Searching for Engrams

Recent advances in cellular imaging technologies together with novel genetic tools have enabled the observation of minute anatomical changes in the intact brain. This has elevated the search for physical correlates of memory, one of the longstanding questions in modern neurobiology, to a new level. Utilizing these new tools, several studies have recently been published pointing to subcellular structural changes occurring when the brain stores information about the environment. While most of these studies still fall short of investigating memory as commonly defined in neuropsychological terms, they are paving the way to more refined experiments, which come closer to the identification of true "memory traces." In the not too distant future we will be able to observe physical changes that occur during learning in the intact animal in real time, leading the way to understanding these processes in unprecedented detail.

[1]  C. H. Bailey,et al.  Long-term memory in Aplysia modulates the total number of varicosities of single identified sensory neurons. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[2]  P Andersen,et al.  An increase in dendritic spine density on hippocampal CA1 pyramidal cells following spatial learning in adult rats suggests the formation of new synapses. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

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

[4]  G. Weissmann In Search of Memory: The Emergence Of a New Science of Mind. , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[5]  Y. Dan,et al.  Receptive-Field Modification in Rat Visual Cortex Induced by Paired Visual Stimulation and Single-Cell Spiking , 2006, Neuron.

[6]  M. Heisenberg,et al.  An engram found? Evaluating the evidence from fruit flies , 2004, Current Opinion in Neurobiology.

[7]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[8]  Y. Frégnac,et al.  A cellular analogue of visual cortical plasticity , 1988, Nature.

[9]  E. Kandel In search of memory : the emergence of a new science of mind , 2007 .

[10]  T. Wiesel,et al.  Receptive field dynamics in adult primary visual cortex , 1992, Nature.

[11]  M. Ahissar,et al.  Dependence of cortical plasticity on correlated activity of single neurons and on behavioral context. , 1992, Science.

[12]  C. Gilbert,et al.  Axonal sprouting accompanies functional reorganization in adult cat striate cortex , 1994, Nature.

[13]  P. Klopfer,et al.  The Foundations of Ethology , 1981 .

[14]  N. Kasthuri,et al.  Long-term dendritic spine stability in the adult cortex , 2002, Nature.

[15]  M. Chalfie,et al.  Green fluorescent protein as a marker for gene expression. , 1994, Science.

[16]  Kevan A. C. Martin,et al.  Protracted Synaptogenesis after Activity-Dependent Spinogenesis in Hippocampal Neurons , 2007, The Journal of Neuroscience.

[17]  M. Shermer,et al.  A new phrenology? , 2008, Scientific American.

[18]  D. Tank,et al.  Intracellular dynamics of hippocampal place cells during virtual navigation , 2009, Nature.

[19]  Richard Mooney,et al.  Rapid spine stabilization and synaptic enhancement at the onset of behavioural learning , 2010, Nature.

[20]  Gene E. Robinson,et al.  Experience- and Age-Related Outgrowth of Intrinsic Neurons in the Mushroom Bodies of the Adult Worker Honeybee , 2001, The Journal of Neuroscience.

[21]  K. Svoboda,et al.  Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex , 2002, Nature.

[22]  D. Hubel,et al.  Plasticity of ocular dominance columns in monkey striate cortex. , 1977, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[23]  J. Kaas,et al.  Large-scale sprouting of cortical connections after peripheral injury in adult macaque monkeys. , 1998, Science.

[24]  Tobias Bonhoeffer,et al.  Prior experience enhances plasticity in adult visual cortex , 2006, Nature Neuroscience.

[25]  Dirk Trauner,et al.  Engineering light-gated ion channels. , 2006, Biochemistry.

[26]  D. Hubel,et al.  SINGLE-CELL RESPONSES IN STRIATE CORTEX OF KITTENS DEPRIVED OF VISION IN ONE EYE. , 1963, Journal of neurophysiology.

[27]  David S. Greenberg,et al.  Visually evoked activity in cortical cells imaged in freely moving animals , 2009, Proceedings of the National Academy of Sciences.

[28]  Gabriel Horn,et al.  Pathways of the past: the imprint of memory , 2004, Nature Reviews Neuroscience.

[29]  Andrés Hurtado,et al.  Chronically CNS-Injured Adult Sensory Neurons Gain Regenerative Competence upon a Lesion of Their Peripheral Axon , 2009, Current Biology.

[30]  K. Svoboda,et al.  Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice , 2008, Nature.

[31]  L. Maffei,et al.  Molecular basis of plasticity in the visual cortex , 2003, Trends in Neurosciences.

