Neurophysiological theory of kamin blocking in fear conditioning.

Kamin blocking in fear conditioning is thought to reflect diminished processing of the unconditional stimulus (US) in the presence of a conditional stimulus (CS-super(+)) that was previously paired with this US. According to Fanselow's (1998) hypothesis, the CS-super(+) drives output from the amygdala that ultimately produces analgesia by causing opiate release onto afferent pain circuits. This hypothesis was explored quantitatively through neurophysiological simulations. The results suggest that opiate-mediated, negative-feedback control of US processing is too slow for efficient blocking of cue conditioning. The reason is that conditioning-produced synaptic modifications can be induced before the opiate-mediated inhibition has any substantial effect on US processing. The results suggest the existence of an additional, faster-acting, inhibitory neurotransmitter in the blocking circuit.

[1]  Joseph E LeDoux Emotion Circuits in the Brain , 2000 .

[2]  G. McNally,et al.  The midbrain periaqueductal gray and fear extinction: opioid receptor subtype and roles of cyclic AMP, protein kinase A, and mitogen-activated protein kinase. , 2005, Behavioral neuroscience.

[3]  J J Kim,et al.  Amygdalar NMDA Receptors Are Critical for the Expression of Multiple Conditioned Fear Responses , 2001, The Journal of Neuroscience.

[4]  Joel L. Davis,et al.  Single neuron computation , 1992 .

[5]  E. Wasserman,et al.  Cue Competition in Causality Judgments: The Role of Nonpresentation of Compound Stimulus Elements , 1994 .

[6]  E. W. Kairiss,et al.  Hebbian synapses: biophysical mechanisms and algorithms. , 1990, Annual review of neuroscience.

[7]  R. Rescorla,et al.  A theory of Pavlovian conditioning : Variations in the effectiveness of reinforcement and nonreinforcement , 1972 .

[8]  Javier F. Medina,et al.  Timing Mechanisms in the Cerebellum: Testing Predictions of a Large-Scale Computer Simulation , 2000, The Journal of Neuroscience.

[9]  A. Dickinson,et al.  Within Compound Associations Mediate the Retrospective Revaluation of Causality Judgements , 1996, The Quarterly journal of experimental psychology. B, Comparative and physiological psychology.

[10]  S. Kelso,et al.  Hebbian synapses in hippocampus. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[11]  M L Hines,et al.  Neuron: A Tool for Neuroscientists , 2001, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[12]  G. Bower,et al.  From conditioning to category learning: an adaptive network model. , 1988 .

[13]  Gavan P McNally,et al.  Blocking, unblocking, and overexpectation of fear: a role for opioid receptors in the regulation of Pavlovian association formation. , 2004, Behavioral neuroscience.

[14]  T. H. Brown,et al.  Voltage-clamp analysis of mossy fiber synaptic input to hippocampal neurons. , 1983, Journal of neurophysiology.

[15]  W. Schultz,et al.  Dopamine responses comply with basic assumptions of formal learning theory , 2001, Nature.

[16]  T. H. Brown,et al.  Dendritic spines: convergence of theory and experiment. , 1992, Science.

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

[18]  S. Maier,et al.  The nature of conditioned anti-analgesia: spinal cord opiate and anti-opiate neurochemistry , 1994, Brain Research.

[19]  T. H. Brown,et al.  Giant synaptic potential hypothesis for epileptiform activity. , 1981, Science.

[20]  A. Delgado-Escueta,et al.  Basic mechanisms of the epilepsies : molecular and cellular approaches , 1986 .

[21]  Richard F. Thompson,et al.  Neural substrates of eyeblink conditioning: acquisition and retention. , 2003, Learning & memory.

[22]  P. Bellgowan,et al.  Inhibition of the tail flick reflex following microinjection of morphine into the amygdala. , 1993, NeuroReport.

[23]  A. Siegel Stimulus generalization of a classically conditioned response along a temporal dimension. , 1967, Journal of comparative and physiological psychology.

