Homeostatic shutdown of long-term potentiation in the adult hippocampus.

Homeostasis is a key concept in biology. It enables ecosystems, organisms, organs, and cells to adjust their operating range to values that ensure optimal performance. Homeostatic regulation of the strength of neuronal connections has been shown to play an important role in the development of the nervous system. Here we investigate whether mature neurons also possess mechanisms to prevent the strengthening of input synapses once the limit of their operating range has been reached. Using electrophysiological recordings in hippocampal slices, we show that such a mechanism exists but comes into play only after a considerable number of synapses have been potentiated. Thus, adult neurons can sustain a substantial amount of synaptic strengthening but, once a certain threshold of potentiation is exceeded, homeostatic regulation ensures that no further strengthening can occur.

[1]  D. Debanne,et al.  Long-term plasticity of intrinsic excitability: learning rules and mechanisms. , 2003, Learning & memory.

[2]  L. Frank,et al.  Single Neurons in the Monkey Hippocampus and Learning of New Associations , 2003, Science.

[3]  G. Shepherd,et al.  Three-Dimensional Structure and Composition of CA3→CA1 Axons in Rat Hippocampal Slices: Implications for Presynaptic Connectivity and Compartmentalization , 1998, The Journal of Neuroscience.

[4]  M. Mauk,et al.  Distinct LTP induction mechanisms: contribution of NMDA receptors and voltage-dependent calcium channels. , 1995, Journal of neurophysiology.

[5]  Marco Fuenzalida,et al.  Heterosynaptic metaplastic regulation of synaptic efficacy in CA1 pyramidal neurons of rat hippocampus , 2004, Hippocampus.

[6]  Henry Schmitz,et al.  Congenital Hemolytic Anemias , 1942 .

[7]  Bruce L. McNaughton,et al.  Making room for new memories , 2002, Nature Neuroscience.

[8]  R. French Catastrophic forgetting in connectionist networks , 1999, Trends in Cognitive Sciences.

[9]  James L. McClelland,et al.  Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. , 1995, Psychological review.

[10]  M. Moser,et al.  Is learning blocked by saturation of synaptic weights in the hippocampus? , 1999, Neuroscience and Biobehavioral Reviews.

[11]  R. Morris,et al.  Competing for Memory Hippocampal LTP under Regimes of Reduced Protein Synthesis , 2004, Neuron.

[12]  D. Diamond,et al.  Stress generates emotional memories and retrograde amnesia by inducing an endogenous form of hippocampal LTP , 2004, Hippocampus.

[13]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[14]  D. Debanne,et al.  Heterogeneity of Synaptic Plasticity at Unitary CA3–CA1 and CA3–CA3 Connections in Rat Hippocampal Slice Cultures , 1999, The Journal of Neuroscience.

[15]  B. Gustafsson,et al.  TEA elicits two distinct potentiations of synaptic transmission in the CA1 region of the hippocampal slice , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[16]  H. Eichenbaum,et al.  Spatial and behavioral correlates of hippocampal neuronal activity , 1989 .

[17]  R Ratcliff,et al.  Connectionist models of recognition memory: constraints imposed by learning and forgetting functions. , 1990, Psychological review.

[18]  H. Kuo,et al.  Upregulation of IL-5 receptor expression on bone marrow-derived CD34+ cells from patients with asthma. , 1999, Changgeng yi xue za zhi.

[19]  L. Squire Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. , 1992, Psychological review.

[20]  D. Rusakov,et al.  Repeated confocal imaging of individual dendritic spines in the living hippocampal slice: evidence for changes in length and orientation associated with chemically induced LTP , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  G. Davis,et al.  Maintaining the stability of neural function: a homeostatic hypothesis. , 2001, Annual review of physiology.

[22]  R. Morris,et al.  Impaired spatial learning after saturation of long-term potentiation. , 1998, Science.

[23]  Morten Raastad,et al.  The hippocampal lamella hypothesis revisited 1 1 Published on the World Wide Web on 12 October 2000. , 2000, Brain Research.

[24]  S. Royer,et al.  Conservation of total synaptic weight through balanced synaptic depression and potentiation , 2003, Nature.

[25]  W. Abraham,et al.  Metaplasticity: A new vista across the field of synaptic plasticity , 1997, Progress in Neurobiology.

[26]  M. Bear,et al.  Experience-dependent modification of synaptic plasticity in visual cortex , 1996, Nature.

[27]  T. Freund,et al.  Total number and distribution of inhibitory and excitatory synapses on hippocampal CA1 pyramidal cells , 2001, Neuroscience.

[28]  M. Bear,et al.  Metaplasticity: the plasticity of synaptic plasticity , 1996, Trends in Neurosciences.

[29]  J. Donoghue,et al.  Learning-induced LTP in neocortex. , 2000, Science.

[30]  Massimo Scanziani,et al.  Role of intercellular interactions in heterosynaptic long-term depression , 1996, Nature.

[31]  G. Lynch,et al.  Heterosynaptic depression: a postsynaptic correlate of long-term potentiation , 1977, Nature.

[32]  Y. Ben-Ari,et al.  Novel form of long-term potentiation produced by a K+channel blocker in the hippocampus , 1991, Nature.

[33]  Niraj S. Desai,et al.  Activity-dependent scaling of quantal amplitude in neocortical neurons , 1998, Nature.

[34]  R. Chitwood,et al.  Activity-dependent decrease of excitability in rat hippocampal neurons through increases in Ih , 2005, Nature Neuroscience.

[35]  W. Wadman,et al.  Homeostatic scaling of neuronal excitability by synaptic modulation of somatic hyperpolarization-activated Ih channels. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Joseph E LeDoux,et al.  Postsynaptic Receptor Trafficking Underlying a Form of Associative Learning , 2005, Science.

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

[38]  L. Cooper,et al.  A physiological basis for a theory of synapse modification. , 1987, Science.

[39]  R. Malenka,et al.  The influence of prior synaptic activity on the induction of long-term potentiation. , 1992, Science.

[40]  Yy Huang,et al.  Examination of TEA-induced synaptic enhancement in area CA1 of the hippocampus: the role of voltage-dependent Ca2+ channels in the induction of LTP , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[41]  Philip Goelet,et al.  The long and the short of long–term memory—a molecular framework , 1986, Nature.

[42]  H Wang,et al.  Priming-induced shift in synaptic plasticity in the rat hippocampus. , 1999, Journal of neurophysiology.

[43]  T. Bliss,et al.  Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path , 1973, The Journal of physiology.

[44]  H. Eichenbaum,et al.  The global record of memory in hippocampal neuronal activity , 1999, Nature.

[45]  C. A. Castro,et al.  Recovery of spatial learning deficits after decay of electrically induced synaptic enhancement in the hippocampus , 1989, Nature.

[46]  F. Attneave,et al.  The Organization of Behavior: A Neuropsychological Theory , 1949 .