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Functional consequences of age-related morphologic changes to pyramidal neurons of the rhesus monkey prefrontal cortex

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Abstract

Layer 3 (L3) pyramidal neurons in the lateral prefrontal cortex (LPFC) of rhesus monkeys exhibit dendritic regression, spine loss and increased action potential (AP) firing rates during normal aging. The relationship between these structural and functional alterations, if any, is unknown. To address this issue, morphological and electrophysiological properties of L3 LPFC pyramidal neurons from young and aged rhesus monkeys were characterized using in vitro whole-cell patch-clamp recordings and high-resolution digital reconstruction of neurons. Consistent with our previous studies, aged neurons exhibited significantly reduced dendritic arbor length and spine density, as well as increased input resistance and firing rates. Computational models using the digital reconstructions with Hodgkin-Huxley and AMPA channels allowed us to assess relationships between demonstrated age-related changes and to predict physiological changes that have not yet been tested empirically. For example, the models predict that in both backpropagating APs and excitatory postsynaptic currents (EPSCs), attenuation is lower in aged versus young neurons. Importantly, when identical densities of passive parameters and voltage- and calcium-gated conductances were used in young and aged model neurons, neither input resistance nor firing rates differed between the two age groups. Tuning passive parameters for each model predicted significantly higher membrane resistance (R m ) in aged versus young neurons. This R m increase alone did not account for increased firing rates in aged models, but coupling these R m values with subtle differences in morphology and membrane capacitance did. The predicted differences in passive parameters (or parameters with similar effects) are mathematically plausible, but must be tested empirically.

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References

  • Amatrudo, J., Weaver, C. M., Crimins, J. L., Hof, P. R., Rosene, D. L., & Luebke, J. I. (2012). Influence of highly distinctive structural properties on the excitability of pyramidal neurons in monkey visual and prefrontal cortices. Journal of Neuroscience, 32(40), 13644–13660.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Antic, S. D., Zhou, W. L., Moore, A. R., Short, S. M., & Ikonomu, K. D. (2010). The decade of the dendritic NMDA spike. Journal of Neuroscience Research, 88(14), 2991–3001.

    Article  CAS  PubMed  Google Scholar 

  • Bai, L., Hof, P. R., Standaert, D. G., Xing, Y., Nelson, S. E., Young, A. B., & Magnusson, K. R. (2004). Changes in the expression of the NR2B subunit during aging in macaque monkeys. Neurobiology of Aging, 25(2), 201–208.

    Article  CAS  PubMed  Google Scholar 

  • Blalock, E. M., Porter, N. M., & Landfield, P. W. (1999). Decreased G-protein-mediated regulation and shift in calcium channel types with age in hippocampal cultures. Journal of Neuroscience, 19(19), 8674–8684.

    CAS  PubMed  Google Scholar 

  • Branco, T., & Hausser, M. (2010). The single dendritic branch as a fundamental functional unit in the nervous system. Current Opinion in Neurobiology, 20(4), 494–502.

    Article  CAS  PubMed  Google Scholar 

  • Brown, T. H., Zador, A., Mainen, Z. F., & Claiborne, B. J. (1992). Hebbian computations in hippocampal dendrites and spines. In T. McKenna, J. Davis, & S. F. Zornetzer (Eds.), Single Neuron Computation (pp. 81–116). San Diego: Academic.

    Chapter  Google Scholar 

  • Cannon, R. C., Turner, D. A., Pyapali, G. K., & Wheal, H. V. (1998). An on-line archive of reconstructed hippocampal neurons. Journal of Neuroscience Methods, 84, 49–54.

    Article  CAS  PubMed  Google Scholar 

  • Carnevale, N. T. (2010). IClamp experiment with custom initialization. http://www.neuron.yale.edu/ftp/ted/neuron/iclamp_experiment_with_custom_init.zip. Accessed 30 Sep 2012.

  • Carnevale, N. T., & Hines, M. L. (2006). The NEURON book. Cambridge: Cambridge University Press.