[24]  Elan D. Louis,et al.  Merritt's Neurology , 2001 .

[25]  R. Rescorla Reduction in the effectiveness of reinforcement after prior excitatory conditioning , 1970 .

[26]  P. Holland,et al.  Amygdala–frontal interactions and reward expectancy , 2004, Current Opinion in Neurobiology.

[27]  M. Davis,et al.  Temporal specificity of fear conditioning: effects of different conditioned stimulus-unconditioned stimulus intervals on the fear-potentiated startle effect. , 1989, Journal of experimental psychology. Animal behavior processes.

[28]  T. H. Brown,et al.  Central Amygdala Lesions Block Ultrasonic Vocalization and Freezing as Conditional But Not Unconditional Responses , 2003, The Journal of Neuroscience.

[29]  P. Holland,et al.  Basal forebrain cholinergic lesions disrupt increments but not decrements in conditioned stimulus processing , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  Jennifer A. Hobin,et al.  Context-Dependent Neuronal Activity in the Lateral Amygdala Represents Fear Memories after Extinction , 2003, The Journal of Neuroscience.

[31]  Mechanism for Temporal Encoding in Fear Conditioning , 1997 .

[32]  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.

[33]  J. E. Mazur,et al.  Evaluation of Blocking and Conditioned Inhibition to a CS Signaling a Decrease in US Intensity , 1980 .

[34]  R. Zucker,et al.  Release of Neurotransmitters , 2004 .

[35]  Ja Wook Koo,et al.  Behavioral / Systems / Cognitive Selective Neurotoxic Lesions of Basolateral and Central Nuclei of the Amygdala Produce Differential Effects on Fear Conditioning , 2004 .

[36]  E. Kremer Effect of posttrial episodes on conditioning in compound conditioned stimuli. , 1979, Journal of experimental psychology. Animal behavior processes.

[37]  M. Gallagher,et al.  Blocking can occur without losses in attention in rats with selective removal of hippocampal cholinergic input. , 1999, Behavioral neuroscience.

[38]  M. Gabriel,et al.  Neuronal encoding of conditional stimulus duration in the cingulate cortex and the limbic thalamus of rabbits. , 1990, Behavioral neuroscience.

[39]  Joseph E LeDoux,et al.  New vistas on amygdala networks in conditioned fear. , 2004, Journal of neurophysiology.

[40]  M. Fanselow,et al.  Pavlovian Conditioning, Negative Feedback, and Blocking: Mechanisms that Regulate Association Formation , 1998, Neuron.

[41]  Derick H. Lindquist,et al.  Amygdalar NMDA receptors control the expression of associative reflex facilitation and three other conditional responses. , 2004, Behavioral neuroscience.

[42]  Richard S. Sutton,et al.  Reinforcement Learning: An Introduction , 1998, IEEE Trans. Neural Networks.

[43]  M. Fanselow Conditioned Fear‐Induced Opiate Analgesia: A Competing Motivational State Theory of Stress Analgesia a , 1986, Annals of the New York Academy of Sciences.

[44]  A. C. Greenwood,et al.  Quantal mechanism of long-term potentiation in hippocampal mossy-fiber synapses. , 1994, Journal of neurophysiology.

[45]  Anthony M. Zador,et al.  Computational models of hippocampal neurons , 1992 .

[46]  Javier F. Medina,et al.  Computer simulation of cerebellar information processing , 2000, Nature Neuroscience.

[47]  R. Hinson Effects of UCS preexposure on excitatory and inhibitory rabbit eyelid conditioning: an associative effect of conditioned contextual stimuli. , 1982, Journal of experimental psychology. Animal behavior processes.

[48]  Joseph E LeDoux,et al.  Fear Conditioning Enhances Different Temporal Components of Tone-Evoked Spike Trains in Auditory Cortex and Lateral Amygdala , 1997, Neuron.

