-1098
        • Amorapanth P.
        • Nader K.
        • LeDoux J.E.
        Lesions of periaqueductal gray dissociate-conditioned freezing from conditioned suppression behavior in rats.
        Learn Mem. 1999; 6: 491-499
        • Jallestad F.K.
        • Markowska A.
        • Bakke H.K.
        Behavioral effects after ibotenic acid, 6- OHDA and electrolytic lesions in the central amygdala nucleus of the rat.
        Physiol Behav. 1986; 37: 855-862
        • Werka T.
        • Zielinski K.
        CS modality transfer of two-way avoidance in rats with central and basolateral amygdala lesions.
        Behav Brain Res. 1998; 93: 11-24
        • Kessler R.C.
        • Heeringa S.
        • Lakoma M.D.
        • Petukhova M.
        • Rupp A.E.
        • Schoenbaum M.
        • et al.
        The individual-level and societal-level effects of mental disorders on earnings in the United States: Results from the national comorbidity survey replication.
        Am J Psychiatry. 2008; 165: 703-711
        • Cloitre M.
        Effective psychotherapies for posttraumatic stress disorder: A review and critique.
        CNS Spectr. 2009; 14: 32-43
        • Kamin L.J.
        • Brimer C.J.
        • Black A.H.
        Conditioned suppression as a monitor of fear of the CS during the course of avoidance training.
        J Comp Physiological Psychology. 1962; 56: 497-501
        • Stovall-McClough K.C.
        • Cloitre M.
        Unresolved attachment, PTSD, and dissociation in women with childhood abuse histories.
        J Consult Clin Psychol. 2006; 74: 219-228

      Linked Article

      • Amygdala Activity, Fear, and Anxiety: Modulation by Stress
        Biological PsychiatryVol. 67Issue 12
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          Over the past approximately 30 years, the neuroscience community has made terrific strides in its understanding of the small region in the temporal lobe named for its peculiar almond shape, the amygdala. This area now provides among the best examples of how neural circuits control specific behaviors. In terms of our depth of understanding of its afferent and efferent connections, the role of incoming signals in modulating emotion-related behavior, and the functional and anatomic results of its projection patterns, the detailed understanding of the amygdala is unsurpassed.
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