[32]  M. Stryker,et al.  Delayed plasticity of inhibitory neurons in developing visual cortex , 2008, Proceedings of the National Academy of Sciences.

[33]  G. Feng,et al.  Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFP , 2000, Neuron.

[34]  C. H. Bailey,et al.  Time course of structural changes at identified sensory neuron synapses during long-term sensitization in Aplysia , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[35]  G. Feng,et al.  Dynamic Remodeling of Dendritic Arbors in GABAergic Interneurons of Adult Visual Cortex , 2005, PLoS biology.

[36]  E. Knudsen Instructed learning in the auditory localization pathway of the barn owl , 2002, Nature.

[37]  W. Gan,et al.  Stably maintained dendritic spines are associated with lifelong memories , 2009, Nature.

[38]  John Anderson The foundations of IN , 2002 .

[39]  Wei-Chung Allen Lee,et al.  A dynamic zone defines interneuron remodeling in the adult neocortex , 2008, Proceedings of the National Academy of Sciences.

[40]  Johan J. Bolhuis,et al.  Neural mechanisms of birdsong memory , 2006, Nature Reviews Neuroscience.

[41]  R. Reid,et al.  Homeostatic Regulation of Eye-Specific Responses in Visual Cortex during Ocular Dominance Plasticity , 2007, Neuron.

[42]  T. Bliss,et al.  The Hippocampus Book , 2006 .

[43]  L. Minichiello TrkB signalling pathways in LTP and learning , 2009, Nature Reviews Neuroscience.

[44]  Tobias Bonhoeffer,et al.  LTD Induction Causes Morphological Changes of Presynaptic Boutons and Reduces Their Contacts with Spines , 2008, Neuron.

[45]  E. Ahissar,et al.  A neuronal analogue of state-dependent learning , 2000, Nature.

[46]  Karel Svoboda,et al.  Experience-dependent and cell-type-specific spine growth in the neocortex , 2006, Nature.

[47]  Y. Miyashita,et al.  Neuronal correlate of pictorial short-term memory in the primate temporal cortexYasushi Miyashita , 1988, Nature.

[48]  E. Kandel,et al.  Target-dependent structural changes accompanying long-term synaptic facilitation in Aplysia neurons. , 1990, Science.

[49]  Yi Zuo,et al.  Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex , 2005, Nature.

[50]  T. Bonhoeffer,et al.  Experience leaves a lasting structural trace in cortical circuits , 2008, Nature.

[51]  A. Borst,et al.  Input Organization of Multifunctional Motion-Sensitive Neurons in the Blowfly , 2003, The Journal of Neuroscience.

[52]  R. Morris,et al.  Elements of a neurobiological theory of hippocampal function: the role of synaptic plasticity, synaptic tagging and schemas , 2006, The European journal of neuroscience.

[53]  K. Svoboda,et al.  Cell Type-Specific Structural Plasticity of Axonal Branches and Boutons in the Adult Neocortex , 2006, Neuron.

[54]  C. Schreiner,et al.  A synaptic memory trace for cortical receptive field plasticity , 2007, Nature.

[55]  F. Valverde,et al.  Apical dendritic spines of the visual cortex and light deprivation in the mouse , 2004, Experimental Brain Research.

[56]  E. Cocker,et al.  In vivo brain imaging using a portable 3.9 gram two-photon fluorescence microendoscope. , 2005, Optics letters.

[57]  Sooyoung Chung,et al.  Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex , 2005, Nature.

[58]  M. Cynader,et al.  Somatosensory cortical map changes following digit amputation in adult monkeys , 1984, The Journal of comparative neurology.

[59]  H. Ebbinghaus Uber das Gedachtnis , 1996 .

[60]  J. Knott The organization of behavior: A neuropsychological theory , 1951 .

[61]  K. Svoboda,et al.  Spine growth precedes synapse formation in the adult neocortex in vivo , 2006, Nature Neuroscience.

[62]  B. Hassenstein,et al.  Ommatidienraster und afferente Bewegungsintegration , 1951, Zeitschrift für vergleichende Physiologie.

[63]  Tracey J. Shors,et al.  Associative Memory Formation Increases the Observation of Dendritic Spines in the Hippocampus , 2003, The Journal of Neuroscience.

[64]  G. Shepherd,et al.  Transient and Persistent Dendritic Spines in the Neocortex In Vivo , 2005, Neuron.

[65]  R. Menzel,et al.  Learning and memory in honeybees: from behavior to neural substrates. , 1996, Annual review of neuroscience.

