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PLOS ONE  2013 

Fear Learning Increases the Number of Polyribosomes Associated with Excitatory and Inhibitory Synapses in the Barrel Cortex

DOI: 10.1371/journal.pone.0054301

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Abstract:

Associative fear learning, resulting from whisker stimulation paired with application of a mild electric shock to the tail in a classical conditioning paradigm, changes the motor behavior of mice and modifies the cortical functional representation of sensory receptors involved in the conditioning. It also induces the formation of new inhibitory synapses on double-synapse spines of the cognate barrel hollows. We studied density and distribution of polyribosomes, the putative structural markers of enhanced synaptic activation, following conditioning. By analyzing serial sections of the barrel cortex by electron microscopy and stereology, we found that the density of polyribosomes was significantly increased in dendrites of the barrel activated during conditioning. The results revealed fear learning-induced increase in the density of polyribosomes associated with both excitatory and inhibitory synapses located on dendritic spines (in both single- and double-synapse spines) and only with the inhibitory synapses located on dendritic shafts. This effect was accompanied by a significant increase in the postsynaptic density area of the excitatory synapses on single-synapse spines and of the inhibitory synapses on double-synapse spines containing polyribosomes. The present results show that associative fear learning not only induces inhibitory synaptogenesis, as demonstrated in the previous studies, but also stimulates local protein synthesis and produces modifications of the synapses that indicate their potentiation.