    Book  Google Scholar 

  • Carnevale, N. T., Tsai, K. Y., Claiborne, B. J., & Brown, T. H. (1997). Comparative electrotonic analysis of three classes of rat hippocampal neurons. Journal of Neurophysiology, 78(2), 703–720.

    CAS  PubMed  Google Scholar 

  • Chang, Y. M., & Luebke, J. I. (2007). Electrophysiological diversity of layer 5 pyramidal cells in the prefrontal cortex of the rhesus monkey: in vitro slice studies. Journal of Neurophysiology, 98(5), 2622–2632.

    Article  PubMed Central  PubMed  Google Scholar 

  • Chang, Y. M., Rosene, D. L., Killiany, R. J., Mangiamele, L. A., & Luebke, J. I. (2005). Increased action potential firing rates of layer 2/3 pyramidal cells in the prefrontal cortex are significantly related to cognitive performance in aged monkeys. Cerebral Cortex, 15, 409–418.

    Article  PubMed  Google Scholar 

  • Constantinidis, C., Franowicz, M. N., & Goldman-Rakic, P. S. (2001). Coding specificity in cortical microcircuits: a multiple-electrode analysis of primate prefrontal cortex. Journal of Neuroscience, 21, 3646–3655.

    CAS  PubMed  Google Scholar 

  • Dickstein, D. L., Kabaso, D., Rocher, A. B., Luebke, J. I., Wearne, S. L., & Hof, P. R. (2007). Changes in the structural complexity of the aged brain. Aging Cell, 6(3), 275–284.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dickstein, D. L., Weaver, C. M., Luebke, J. I., & Hof, P. R. (2013). Dendritic spine changes associated with normal aging. Neuroscience, 22(251), 21–32.

    Article  Google Scholar 

  • Duan, H., Wearne, S. L., Rocher, A. B., Macedo, A., Morrison, J. H., & Hof, P. R. (2003). Age-related dendritic and spine changes in corticocortically projecting neurons in macaque monkeys. Cerebral Cortex, 13(9), 950–961.

    Article  PubMed  Google Scholar 

  • Dumitriu, D., Hao, J., Hara, Y., Kaufmann, J., Janssen, W. G., Lou, W., Rapp, P. R., & Morrison, J. H. (2010). Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment. Journal of Neuroscience, 30(22), 7507–7515.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Edwards, F. A., Konnerth, A., Sakmann, B., & Takahashi, T. (1989). A thin slice preparation for patch clamp recordings from neurones of the mammalian central nervous system. Pflügers Archiv, 414(5), 600–612.

    Article  CAS  PubMed  Google Scholar 

  • Euler, T., & Denk, W. (2001). Dendritic processing. Current Opinion in Neurobiology, 11, 415–422.

    Article  CAS  PubMed  Google Scholar 

  • Faber, E. S. L., & Sah, P. (2003). Calcium-activated potassium channels: Multiple contributions to neuronal function. The Neuroscientist, 9(3), 181–194.

    Article  CAS  PubMed  Google Scholar 

  • Foster, T. C. (2007). Calcium homeostasis and modulation of synaptic plasticity in the aged brain. Aging Cell, 6, 319–325.

    Article  CAS  PubMed  Google Scholar 

  • Fristoe, N. M., Salthouse, T. A., & Woodard, J. L. (1997). Examination of age-related deficits on the Wisconsin Card Sorting Test. Neuropsychology, 11, 428–436.

    Article  CAS  PubMed  Google Scholar 

  • Frolkis, V. V., Martynenko, O. A., & Timchenko, A. N. (1989). Age-related changes in the function of somatic membrane potassium channels of neurons in the mollusc Lymnaea stagnalis. Mechanisms of Ageing and Development, 47(1), 47–54.

    Article  CAS  PubMed  Google Scholar 

  • Fu, Y., Yu, S., Ma, Y., Wang, Y., & Zhou, Y. (2013). Functional degradation of the primary visual cortex during early senescence in rhesus monkeys. Cerebral Cortex, 23(12), 2923–2931.