[49]  W. Schultz,et al.  Coding of Predicted Reward Omission by Dopamine Neurons in a Conditioned Inhibition Paradigm , 2003, The Journal of Neuroscience.

[50]  S. Nelson,et al.  Homeostatic plasticity in the developing nervous system , 2004, Nature Reviews Neuroscience.

[51]  P. Shinnick‐Gallagher,et al.  The central nucleus of the rat amygdala: in vitro intracellular recordings , 1993, Brain Research.

[52]  F. Helmstetter,et al.  The amygdala is essential for the expression of conditional hypoalgesia. , 1992, Behavioral neuroscience.

[53]  N. Schmajuk,et al.  Latent inhibition: a neural network approach. , 1996, Journal of experimental psychology. Animal behavior processes.

[54]  H. Fields,et al.  Direct and indirect actions of morphine on medullary neurons that modulate nociception , 1992, Neuroscience.

[55]  T. H. Brown,et al.  Fear conditioning model predicts key temporal aspects of conditioned response production , 2000, Psychobiology.

[56]  R. Sutton,et al.  Simulation of anticipatory responses in classical conditioning by a neuron-like adaptive element , 1982, Behavioural Brain Research.

[57]  D. Bruce,et al.  Fifty Years Since Lashley's In Search of the Engram: Refutations and Conjectures , 2001, Journal of the history of the neurosciences.

[58]  E. Bullmore,et al.  Society for Neuroscience Abstracts , 1997 .

[59]  F. Helmstetter,et al.  Conditional hypoalgesia is attenuated by Naltrexone applied to the periaqueductal gray , 1990, Brain Research.

[60]  M. Fendt,et al.  The neuroanatomical and neurochemical basis of conditioned fear , 1999, Neuroscience & Biobehavioral Reviews.

[61]  A. Light,et al.  Spinal laminae I-II neurons in rat recorded in vivo in whole cell, tight seal configuration: properties and opioid responses. , 1999, Journal of neurophysiology.

[62]  Joseph E LeDoux,et al.  NMDA Receptors and L-Type Voltage-Gated Calcium Channels Contribute to Long-Term Potentiation and Different Components of Fear Memory Formation in the Lateral Amygdala , 2002, The Journal of Neuroscience.

[63]  W. Zieglgänsberger,et al.  The effects of methionine- and leucine-enkephalin on spinal neurones of the cat , 1979, Brain Research.

[64]  T. H. Brown,et al.  Perirhinal-amygdala circuit-level computational model of temporal encoding in fear conditioning , 1999, Psychobiology.

[65]  P. Bellgowan,et al.  Effects of muscimol applied to the basolateral amygdala on acquisition and expression of contextual fear conditioning in rats. , 1994, Behavioral neuroscience.

[66]  Derick H. Lindquist,et al.  Amygdala lesions block conditioned enhancement of the early component of the rat eyeblink reflex. , 2001, Behavioral neuroscience.

[67]  T. H. Brown,et al.  Predominance of Late-Spiking Neurons in Layer VI of Rat Perirhinal Cortex , 2001, The Journal of Neuroscience.

[68]  P. Holland,et al.  Amygdala circuitry in attentional and representational processes , 1999, Trends in Cognitive Sciences.

[69]  S. Klein,et al.  Pavlovian conditioning and the status of traditional learning theory , 1991 .

[70]  John M. Beggs,et al.  Prolonged synaptic integration in perirhinal cortical neurons. , 2000, Journal of neurophysiology.

[71]  Eric L. Schwartz,et al.  Computational Neuroscience , 1993, Neuromethods.

[72]  J. Jack,et al.  Electric current flow in excitable cells , 1975 .

[73]  G. Quirk,et al.  Neuronal signalling of fear memory , 2004, Nature Reviews Neuroscience.

[74]  M. Schiess,et al.  Characterization of the electrophysiological and morphological properties of rat central amygdala neurons in vitro , 1999, Journal of neuroscience research.