[66]  William T. Newsome,et al.  Cortical microstimulation influences perceptual judgements of motion direction , 1990, Nature.

[67]  Y. Dudai,et al.  Morphology of a sensory neuron in Drosophila is abnormal in memory mutants and changes during aging. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[68]  B L McNaughton,et al.  Dynamics of the hippocampal ensemble code for space. , 1993, Science.

[69]  C Pantev,et al.  Reorganizational and perceptional changes after amputation. , 1996, Brain : a journal of neurology.

[70]  D. Tank,et al.  Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice , 2007, Neuron.

[71]  Willie F. Tobin,et al.  Rapid formation and selective stabilization of synapses for enduring motor memories , 2009, Nature.

[72]  Feng Zhang,et al.  Multimodal fast optical interrogation of neural circuitry , 2007, Nature.

[73]  W. Denk,et al.  Two-photon laser scanning fluorescence microscopy. , 1990, Science.

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

[75]  Santiago Ramón y Cajal,et al.  Neue Darstellung vom histologischen Bau des Centralnervensystems , 1894 .

[76]  T. Bonhoeffer,et al.  Massive restructuring of neuronal circuits during functional reorganization of adult visual cortex , 2008, Nature Neuroscience.

[77]  J. Kaas,et al.  Reorganization of retinotopic cortical maps in adult mammals after lesions of the retina. , 1990, Science.

[78]  J. Kaas,et al.  The reorganization of somatosensory cortex following peripheral nerve damage in adult and developing mammals. , 1983, Annual review of neuroscience.

[79]  Eric I Knudsen,et al.  Hunting Increases Adaptive Auditory Map Plasticity in Adult Barn Owls , 2005, The Journal of Neuroscience.

[80]  Bruno Bontempi,et al.  The Formation of Recent and Remote Memory Is Associated with Time-Dependent Formation of Dendritic Spines in the Hippocampus and Anterior Cingulate Cortex , 2009, The Journal of Neuroscience.

[81]  C. Stosiek,et al.  In vivo two-photon calcium imaging of neuronal networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[82]  B. Sakmann,et al.  Whisker movements evoked by stimulation of single pyramidal cells in rat motor cortex , 2004, Nature.

[83]  A. Borst,et al.  A genetically encoded calcium indicator for chronic in vivo two-photon imaging , 2008, Nature Methods.

[84]  Y. Miyashita Neuronal correlate of visual associative long-term memory in the primate temporal cortex , 1988, Nature.

[85]  K. Svoboda,et al.  Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window , 2009, Nature Protocols.

[86]  Alcino J. Silva,et al.  Calmodulin-Kinases: Modulators of Neuronal Development and Plasticity , 2009, Neuron.

[87]  M P Stryker,et al.  Rapid remodeling of axonal arbors in the visual cortex. , 1993, Science.

[88]  Sreekanth H. Chalasani,et al.  Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators , 2009, Nature Methods.

[89]  T. Tsumoto,et al.  Difference in Binocularity and Ocular Dominance Plasticity between GABAergic and Excitatory Cortical Neurons , 2010, The Journal of Neuroscience.

[90]  C. Gilbert,et al.  Rapid Axonal Sprouting and Pruning Accompany Functional Reorganization in Primary Visual Cortex , 2009, Neuron.

[91]  Y. Miyashita,et al.  Neural organization for the long-term memory of paired associates , 1991, Nature.

[92]  M. Stryker,et al.  Ocular dominance in layer IV of the cat's visual cortex and the effects of monocular deprivation. , 1978, The Journal of physiology.

[93]  Y. Frégnac,et al.  A cellular analogue of visual cortical plasticity , 1988, Nature.

[94]  T. Oertner,et al.  Functional Imaging of Single Synapses in Brain Slices , 2002, Experimental physiology.

[95]  D. Tank,et al.  A Miniature Head-Mounted Two-Photon Microscope High-Resolution Brain Imaging in Freely Moving Animals , 2001, Neuron.

[96]  R. Yuste,et al.  Non-synaptic dendritic spines in neocortex , 2007, Neuroscience.

[97]  C. Gilbert,et al.  Axons and Synaptic Boutons Are Highly Dynamic in Adult Visual Cortex , 2006, Neuron.

[98]  T. Bliss,et al.  Ultrastructural synaptic correlates of spatial learning in rat hippocampus , 1997, Neuroscience.

[99]  Y. Dudai Neurogenetic dissection of learning and short-term memory in Drosophila. , 1988, Annual review of neuroscience.