The role of dendritic inhibition in shaping the plasticity of excitatory synapses

Using computational tools we explored the impact of local synaptic inhibition on the plasticity of excitatory synapses in dendrites. The latter critically depends on the intracellular concentration of calcium, which in turn, depends on membrane potential and thus on inhibitory activity in particular dendritic compartments. We systematically characterized the dependence of excitatory synaptic plasticity on dendritic morphology, loci and strength, as well as on the spatial distribution of inhibitory synapses and on the level of excitatory activity. Plasticity of excitatory synapses may attain three states: “protected” (unchanged), potentiated (long-term potentiation; LTP), or depressed (long-term depression; LTD). The transition between these three plasticity states could be finely tuned by synaptic inhibition with high spatial resolution. Strategic placement of inhibition could give rise to the co-existence of all three states over short dendritic branches. We compared the plasticity effect of the innervation patterns typical of different inhibitory subclasses—Chandelier, Basket, Martinotti, and Double Bouquet—in a detailed model of a layer 5 pyramidal cell. Our study suggests that dendritic inhibition plays a key role in shaping and fine-tuning excitatory synaptic plasticity in dendrites.

[1]  H. Markram,et al.  Disynaptic Inhibition between Neocortical Pyramidal Cells Mediated by Martinotti Cells , 2007, Neuron.

[2]  G. Buzsáki,et al.  Pattern and inhibition-dependent invasion of pyramidal cell dendrites by fast spikes in the hippocampus in vivo. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[3]  B. Sakmann,et al.  Neuronal correlates of local, lateral, and translaminar inhibition with reference to cortical columns. , 2009, Cerebral cortex.

[4]  G. Lynch,et al.  Intracellular injections of EGTA block induction of hippocampal long-term potentiation , 1983, Nature.

[5]  Nicholas T. Carnevale,et al.  The NEURON Simulation Environment , 1997, Neural Computation.

[6]  R. Lashgari,et al.  Effects of GABAergic inhibition on neocortical long-term potentiation in the chronically prepared rat , 2007, Neuroscience Letters.

[7]  J. Lisman,et al.  A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Rafael Yuste,et al.  From form to function: calcium compartmentalization in dendritic spines , 2000, Nature Neuroscience.

[9]  W. Singer,et al.  Relation Between Dendritic Ca2+ Levels and the Polarity of Synaptic Long‐term Modifications in Rat Visual Cortex Neurons , 1997, The European journal of neuroscience.

[10]  C. Gilbert,et al.  Axonal Dynamics of Excitatory and Inhibitory Neurons in Somatosensory Cortex , 2010, PLoS biology.

[11]  T. Bonhoeffer,et al.  GABAergic synapses are formed without the involvement of dendritic protrusions , 2008, Nature Neuroscience.

[12]  O. Paulsen,et al.  Maturation of Long-Term Potentiation Induction Rules in Rodent Hippocampus: Role of GABAergic Inhibition , 2003, The Journal of Neuroscience.

[13]  Dmitri B. Chklovskii,et al.  Wiring Optimization in Cortical Circuits , 2002, Neuron.

[14]  A. C. Greenwood,et al.  Bidirectional synaptic plasticity correlated with the magnitude of dendritic calcium transients above a threshold. , 2001, Journal of neurophysiology.

[15]  W. Singer,et al.  Different voltage-dependent thresholds for inducing long-term depression and long-term potentiation in slices of rat visual cortex , 1990, Nature.

[16]  J Rinzel,et al.  Branch input resistance and steady attenuation for input to one branch of a dendritic neuron model. , 1973, Biophysical journal.

[17]  P. Somogyi,et al.  Neuronal Diversity and Temporal Dynamics: The Unity of Hippocampal Circuit Operations , 2008, Science.

[18]  Dejan Zecevic,et al.  Cortical dendritic spine heads are not electrically isolated by the spine neck from membrane potential signals in parent dendrites. , 2014, Cerebral cortex.

[19]  Andreas T. Schaefer,et al.  Coincidence detection in pyramidal neurons is tuned by their dendritic branching pattern. , 2003, Journal of neurophysiology.

[20]  Guosong Liu,et al.  Local structural balance and functional interaction of excitatory and inhibitory synapses in hippocampal dendrites , 2004, Nature Neuroscience.

[21]  J. D. McGaugh,et al.  Interaction of beta-endorphin and GABAergic drugs in the regulation of memory storage. , 1993, Behavioral and neural biology.

[22]  T. Freund,et al.  Differences between Somatic and Dendritic Inhibition in the Hippocampus , 1996, Neuron.

[23]  D. Debanne,et al.  Long‐term synaptic plasticity between pairs of individual CA3 pyramidal cells in rat hippocampal slice cultures , 1998, The Journal of physiology.

[24]  H. Markram,et al.  Interneurons of the neocortical inhibitory system , 2004, Nature Reviews Neuroscience.