    Article  PubMed  Google Scholar 

  • Funahashi, S., Bruce, C. J., & Goldman-Rakic, P. S. (1989). Mnemonic coding of visual space in the primate dorsolateral prefrontal cortex. Journal of Neurophysiology, 61, 331–349.

    CAS  PubMed  Google Scholar 

  • Funahashi, S., Bruce, C. J., & Goldman-Rakic, P. S. (1990). Visuospatial coding in primate prefrontal neurons revealed by oculomotor paradigms. Journal of Neurophysiology, 63(4), 814–831.

    CAS  PubMed  Google Scholar 

  • Gallagher, M., & Rapp, P. R. (1997). The use of animal models to study the effects of aging on cognition. Annual Review of Psychology, 48, 339–370.

    Article  CAS  PubMed  Google Scholar 

  • Geisser, S., & Greenhouse, S. W. (1958). An extension of Box's result on the use of the F distribution in multivariate analysis. Annals of Mathematical Statistics, 29, 885–891.

    Article  Google Scholar 

  • Girden, E. R. (1992). ANOVA: repeated measures. Newbury Park: Sage Publications.

    Google Scholar 

  • Goldman-Rakic, P. S. (1995). Cellular basis of working memory. Neuron, 14, 477–485.

    Article  CAS  PubMed  Google Scholar 

  • Hara, Y., Rapp, P. R., & Morrison, J. H. (2012). Neuronal and morphological bases of cognitive decline in aged rhesus monkeys. Age (Dordrecht, Netherlands), 34(5), 1051–1073.

    Article  Google Scholar 

  • Häusser, M., & Mel, B. W. (2003). Dendrites: bug or feature? Current Opinion in Neurobiology, 13(3), 372–383.

    Article  PubMed  Google Scholar 

  • Herndon, J. G., Moss, M. B., Rosene, D., & Killiany, R. J. (1997). Patterns of cognitive decline in aged rhesus monkeys. Behavioural Brain Research, 87, 25–35.

    Article  CAS  PubMed  Google Scholar 

  • Hines, M. L., Morse, T., Migliore, M., Carnevale, N. T., & Shepherd, G. M. (2004). ModelDB: a database to support computational neuroscience. Journal of Computational Neuroscience, 17(1), 7–11.

    Article  PubMed Central  PubMed  Google Scholar 

  • Hodgkin, A. L. (1948). The local electric changes associated with repetitive action in a non-medullated axon. The Journal of Physiology, 107(2), 165–181.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hof, P. R., & Morrison, J. H. (2004). The aging brain: morphomolecular senescence of cortical circuits. Trends in Neurosciences, 27(10), 607–613.

    Article  CAS  PubMed  Google Scholar 

  • Hof, P. R., Duan, H., Page, T. L., Einstein, M., Wicinski, B., He, Y., Erwin, J. M., & Morrison, J. H. (2002). Age-related changes in GluR2 and NMDAR1 glutamate receptor subunit protein immunoreactivity in corticocortically projecting neurons in macaque and patas monkeys. Brain Research, 928(1–2), 175–186.

    Article  CAS  PubMed  Google Scholar 

  • Kabaso, D., Coskren, P. J., Henry, B. I., Hof, P. R., & Wearne, S. L. (2009). The electrotonic structure of pyramidal neurons contributing to prefrontal cortical circuits in macaque monkeys is significantly altered in aging. Cerebral Cortex, 19(10), 2248–2268.

    Article  PubMed Central  PubMed  Google Scholar 

  • Krichmar, J. L., Nasuto, S. J., Scorcioni, R., Washington, S. D., & Ascoli, G. A. (2002). Effects of dendritic morphology on CA3 pyramidal cell electrophysiology: a simulation study. Brain Research, 941, 11–28.

    Article  CAS  PubMed  Google Scholar 

  • Leventhal, A. G., Wang, Y., Pu, M., Zhou, Y., & Ma, Y. (2003). GABA and its agonists improved visual cortical function in senescent monkeys. Science, 300(5620), 812–815.

    Article  CAS  PubMed  Google Scholar 

  • London, M., & Häusser, M. (2005). Dendritic computation. Annual Review of Neuroscience, 28, 503–532.