[75]  J. Pearce,et al.  A model for Pavlovian learning: Variations in the effectiveness of conditioned but not of unconditioned stimuli. , 1980 .

[76]  R M Church,et al.  Scalar Timing in Memory , 1984, Annals of the New York Academy of Sciences.

[77]  A. Dickinson,et al.  Neuronal coding of prediction errors. , 2000, Annual review of neuroscience.

[78]  A G Barto,et al.  Toward a modern theory of adaptive networks: expectation and prediction. , 1981, Psychological review.

[79]  T. Imig,et al.  Modification of unit discharges in the medial geniculate nucleus by click-shock pairing. , 1972, Experimental neurology.

[80]  James A. Anderson,et al.  An Introduction To Neural Networks , 1998 .

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

[82]  Patrick R. Hof,et al.  Cellular and molecular neuroscience , 1999 .

[83]  R. F. Thompson,et al.  The search for the engram. , 1976, The American psychologist.

[84]  Anthony M. Zador,et al.  Self-organization of Hebbian Synapses in Hippocampal Neurons , 1990, NIPS.

[85]  George Adelman,et al.  Encyclopedia of neuroscience , 2004 .

[86]  T. Otto,et al.  Neural substrates of olfactory discrimination learning with auditory secondary reinforcement. I. Contributions of the basolateral amygdaloid complex and orbitofrontal cortex , 2003, Integrative physiological and behavioral science : the official journal of the Pavlovian Society.

[87]  Andrew M. Poulos,et al.  The neuroscience of mammalian associative learning. , 2005, Annual review of psychology.

[88]  Richard F. Thompson,et al.  Modeling the Neural Substrates of Associative Learning and Memory: A Computational Approach , 1987 .

[89]  R. D. Traub,et al.  Models of the cellular mechanism underlying propagation of epileptiform activity in the CA2-CA3 region of the hippocampal slice , 1987, Neuroscience.

[90]  J. H. Neely,et al.  Attenuation of blocking with shifts in reward: The involvement of schedule-generated contextual cues , 1974 .

[91]  T. H. Brown,et al.  Biophysical model of a Hebbian synapse. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[92]  J. Pearce,et al.  Latent inhibition of a CS during CS-US pairings. , 1979, Journal of experimental psychology. Animal behavior processes.

[93]  G. McNally,et al.  Opioid Receptors in the Midbrain Periaqueductal Gray Regulate Extinction of Pavlovian Fear Conditioning , 2004, The Journal of Neuroscience.

[94]  J. Power,et al.  The amygdaloid complex: anatomy and physiology. , 2003, Physiological reviews.

[95]  N. Mackintosh,et al.  Surprise and the attenuation of blocking. , 1976 .

[96]  Thomas H. Brown,et al.  Patch-Clamp Techniques Applied To Brain Slices , 2002 .

[97]  D. Paré,et al.  Stimulation of Medial Prefrontal Cortex Decreases the Responsiveness of Central Amygdala Output Neurons , 2003, The Journal of Neuroscience.

[98]  Joseph E LeDoux,et al.  Parallels between cerebellum- and amygdala-dependent conditioning , 2002, Nature Reviews Neuroscience.

[99]  Richard Durbin,et al.  The computing neuron , 1989 .

[100]  Richard F. Thompson In search of memory traces. , 2005, Annual review of psychology.

[101]  N. Weinberger,et al.  Modification of auditory and somatosensory system activity during pupillary conditioning in the paralyzed cat. , 1975, Journal of neurophysiology.

[102]  A. R. Wagner,et al.  Evolution of a structured connectionist model of Pavlovian conditioning (AESOP). , 1989 .

[103]  D. Johnston,et al.  Foundations of Cellular Neurophysiology , 1994 .

[104]  Ralph R. Miller,et al.  Information processing in animals : memory mechanisms , 1983 .

[105]  Katsuhiko Ogata,et al.  Modern Control Engineering , 1970 .