[25]  N. Spruston.  Pyramidal neurons: dendritic structure and synaptic integration , 2008, Nature Reviews Neuroscience.

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

[27]  D. Clapham,et al.  NMDA receptors amplify calcium influx into dendritic spines during associative pre- and postsynaptic activation , 1998, Nature Neuroscience.

[28]  Rodney J. Douglas,et al.  Inhibition in cortical circuits , 2009, Current Biology.

[29]  H. Markram,et al.  Anatomical, physiological and molecular properties of Martinotti cells in the somatosensory cortex of the juvenile rat , 2004, The Journal of physiology.

[30]  J Rinzel,et al.  Transient response in a dendritic neuron model for current injected at one branch. , 1974, Biophysical journal.

[31]  D. Schmechel,et al.  Variability in the terminations of GABAergic chandelier cell axons on initial segments of pyramidal cell axons in the monkey sensory‐motor cortex , 1985, The Journal of comparative neurology.

[32]  D. Johnston,et al.  A Synaptically Controlled, Associative Signal for Hebbian Plasticity in Hippocampal Neurons , 1997, Science.

[33]  R. Zucker,et al.  Selective induction of LTP and LTD by postsynaptic [Ca2+]i elevation. , 1999, Journal of neurophysiology.

[34]  Elly Nedivi,et al.  Clustered Dynamics of Inhibitory Synapses and Dendritic Spines in the Adult Neocortex , 2012, Neuron.

[35]  P. Somogyi,et al.  Synaptic connections of morphologically identified and physiologically characterized large basket cells in the striate cortex of cat , 1983, Neuroscience.

[36]  B. Sakmann,et al.  A new cellular mechanism for coupling inputs arriving at different cortical layers , 1999, Nature.

[37]  Yi Zuo,et al.  Spine Neck Plasticity Controls Postsynaptic Calcium Signals through Electrical Compartmentalization , 2008, The Journal of Neuroscience.

[38]  A. Peters,et al.  The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines. , 1970, The American journal of anatomy.

[39]  Jun Noguchi,et al.  Spatial Distributions of GABA Receptors and Local Inhibition of Ca2+ Transients Studied with GABA Uncaging in the Dendrites of CA1 Pyramidal Neurons , 2011, PloS one.

[40]  R Y Tsien,et al.  Calcium channels, stores, and oscillations. , 1990, Annual review of cell biology.

[41]  Tobias Bonhoeffer,et al.  Loss of Sensory Input Causes Rapid Structural Changes of Inhibitory Neurons in Adult Mouse Visual Cortex , 2011, Neuron.

[42]  H. Wigström,et al.  Facilitation of hippocampal long-lasting potentiation by GABA antagonists. , 1985, Acta physiologica Scandinavica.

[43]  P. J. Sjöström,et al.  Rate, Timing, and Cooperativity Jointly Determine Cortical Synaptic Plasticity , 2001, Neuron.

[44]  W. Singer,et al.  Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation , 1993, Trends in Neurosciences.

[45]  R. Yuste,et al.  On the function of dendritic spines. , 2001, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[46]  J. Lisman,et al.  A Model of Synaptic Memory A CaMKII/PP1 Switch that Potentiates Transmission by Organizing an AMPA Receptor Anchoring Assembly , 2001, Neuron.

[47]  R. Malenka,et al.  Temporal limits on the rise in postsynaptic calcium required for the induction of long-term potentiation , 1992, Neuron.

[48]  G. Bi,et al.  Synaptic Modifications in Cultured Hippocampal Neurons: Dependence on Spike Timing, Synaptic Strength, and Postsynaptic Cell Type , 1998, The Journal of Neuroscience.

[49]  W. Gerstner,et al.  Connectivity reflects coding: a model of voltage-based STDP with homeostasis , 2010, Nature Neuroscience.

[50]  A. Polsky,et al.  Synaptic Integration in Tuft Dendrites of Layer 5 Pyramidal Neurons: A New Unifying Principle , 2009, Science.

[51]  G. Elston,et al.  Distribution and patterns of connectivity of interneurons containing calbindin, calretinin, and parvalbumin in visual areas of the occipital and temporal lobes of the macaque monkey , 1999, The Journal of comparative neurology.

[52]  A. Cowey,et al.  The axo-axonic interneuron in the cerebral cortex of the rat, cat and monkey , 1982, Neuroscience.

[53]  M. Cynader,et al.  Quantitative distribution of GABA-immunopositive and -immunonegative neurons and synapses in the monkey striate cortex (area 17). , 1992, Cerebral cortex.

[54]  Idan Segev,et al.  Principles Governing the Operation of Synaptic Inhibition in Dendrites , 2012, Neuron.

[55]  Michael L. Hines,et al.  The NEURON Book , 2006 .

[56]  M. Berridge,et al.  The versatility and universality of calcium signalling , 2000, Nature Reviews Molecular Cell Biology.

