Molecular Mechanisms of Memory Retrieval

Memory retrieval is a fundamental component or stage of memory processing. In fact, retrieval is the only possible measure of memory. The ability to recall past events is a major determinant of survival strategies in all species and is of paramount importance in determining our uniqueness as individuals. Most biological studies of memory using brain lesion and/or gene manipulation techniques cannot distinguish between effects on the molecular mechanisms of the encoding or consolidation of memories and those responsible for their retrieval from storage. Here we examine recent findings indicating the major molecular steps involved in memory retrieval in selected brain regions of the mammalian brain. Together the findings strongly suggest that memory formation and retrieval may share some molecular mechanisms in the hippocampus and that retrieval initiates extinction requiring activation of several signaling cascades and protein synthesis.

[1]  I. Izquierdo,et al.  B-50/GAP-43 Phosphorylation and PKC Activity are Increased in Rat Hippocampal Synaptosomal Membranes After an Inhibitory Avoidance Training , 1997, Neurochemical Research.

[2]  James L. McGaugh,et al.  Stress and glucocorticoids impair retrieval of long-term spatial memory , 1998, Nature.

[3]  M. Moser,et al.  Distributed Encoding and Retrieval of Spatial Memory in the Hippocampus , 1998, The Journal of Neuroscience.

[4]  I. Izquierdo,et al.  Involvement of hippocampal PKCβI isoform in the early phase of memory formation of an inhibitory avoidance learning , 2000, Brain Research.

[5]  J. David Sweatt,et al.  The MAPK cascade is required for mammalian associative learning , 1998, Nature Neuroscience.

[6]  Michael Davis,et al.  Mitogen-Activated Protein Kinase Cascade in the Basolateral Nucleus of Amygdala Is Involved in Extinction of Fear-Potentiated Startle , 2001, The Journal of Neuroscience.

[7]  I. Izquierdo,et al.  Neurotransmitter receptors involved in post-training memory processing by the amygdala, medial septum, and hippocampus of the rat. , 1992, Behavioral and neural biology.

[8]  I. Izquierdo,et al.  Participation of hippocampal metabotropic glutamate receptors, protein kinase A and mitogen-activated protein kinases in memory retrieval , 2000, Neuroscience.

[9]  M E Greenberg,et al.  Calcium signaling in neurons: molecular mechanisms and cellular consequences. , 1995, Science.

[10]  J. D. McGaugh,et al.  The contribution of pharmacology to research on the mechanisms of memory formation. , 2000, Trends in pharmacological sciences.

[11]  J. D. McGaugh,et al.  Basolateral Amygdala–Nucleus Accumbens Interactions in Mediating Glucocorticoid Enhancement of Memory Consolidation , 2001, The Journal of Neuroscience.

[12]  S. Tonegawa,et al.  The Essential Role of Hippocampal CA1 NMDA Receptor–Dependent Synaptic Plasticity in Spatial Memory , 1996, Cell.

[13]  James L McGaugh,et al.  The role of NMDA glutamate receptors, PKA, MAPK, and CAMKII in the hippocampus in extinction of conditioned fear , 2003, Hippocampus.

[14]  I. Izquierdo,et al.  Systemic Administration of ACTH or Vasopressin Reverses the Amnestic Effect of Posttraining β-Endorphin or Electroconvulsive Shock but Not That of Intrahippocampal Infusion of Protein Kinase Inhibitors , 1997, Neurobiology of Learning and Memory.

[15]  I. Izquierdo,et al.  Pharmacological demonstration of the differential involvement of protein kinase C isoforms in short- and long-term memory formation and retrieval of one-trial avoidance in rats , 2000, Psychopharmacology.

[16]  M. Koch,et al.  The metabotropic glutamate receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) blocks fear conditioning in rats , 2001, Neuropharmacology.

[17]  I. Izquierdo,et al.  Molecular signalling pathways in the cerebral cortex are required for retrieval of one-trial avoidance learning in rats , 2000, Behavioural Brain Research.

[18]  K L Thomas,et al.  Fear memory retrieval induces CREB phosphorylation and Fos expression within the amygdala , 2001, The European journal of neuroscience.

[19]  I Izquierdo,et al.  Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[20]  D. Riccio,et al.  ACTH produces long-lasting recovery following partial extinction of an active avoidance response. , 1989, Behavioral and neural biology.

[21]  J. D. McGaugh,et al.  Picrotoxin enhances latent extinction of conditioned fear. , 1990, Behavioral neuroscience.

[22]  I. Izquierdo,et al.  Simultaneous modulation of retrieval by dopaminergic D1, β-noradrenergic, serotonergic-1A and cholinergic muscarinic receptors in cortical structures of the rat , 2001, Behavioural Brain Research.

[23]  L R Squire,et al.  Relationship between magnitude of damage to the hippocampus and impaired recognition memory in monkeys , 2001, Hippocampus.

[24]  G. Lynch,et al.  Antagonism of NMDA receptors impairs acquisition but not retention of olfactory memory. , 1989, Behavioral neuroscience.

[25]  I. Izquierdo,et al.  Learning-associated activation of nuclear MAPK, CREB and Elk-1, along with Fos production, in the rat hippocampus after a one-trial avoidance learning: abolition by NMDA receptor blockade. , 2000, Brain research. Molecular brain research.

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

[27]  Larry R. Squire,et al.  Memory for places learned long ago is intact after hippocampal damage , 1999, Nature.

[28]  S. J. Martin,et al.  Reversible neural inactivation reveals hippocampal participation in several memory processes , 1999, Nature Neuroscience.

[29]  I. Izquierdo,et al.  Correlation between the Pharmacology of Long-Term Potentiation and the Pharmacology of Memory , 1995, Neurobiology of Learning and Memory.