    Article  CAS  PubMed  Google Scholar 

  • Losonczy, A., Makara, J. K., & Magee, J. C. (2008). Compartmentalized dendritic plasticity and input feature storage in neurons. Nature, 452, 436–441.

    Article  CAS  PubMed  Google Scholar 

  • Luebke, J. I., & Amatrudo, J. M. (2012). Age-related increase of sIAHP in prefrontal pyramidal cells of monkeys: relationship to cognition. Neurobiology of Aging, 33(6), 1085–1095.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Luebke, J. I., Chang, Y. M., Moore, T. L., & Rosene, D. L. (2004). Normal aging results in decreased synaptic excitation and increased synaptic inhibition of layer 2/3 pyramidal cells in the monkey prefrontal cortex. Neuroscience, 125(1), 277–288.

    Article  CAS  PubMed  Google Scholar 

  • Luebke, J. I., Barbas, H., & Peters, A. (2010). Effects of normal aging on prefrontal area 46 in the rhesus monkey. Brain Research Reviews, 62(2), 212–232.

    Article  PubMed Central  PubMed  Google Scholar 

  • Magee, J. C. (2000). Dendritic integration of excitatory synaptic input. Nature Reviews Neuroscience, 1(3), 181–190.

    Article  CAS  PubMed  Google Scholar 

  • Mainen, Z. F., & Sejnowski, T. J. (1996). Influence of dendritic structure on firing patterns in model neocortical neurons. Nature, 382, 363–366.

    Article  CAS  PubMed  Google Scholar 

  • Mainen, Z. F., Joerges, J., Huguenard, J. R., & Sejnowski, T. J. (1995). A model of spike initiation in neocortical pyramidal neurons. Neuron, 15(6), 1427–1439.

    Article  CAS  PubMed  Google Scholar 

  • Marder, E., & Goaillard, J. M. (2006). Variability, compensation and homeostasis in neuron and network function. Nature Reviews Neuroscience, 7(7), 563–574.

    Article  CAS  PubMed  Google Scholar 

  • Migliore, M., & Shepherd, G. M. (2002). Emerging rules for the distributions of active dendritic conductances. Nature Reviews Neuroscience, 3(5), 362–370.

    Article  CAS  PubMed  Google Scholar 

  • Moore, T. L., Killiany, R. J., Herndon, J. G., Rosene, D. L., & Moss, M. B. (2003). Impairment of abstraction and set shifting in aged rhesus monkeys. Neurobiology of Aging, 24, 125–134.

    Article  PubMed  Google Scholar 

  • Morrison, J. H., & Baxter, M. G. (2012). The ageing cortical synapse: hallmarks and implications for cognitive decline. Nature Reviews Neuroscience, 13(4), 240–250.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Niesen, C. E., Baskys, A., & Carlen, P. L. (1988). Reversed ethanol effects on potassium conductances in aged hippocampal dentate granule neurons. Brain Research, 445(1), 137–141.

    Article  CAS  PubMed  Google Scholar 

  • Norenberg, A., Hu, H., Vida, I., Bartos, M., & Jonas, P. (2010). Distinct nonuniform cable properties optimize rapid and efficient activation of fast-spiking GABAergic interneurons. Proceedings of the National Academy of Sciences of the United States of America, 107(2), 894–899.

    Article  PubMed Central  PubMed  Google Scholar 

  • Oh, M. M., Oliveira, F. A., Waters, J., & Disterhoft, J. F. (2013). Altered calcium metabolism in aging CA1 hippocampal pyramidal neurons. Journal of Neuroscience, 33(18), 7905–7911.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Page, T. L., Einstein, M., Duan, H., He, Y., Flores, T., Rolshud, D., Erwin, J. M., Wearne, S. L., Morrison, J. H., & Hof, P. R. (2002). Morphological alterations in neurons forming corticocortical projections in the neocortex of aged patas monkeys. Neuroscience Letters, 317, 37–41.