References

[1]  Bailey CH, Chen M (1988) Long-term sensitization in Aplysia increases the number of presynaptic contacts onto the identified gill motor neuron L7. Proc Natl Acad Sci USA 85: 9356–9359.
[2]  Black JE, Isaacs KR, Anderson BJ, Alcantara AA, Greenough WT (1990) Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proc Natl Acad Sci USA 87: 5568–5572.
[3]  Kleim JA, Lussnig E, Schwarz ER, Comery TA, Greenough WT (1996) Synaptogenesis and Fos expression in the motor cortex of the adult rat after motor skill learning. J Neurosci 16: 4529–4535.
[4]  Hunter A, Stewart MG (1993) Long-term increases in the numerical density of synapses in the chick lobus parolfactorius after passive avoidance training. Brain Res 605: 251–255.
[5]  Knafo S, Ariav G, Barkai E, Libersat F (2004) Olfactory learning-induced increase in spine density along the apical dendrites of CA1 hippocampal neurons. Hippocampus 14: 819–825.
[6]  Xu T, Yu X, Perlik AJ, Tobin WF, Zweig JA, et al. (2009) Rapid formation and selective stabilization of synapses for enduring motor memories. Nature 462: 915–919.
[7]  Jones MS, Barth DS (1997) Sensory-evoked high-frequency (gamma-band) oscillating potentials in somatosensory cortex of the unanesthetized rat. Brain Res 768: 167–176.
[8]  Knott GW, Quairiaux C, Genoud C, Welker E (2002) Formation of dendritic spines with GABAergic synapses induced by whisker stimulation in adult mice. Neuron 34: 265–273.
[9]  Majewska AK, Newton JR, Sur M (2006) Remodeling of synaptic structure in sensory cortical areas in vivo. J Neurosci. 26: 3021–3029.
[10]  Holtmaat A, De Paola V, Wilbrecht L, Knott GW (2008) Imaging of experience-dependent structural plasticity in the mouse neocortex in vivo. Behav Brain Res 192: 20–25.
[11]  Yu H, Majewska AK, Sur M (2011) Rapid experience-dependent plasticity of synapse function and structure in ferret visual cortex in vivo. Proc Natl Acad Sci USA 108: 21235–21240.
[12]  Ostroff LE, Cain CK, Bedont J, Monfils MH, Ledoux JE (2010) Fear and safety learning differentially affect synapse size and dendritic translation in the lateral amygdala. Proc Natl Acad Sci USA 107: 9418–9423.
[13]  Lushnikova I, Skibo G, Muller D, Nikonenko I (2011) Excitatory synaptic activity is associated with a rapid structural plasticity of inhibitory synapses on hippocampal CA1 pyramidal cells. Neuropharmacology 60: 757–764.
[14]  Bourne JN, Harris KM (2011) Coordination of size and number of excitatory and inhibitory synapses results in a balanced structural plasticity along mature hippocampal CA1 dendrites during LTP. Hippocampus 21: 354–373.
[15]  Woosley TA, Van Der Loos (1970) H (1970) The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex: The description of a cortical field composed of discrete cytoarchitectonic units. Brain Res 17: 205–242.
[16]  Siucinska E, Kossut M (1996) Short-lasting classical conditioning induces reversible changes of representational maps of whiskers in mouse SI cortex – a 2DG study. Cereb Cortex 6: 506–513.
[17]  Cybulska-Klosowicz A, Zakrzewska R, Kossut M (2009) Brain activation patterns during classical conditioning with appetitive or aversive UCS. Behav Brain Res 204: 102–111.
[18]  Siucinska E, Kossut M, Stewart MG (1999) GABA immunoreactivity in mouse barrel field after aversive and appetitive classical conditioning training involving facial vibrissae. Brain Res 843: 62–70.
[19]  Gierdalski M, Jablonska B, Siucinska E, Lech M, Skibinska A, et al. (2001) Rapid regulation of GAD67 mRNA and protein level in cortical neurons after sensory learning. Cereb Cortex 11: 806–815.
[20]  Jasinska M, Siucinska E, Cybulska-Klosowicz A, Pyza E, Furness DN, et al. (2010) Rapid, learning-induced inhibitory synaptogenesis in murine barrel field. J Neurosci 30: 1176–1184.
[21]  Tokarski K, Urban-Ciecko J, Kossut M, Hess G (2007) Sensory learning-induced enhancement of inhibitory synaptic transmission in the barrel cortex of the mouse. Eur J Neurosci 26: 134–141.
[22]  Skibinska A, Lech M, Kossut M (2005) Differential regulation of cortical NMDA receptor subunits by sensory learning. Brain Res 1065: 26–36.
[23]  Ostroff LE, Fiala JC, Allwardt B, Harris KM (2002) Polyribosomes redistribute from dendritic shafts into spines with enlarged synapses during LTP in developing rat hippocampal slices. Neuron 35: 535–545.
[24]  Bourne JN, Sorra KE, Hurlburt J, Harris KM (2007) Polyribosomes are increased in spines of CA1 dendrites 2 h after the induction of LTP in mature rat hippocampal slices. Hippocampus 17: 1–4.
[25]  Steward O, Schuman EM (2001) Protein synthesis at synaptic sites on dendrites. Annu Rev Neurosci 24: 299–325.