[30]  I. Izquierdo,et al.  Short- and Long-Term Memory Are Differentially Affected by Metabolic Inhibitors Given into Hippocampus and Entorhinal Cortex , 2000, Neurobiology of Learning and Memory.

[31]  Stephen Maren,et al.  Hippocampal Inactivation Disrupts Contextual Retrieval of Fear Memory after Extinction , 2001, The Journal of Neuroscience.

[32]  J L McGaugh,et al.  Antisense oligodeoxynucleotide-mediated disruption of hippocampal cAMP response element binding protein levels impairs consolidation of memory for water maze training. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[33]  I. Izquierdo,et al.  Two different properties of short- and long-term memory , 1999, Behavioural Brain Research.

[34]  Y. Dudai,et al.  Memory Extinction, Learning Anew, and Learning the New: Dissociations in the Molecular Machinery of Learning in Cortex , 2001, Science.

[35]  J. D. McGaugh.  Memory--a century of consolidation. , 2000, Science.

[36]  J. D. McGaugh,et al.  Effect of a novel experience prior to training or testing on retention of an inhibitory avoidance response in mice: involvement of an opioid system. , 1985, Behavioral and neural biology.

[37]  D. Amaral,et al.  Three Cases of Enduring Memory Impairment after Bilateral Damage Limited to the Hippocampal Formation , 1996, The Journal of Neuroscience.

[38]  M. Bear,et al.  A molecular correlate of memory and amnesia in the hippocampus , 1999, Nature Neuroscience.

[39]  J L McGaugh,et al.  Time-Dependent Processes in Memory Storage , 1966, Science.

[40]  T. Abel,et al.  Different Requirements for Protein Synthesis in Acquisition and Extinction of Spatial Preferences and Context-Evoked Fear , 2001, The Journal of Neuroscience.

[41]  J. Konorski.  Conditioned reflexes and neuron organization. , 1948 .

[42]  Stephen Maren,et al.  Contextual and auditory fear conditioning are mediated by the lateral, basal, and central amygdaloid nuclei in rats. , 2001, Learning & memory.

[43]  J. D. McGaugh,et al.  Involvement of a basolateral amygdala complex–nucleus accumbens pathway in glucocorticoid‐induced modulation of memory consolidation , 2000, The European journal of neuroscience.

[44]  Tobias Bonhoeffer,et al.  Essential Role for TrkB Receptors in Hippocampus-Mediated Learning , 1999, Neuron.

[45]  S. J. Martin,et al.  Synaptic plasticity and memory: an evaluation of the hypothesis. , 2000, Annual review of neuroscience.

[46]  Alcino J. Silva,et al.  Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein , 1994, Cell.

[47]  I. Izquierdo.  Different forms of post-training memory processing. , 1989, Behavioral and neural biology.

[48]  L. Squire,et al.  The primate hippocampal formation: evidence for a time-limited role in memory storage. , 1990, Science.

[49]  J. Sweatt,et al.  A role for the beta isoform of protein kinase C in fear conditioning. , 2000, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[50]  Aryeh Routtenberg,et al.  GAP-43: an intrinsic determinant of neuronal development and plasticity , 1997, Trends in Neurosciences.

[51]  L R Squire,et al.  Neuroscience: breaking down scientific barriers to the study of brain and mind. , 2006, Science.

[52]  Joseph E LeDoux,et al.  The Amygdala Modulates Memory Consolidation of Fear-Motivated Inhibitory Avoidance Learning But Not Classical Fear Conditioning , 2000, The Journal of Neuroscience.

[53]  I. Izquierdo,et al.  Novelty enhances retrieval: molecular mechanisms involved in rat hippocampus , 2001, The European journal of neuroscience.

[54]  D. Riccio,et al.  The status of memory following experimentally induced amnesias: Gone, but not forgotten , 1984 .

[55]  D. Storm,et al.  Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning , 1998, Nature Neuroscience.

[56]  J. D. McGaugh,et al.  Retrieval of memory for fear-motivated training initiates extinction requiring protein synthesis in the rat hippocampus , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[57]  P. E. Gold.  The use of avoidance training in studies of modulation of memory storage. , 1986, Behavioral and neural biology.

[58]  J. D. McGaugh,et al.  Glucocorticoid enhancement of memory consolidation in the rat is blocked by muscarinic receptor antagonism in the basolateral amygdala , 2000, The European journal of neuroscience.

[59]  Alcino J. Silva,et al.  Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice. , 1992, Science.

[60]  E. Kandel.  The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses , 2001, Science.

[61]  Michael Davis,et al.  Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[62]  Edwin J. Weeber,et al.  A Role for the β Isoform of Protein Kinase C in Fear Conditioning , 2000, The Journal of Neuroscience.

[63]  I. Izquierdo,et al.  Differential Role of Hippocampal cAMP-Dependent Protein Kinase in Short- and Long-Term Memory , 2000, Neurochemical Research.

[64]  R. Morris,et al.  Delay‐dependent impairment of a matching‐to‐place task with chronic and intrahippocampal infusion of the NMDA‐antagonist D‐AP5 , 1999, Hippocampus.

[65]  T. Tully,et al.  CREB and the formation of long-term memory , 1996, Current Opinion in Neurobiology.

[66]  Stephen Maren,et al.  Muscimol Inactivation of the Dorsal Hippocampus Impairs Contextual Retrieval of Fear Memory , 1999, The Journal of Neuroscience.

[67]  I. Izquierdo,et al.  Memory Formation: The Sequence of Biochemical Events in the Hippocampus and Its Connection to Activity in Other Brain Structures , 1997, Neurobiology of Learning and Memory.