    Article  CAS  PubMed  Google Scholar 

  • Peters, A. (2002). Structural changes that occur during normal aging of primate cerebral hemispheres. Neuroscience and Biobehavioral Reviews, 26(7), 733–741.

    Article  PubMed  Google Scholar 

  • Porter, N. M., Thibault, O., Thibault, V., Chen, K. C., & Landfield, P. W. (1997). Calcium channel density and hippocampal cell death with age in long-term culture. Journal of Neuroscience, 17(14), 5629–5639.

    CAS  PubMed  Google Scholar 

  • Rinzel, J., & Ermentrout, B. (1998). Analysis of neural excitability and oscillations. In C. Koch & I. Segev (Eds.), Methods in neuronal modeling (2nd ed., pp. 251–291). Cambridge: MIT Press.

    Google Scholar 

  • Rodriguez, A., Ehlenberger, D. B., Hof, P. R., & Wearne, S. L. (2006). Rayburst sampling, an algorithm for automated three-dimensional shape analysis from laser scanning microscopy images. Nature Protocols, 1, 2152–2161.

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez, A., Ehlenberger, D. B., Dickstein, D. L., Hof, P. R., & Wearne, S. L. (2008). Automated three-dimensional detection and shape classification of dendritic spines from fluorescence microscopy images. PLoS One, 3(4), e1997.

    Article  PubMed Central  PubMed  Google Scholar 

  • Rodriguez, A., Ehlenberger, D. B., Hof, P. R., & Wearne, S. L. (2009). Three-dimensional neuron tracing by voxel scooping. Journal of Neuroscience Methods, 184(1), 169–175.

    Article  PubMed Central  PubMed  Google Scholar 

  • Ross, W. N. (2012). Understanding calcium waves and sparks in central neurons. Nature Reviews Neuroscience, 13(3), 157–168.

    CAS  PubMed  Google Scholar 

  • Rumbell, T., Draguljic, D., Luebke, J. I., Hof, P. R., & Weaver, C. M. (2014). Automatic fitness function selection for compartment model optimization. BMC Neuroscience, 15(Suppl 1), O5.

    Article  PubMed Central  Google Scholar 

  • Schaefer, A. T., Larkum, M. E., Sakmann, B., & Roth, A. (2003). Coincidence detection in pyramidal neurons is tuned by their dendritic branching pattern. Journal of Neurophysiology, 89(6), 3143–3154.

    Article  PubMed  Google Scholar 

  • Schmolesky, M. T., Wang, Y., Creel, D. J., & Leventhal, A. G. (2000). Abnormal retinotopic organization of the dorsal lateral geniculate nucleus of the tyrosinase-negative albino cat. The Journal of Comparative Neurology, 427(2), 209–219.

    Article  CAS  PubMed  Google Scholar 

  • Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012). NIH Image to ImageJ: 25 years of image analysis. Nature Methods, 9(7), 671–675.

    Article  CAS  PubMed  Google Scholar 

  • Skinner, F. K. (2013). Moving beyond Type I and Type II neuron types. F1000Res, 2, 19.

  • Stratford, K., Mason, A., Larkman, A., Major, G., & Jack, J. (1989). The modeling of pyramidal neurons in the visual cortex. In R. Durbin, C. Miall, & G. Mitchison (Eds.), The Computing Neuron (pp. 296–321). London: Addison-Wesley.

    Google Scholar 

  • Stuart, G., & Spruston, N. (1998). Determinants of voltage attenuation in neocortical pyramidal neuron dendrites. Journal of Neuroscience, 18(10), 3501–3510.

    CAS  PubMed  Google Scholar 

  • Thibault, O., & Landfield, P. W. (1996). Increase in single L-type calcium channels in hippocampal neurons during aging. Science, 272, 1017–1020.

    Article  CAS  PubMed  Google Scholar 

  • Thibault, O., Hadley, R., & Landfield, P. W. (2001). Elevated postsynaptic [Ca2+]i and L-type calcium channel activity in aged hippocampal neurons: relationship to impaired synaptic plasticity. Journal of Neuroscience, 21, 9744–9756.