[26]  Witcher MR, Park YD, Lee MR, Sharma S, Harris KM, et al. (2010) Three-dimensional relationships between perisynaptic astroglia and human hippocampal synapses. Glia 58: 572–587.
[27]  Steward O, Ribak CE (1986) Polyribosomes associated with synaptic specializations on axon initial segments: localization of protein-synthetic machinery at inhibitory synapses. J Neurosci 6: 3079–3085.
[28]  Fiala JC, Harris KM (2001) Extending unbiased stereology of brain ultrastructure to three-dimensional volumes. J Am Med Inform Assoc 8: 1–16.
[29]  Jasińska M, Siucińska E, G?azewski S, Pyza E, Kossut M (2006) Characterization and plasticity of the double synapse spines in the barrel cortex of the mouse. Acta Neurobiol Exp (Wars) 66: 99–104.
[30]  Dictenberg JB, Swanger SA, Antar LN, Singer RH, Bassell GJ (2008) A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome. Dev Cell 14: 926–939.
[31]  Racca C, Gardiol A, Eom T, Ule J, Triller A, et al. (2010) The Neuronal Splicing Factor Nova Co-Localizes with Target RNAs in the Dendrite. Front Neural Circuits 4: 5.
[32]  Takumi Y, Ramírez-León V, Laake P, Rinvik E, Ottersen OP (1999) Different modes of expression of AMPA and NMDA receptors in hippocampal synapses. Nat Neurosci 2: 618–624.
[33]  Ganeshina O, Berry RW, Petralia RS, Nicholson DA, Geinisman Y (2004) Synapses with a segmented, completely partitioned postsynaptic density express more AMPA receptors than other axospinous synaptic junctions. Neuroscience 125: 615–623.
[34]  Ganeshina O, Berry RW, Petralia RS, Nicholson DA, Geinisman Y (2004) Differences in the expression of AMPA and NMDA receptors between axospinous perforated and nonperforated synapses are related to the configuration and size of postsynaptic densities. J Comp Neurol 468: 86–95.
[35]  Steward O, Levy WB (1982) Preferential localization of polyribosomes under the base of dendritic spines in granule cells of the dentate gyrus. J Neurosci 2: 284–291.
[36]  Steward O, Schuman EM (2003) Compartmentalized synthesis and degradation of proteins in neurons. Neuron 40: 347–359.
[37]  Cajigas IJ, Tushev G, Will TJ, Dieck S, Fuerst N, et al. (2012) The local transcriptome in the synaptic neuropil revealed by deep sequencing and high-resolution imaging. Neuron 74: 453–66.
[38]  Martin KC, Zukin RS (2006) RNA trafficking and local protein synthesis in dendrites: an overview. J Neurosci 26: 7131–7134.
[39]  Scheetz AJ, Nairn AC, Constantine-Paton M (2000) NMDA receptor-mediated control of protein synthesis at developing synapses. Nat Neurosci 3: 211–216.
[40]  Wells DG, Richter JD, Fallon JR (2000) Molecular mechanisms for activity-regulated protein synthesis in the synapto-dendritic compartment. Curr Opin Neurobiol 10: 132–137.
[41]  Todd PK, Mack KJ, Malter JS (2003) The fragile X mental retardation protein is required for type-I metabotropic glutamate receptor-dependent translation of PSD-95. Proc Natl Acad Sci U S A 100: 14374–14378.
[42]  Lee CC, Huang CC, Wu MY, Hsu KS (2005) Insulin stimulates postsynaptic density-95 protein translation via the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway. J Biol Chem 280: 18543–18550.
[43]  Skibinska A, Lech M, Kossut M (2001) PSD95 protein level rises in murine somatosensory cortex after sensory training. Neuroreport 12: 2907–2910.
[44]  Gray NW, Weimer RM, Bureau I, Svoboda K (2006) Rapid redistribution of synaptic PSD-95 in the neocortex in vivo. PLoS Biol 4: e370.
[45]  Li Z, Sheng M (2003) Some assembly required: the development of neuronal synapses. Nat Rev Mol Cell Biol 4: 833–41.
[46]  Froemke RC, Merzenich MM, Schreiner CE (2007) A synaptic memory trace for cortical receptive field plasticity. Nature 450: 425–429.
[47]  Galindo-Leon EE, Lin FG, Liu RC (2009) Inhibitory plasticity in a lateral band improves cortical detection of natural vocalizations. Neuron 62: 705–716.
[48]  Brosh I, Barkai E (2009) Learning-induced enhancement of feedback inhibitory synaptic transmission. Learn Mem 16: 413–416.
[49]  Saar D, Reuveni I, Barkai E (2011) Mechanisms underlying rule learning-induced enhancement of excitatory and inhibitory transmission. J Neurophysiol 107: 1222–1229.
[50]  Bekisz M, Garkun Y, Wabno J, Hess G, Wrobel A, et al. (2001) Increased excitability of cortical neurons induced by associative learning: an ex vivo study. Eur J Neurosci 32: 1715–1725.
[51]  Sun QQ, Hugenard JR, Proince DA (2006) Barrel cortex microcircuits: thalamic inhibition in spiny stellate cells is mediated by a small number of fast-spiking neurons. J Neurosci 26: 1219–1230.
[52]  Miller KD, Pinto DJ, Simons DJ (2001) Processing in layer 4 of the neocortical circuit: New insights from visual and somatosensory cortex. Curr Opin Neurobiol 11: 488–497.

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