[57]  A. Cowey,et al.  Combined golgi and electron microscopic study on the synapses formed by double bouquet cells in the visual cortex of the cat and monkey , 1981, The Journal of comparative neurology.

[58]  C. Koch,et al.  The function of dendritic spines: devices subserving biochemical rather than electrical compartmentalization , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[59]  Grzegorz Hess.  Synaptic plasticity of local connections in rat motor cortex. , 2004, Acta neurobiologiae experimentalis.

[60]  H. Wigström,et al.  Long‐term potentiation involves enhanced synaptic excitation relative to synaptic inhibition in guinea‐pig hippocampus. , 1987, The Journal of physiology.

[61]  Chris I. De Zeeuw,et al.  Elimination of Inhibitory Synapses Is a Major Component of Adult Ocular Dominance Plasticity , 2012, Neuron.

[62]  S. Nelson,et al.  Potentiation of cortical inhibition by visual deprivation , 2006, Nature.

[63]  B. Sakmann,et al.  Calcium dynamics in single spines during coincident pre- and postsynaptic activity depend on relative timing of back-propagating action potentials and subthreshold excitatory postsynaptic potentials. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[64]  R. Racine,et al.  GABAergic modulation of neocortical long‐term potentiation in the freely moving rat , 2000, Synapse.

[65]  B. Gustafsson,et al.  Long‐term Potentiation and Field EPSPs in the Lateral and Medial Perforant Paths in the Dentate Gyrus In Vitro: a Comparison , 1992, The European journal of neuroscience.

[66]  W. N. Ross,et al.  IPSPs modulate spike backpropagation and associated [Ca2+]i changes in the dendrites of hippocampal CA1 pyramidal neurons. , 1996, Journal of neurophysiology.

[67]  E. G. Jones,et al.  Synapses of double bouquet cells in monkey cerebral cortex visualized by calbindin immunoreactivity , 1989, Brain Research.

[68]  Bartlett W. Mel,et al.  Location-Dependent Effects of Inhibition on Local Spiking in Pyramidal Neuron Dendrites , 2012, PLoS Comput. Biol..

[69]  Huibert D. Mansvelder,et al.  Distributed Network Actions by Nicotine Increase the Threshold for Spike-Timing-Dependent Plasticity in Prefrontal Cortex , 2007, Neuron.

[70]  H. Markram,et al.  Regulation of Synaptic Efficacy by Coincidence of Postsynaptic APs and EPSPs , 1997, Science.

[71]  G M Shepherd,et al.  The dendritic spine: a multifunctional integrative unit. , 1996, Journal of neurophysiology.

[72]  W. Rall.  Branching dendritic trees and motoneuron membrane resistivity. , 1959, Experimental neurology.

[73]  D. Feldman,et al.  Timing-Based LTP and LTD at Vertical Inputs to Layer II/III Pyramidal Cells in Rat Barrel Cortex , 2000, Neuron.

[74]  Rafael Yuste,et al.  Book Review: On the Function of Dendritic Spines , 2001 .

[75]  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.

[76]  Takeshi Aihara,et al.  Spatial analysis of spike‐timing‐dependent LTP and LTD in the CA1 area of hippocampal slices using optical imaging , 2005, Hippocampus.

[77]  W. Denk,et al.  Dendritic spines as basic functional units of neuronal integration , 1995, Nature.

[78]  L. Cooper,et al.  A unified model of NMDA receptor-dependent bidirectional synaptic plasticity , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[79]  C. Chapman,et al.  Effects of GABAA inhibition on the expression of long‐term potentiation in CA1 pyramidal cells are dependent on tetanization parameters , 1998, Hippocampus.

[80]  Siu Kang,et al.  Bidirectional plasticity in fast-spiking GABA circuits by visual experience , 2009, Nature.

[81]  U. Eysel,et al.  Metabotropic glutamate receptors mediate expression of LTP in slices of rat visual cortex , 2002, The European journal of neuroscience.

[82]  W Rall,et al.  Computational study of an excitable dendritic spine. , 1988, Journal of neurophysiology.

[83]  D. Tropea,et al.  Synaptic plasticity of feedback connections in rat visual cortex. , 1999, Brain research. Developmental brain research.

[84]  Robert S. Zucker,et al.  Postsynaptic Levels of [Ca2+]i Needed to Trigger LTD and LTP , 1996, Neuron.

[85]  N. Hu,et al.  Diazepam inhibits the induction and maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn of rats , 2006, Neuropharmacology.

[86]  M. W. Brown,et al.  An experimental test of the role of postsynaptic calcium levels in determining synaptic strength using perirhinal cortex of rat , 2001, The Journal of physiology.

[87]  L. Cooper,et al.  Synaptic homeostasis and input selectivity follow from a calcium-dependent plasticity model. , 2004, Proceedings of the National Academy of Sciences of the United States of America.