[106]  E. Kremer The Rescorla-Wagner model: losses in associative strength in compound conditioned stimuli. , 1978, Journal of experimental psychology. Animal behavior processes.

[107]  N. Donegan,et al.  Some Relationships Between a Computational Model (Sop) and a Neural Circuit for Pavlovian (Rabbit Eyeblink) Conditioning , 1989 .

[108]  M. Fanselow,et al.  Temporally Graded Retrograde Amnesia of Contextual Fear after Hippocampal Damage in Rats: Within-Subjects Examination , 1999, The Journal of Neuroscience.

[109]  Ian P. L. McLaren,et al.  The computational unit as an assembly of neurones: an implementation of an error correcting learning algorithm , 1989 .

[110]  P. Bellgowan,et al.  Lesions of the amygdala block conditional hypoalgesia on the tail flick test , 1993, Brain Research.

[111]  Joseph E LeDoux,et al.  Reply — reconsolidation: The labile nature of consolidation theory , 2000, Nature Reviews Neuroscience.

[112]  T. H. Brown,et al.  Temporal encoding in fear conditioning revealed through associative reflex facilitation. , 2004 .

[113]  R. Bolles,et al.  Clinical implications of Bolles & Fanselow's pain/fear model , 1980, Behavioral and Brain Sciences.

[114]  Ralph R. Miller,et al.  Spontaneous recovery from forward and backward blocking. , 2005, Journal of experimental psychology. Animal behavior processes.

[115]  N. Mackintosh,et al.  Reinforcer specificity in the enhancement of conditioning by posttrial surprise. , 1979 .

[116]  D. Norman Learning and Memory , 1982 .

[117]  J. Gibbon,et al.  Timing and time perception. , 1984, Annals of the New York Academy of Sciences.

[118]  F. Helmstetter,et al.  Antinociception produced by mu opioid receptor activation in the amygdala is partly dependent on activation of mu opioid and neurotensin receptors in the ventral periaqueductal gray , 2000, Brain Research.

[119]  T. H. Brown,et al.  Morphology and physiology of neurons in the rat perirhinal‐lateral amygdala area , 1999, The Journal of comparative neurology.

[120]  E. Bienenstock,et al.  Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[121]  R. F. Thompson,et al.  Inhibitory cerebello-olivary projections and blocking effect in classical conditioning. , 1998, Science.

[122]  T. H. Brown,et al.  Three classes of pyramidal neurons in layer V of rat perirhinal cortex , 2002, Hippocampus.

[123]  T. H. Brown,et al.  Complex synaptic current waveforms evoked in hippocampal pyramidal neurons by extracellular stimulation of dentate gyrus. , 1998, Journal of neurophysiology.

[124]  Wolfgang Walz,et al.  Patch-clamp analysis : advanced techniques , 2002 .

[125]  D. A. Baxter,et al.  Quantal mechanism of long-term synaptic potentiation. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[126]  M. Fanselow,et al.  Associative regulation of Pavlovian fear conditioning: unconditional stimulus intensity, incentive shifts, and latent inhibition. , 1992, Journal of experimental psychology. Animal behavior processes.

[127]  D. Buonomano,et al.  The neural basis of temporal processing. , 2004, Annual review of neuroscience.

[128]  M. Fanselow Naloxone and Pavlovian fear conditioning , 1981 .

[129]  D. Jaffe,et al.  Passive normalization of synaptic integration influenced by dendritic architecture. , 1999, Journal of neurophysiology.

[130]  M Migliore,et al.  Computer simulations of morphologically reconstructed CA3 hippocampal neurons. , 1995, Journal of neurophysiology.

[131]  R K Wong,et al.  Cellular basis of neuronal synchrony in epilepsy. , 1986, Advances in neurology.

[132]  N. Mackintosh,et al.  Conditioning And Associative Learning , 1983 .

[133]  Blocking, unblocking, and overexpectation in autoshaping with pigeons. , 1996, Journal of the experimental analysis of behavior.