    CAS  PubMed  Google Scholar 

  • Thibault, O., Gant, J. C., & Landfield, P. W. (2007). Expansion of the calcium hypothesis of brain aging and Alzheimer's disease: minding the store. Aging Cell, 6(3), 307–317.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Thurbon, D., Luscher, H. R., Hofstetter, T., & Redman, S. J. (1998). Passive electrical properties of ventral horn neurons in rat spinal cord slices. Journal of Neurophysiology, 80(1), 2485–2502.

    CAS  PubMed  Google Scholar 

  • Traub, R. D., Buhl, E. H., Gloveli, T., & Whittington, M. A. (2003). Fast rhythmic bursting can be induced in layer 2/3 cortical neurons by enhancing persistent Na + conductance or by blocking BK channels. Journal of Neurophysiology, 89(2), 909–921.

    Article  CAS  PubMed  Google Scholar 

  • Trevelyan, A. J., & Jack, J. (2002). Detailed passive cable models of layer 2/3 pyramidal cells in rat visual cortex at different temperatures. The Journal of Physiology, 593(2), 623–636.

    Article  Google Scholar 

  • Tsai, K. Y., Carnevale, N. T., Claiborne, B. J., & Brown, T. H. (1994). Efficient mapping from neuroanatomical to electrotonic space. Network, 5, 21–46.

    Article  Google Scholar 

  • van Elburg, R. A., & van Ooyen, A. (2010). Impact of dendritic size and dendritic topology on burst firing in pyramidal cells. PLoS Computational Biology, 6(5), e1000781.

    Article  PubMed Central  PubMed  Google Scholar 

  • Vetter, P., Roth, A., & Hausser, M. (2001). Propagation of action potentials in dendrites depends on dendritic morphology. Journal of Neurophysiology, 85(2), 926–937.

    CAS  PubMed  Google Scholar 

  • Wang, M., Gamo, N. J., Yang, Y., Jin, L. E., Wang, X. J., Laubach, M., Mazer, J. A., Lee, D., & Arnsten, A. F. (2011). Neuronal basis of age-related working memory decline. Nature, 476(7359), 210–213.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wearne, S. L., Rodriguez, A., Ehlenberger, D. B., Rocher, A. B., Henderson, S. C., & Hof, P. R. (2005). New techniques for imaging, digitization and analysis of three-dimensional neural morphology on multiple scales. Neuroscience, 136(3), 661–680.

    Article  CAS  PubMed  Google Scholar 

  • Weaver, C. M., & Wearne, S. L. (2008). Neuronal firing sensitivity to morphologic and active membrane parameters. PLoS Computational Biology, 4, e11.

    Article  PubMed Central  PubMed  Google Scholar 

  • Wilson, I. A., Ikonen, S., Gallagher, M., Eichenbaum, H., & Tanila, H. (2005). Age-associated alterations of hippocampal place cells are subregion specific. Journal of Neuroscience, 25(29), 6877–6886.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, J., Wang, X., Wang, Y., Fu, Y., Liang, Z., Ma, Y., & Leventhal, A. G. (2008). Spatial and temporal sensitivity degradation of primary visual cortical cells in senescent rhesus monkeys. The European Journal of Neuroscience, 28(1), 201–207.

    Article  PubMed  Google Scholar 

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Acknowledgments

Special thanks to Alfredo Rodriguez and Douglas Ehlenberger for development and support of software tools used in 3D reconstructions and morphometric analyses. This work was supported by the National Institutes of Health (grant numbers P01 AG00001, R01 AG025062, R01 AG035071, R01 MH071818, and R01 DC05669).

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The authors declare that they have no conflict of interest.

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Correspondence to Christina M. Weaver.

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Action Editor: Alain Destexhe

We dedicate this article to Susan L. Wearne, our friend, colleague, and mentor, who passed away in September 2009.

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Coskren, P.J., Luebke, J.I., Kabaso, D. et al. Functional consequences of age-related morphologic changes to pyramidal neurons of the rhesus monkey prefrontal cortex. J Comput Neurosci 38, 263–283 (2015). https://doi.org/10.1007/s10827-014-0541-5

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