Activation of parvalbumin-expressing neurons reconfigures neuronal ensembles in murine striatal microcircuits.
ensemble configuration
ensemble sequences
feed-forward inhibition
neuronal ensembles
parvalbumin-expressing neurons
striatal microcircuit
Journal
The European journal of neuroscience
ISSN: 1460-9568
Titre abrégé: Eur J Neurosci
Pays: France
ID NLM: 8918110
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
23
12
2019
received:
18
09
2019
accepted:
02
01
2020
pubmed:
5
1
2020
medline:
30
6
2021
entrez:
5
1
2020
Statut:
ppublish
Résumé
The striatum is the largest entrance to the basal ganglia. Diverse neuron classes make up striatal microcircuit activity, consisting in the sequential activation of neuronal ensembles. How different neuron classes participate in generating ensemble sequences is unknown. In control mus musculus brain slices in vitro, providing excitatory drive generates ensemble sequences. In Parkinsonian microcircuits captured by a highly recurrent ensemble, a cortical stimulus causes a transitory reconfiguration of neuronal groups alleviating Parkinsonism. Alternation between neuronal ensembles needs interconnectivity, in part due to interneurons, preferentially innervated by incoming afferents. One main class of interneuron expresses parvalbumin (PV+ neurons) and mediates feed-forward inhibition. However, its more global actions within the microcircuit are unknown. Using calcium imaging in ex vivo brain slices simultaneously recording dozens of neurons, we aimed to observe the actions of PV+ neurons within the striatal microcircuit. PV+ neurons in active microcircuits are 5%-11% of the active neurons even if, anatomically, they are <1% of the total neuronal population. In resting microcircuits, optogenetic activation of PV+ neurons turns on circuit activity by activating or disinhibiting, more neurons than those actually inhibited, showing that feed-forward inhibition is not their only function. Optostimulation of PV+ neurons in active microcircuits inhibits and activates different neuron sets, resulting in the reconfiguration of neuronal ensembles by changing their functional connections and ensemble membership, showing that neurons may belong to different ensembles at different situations. Our results show that PV+ neurons participate in the mechanisms that generate alternation of neuronal ensembles, therefore provoking ensemble sequences.
Substances chimiques
Parvalbumins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2149-2164Informations de copyright
© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Références
Aparicio-Juárez, A., Duhne, M., Lara-González, E., Ávila-Cascajares, F., Calderón, V., Galarraga, E., & Bargas, J. (2019). Cortical stimulation relieves parkinsonian pathological activity in vitro. European Journal of Neuroscience, 49, 834-848.
Arias-García, M. A., Tapia, D., Laville, J. A., Calderón, V. M., Ramiro-Cortés, Y., Bargas, J., & Galarraga, E. (2018). Functional comparison of corticostriatal and thalamostriatal postsynaptic responses in striatal neurons of the mouse. Brain Structure & Function, 223, 1229-1253.
Assous, M., Faust, T. W., Assini, R., Shah, F., Sidibe, Y., & Tepper, J. M. (2018). Identification and characterization of a novel spontaneously active Bursty GABAergic interneuron in the mouse striatum. Journal of Neuroscience, 38, 5688-5699.
Assous, M., & Tepper, J. M. (2019). Cortical and thalamic inputs exert cell type-specific feedforward inhibition on striatal GABAergic interneurons. Journal of Neuroscience Research. 97, 1491-1502. https://doi.org/10.1002/jnr.24444
Barroso-Flores, J., Herrera-Valdez, M. A., Lopez-Huerta, V. G., Galarraga, E., & Bargas, J. (2015). Diverse short-term dynamics of inhibitory synapses converging on striatal projection neurons: differential changes in a rodent model of Parkinson's disease. Neural Plasticity, 2015, 573543. https://doi.org/10.1155/2015/573543
Beatty, J. A., Song, S. C., & Wilson, C. J. (2015). Cell-type-specific resonances shape the responses of striatal neurons to synaptic input. Journal of Neurophysiology, 113, 688-700.
Berke, J. D. (2008). Uncoordinated firing rate changes of striatal fastspiking interneurons during behavioral task performance. Journal of Neuroscience, 28, 10075-10080.
Berke, J. D. (2011). Functional properties of striatal fast-spiking interneurons. Frontiers in Systems Neuroscience, 5, 45.
Bikoff, J. B., Gabitto, M. I., Rivard, A. F., Drobac, E., Machado, T. A., Miri, A., … Jessell, T. M. (2016). Spinal inhibitory interneuron diversity delineates variant motor microcircuits. Cell, 165, 207-219. https://doi.org/10.1016/j.cell.2016.01.027
Bounova, G., & de Weck, O. (2012). Overview of metrics and their correlation patterns for multiple-metric topology analysis on heterogeneous graph ensembles. Physical Review, 85, 016117.
Burguiére, E., Monteiro, P., Feng, G., & Graybiel, A. M. (2013). Optogenetic stimulation of lateral orbitofronto-striatal pathway suppresses compulsive behaviors. Science, 340, 1243-1246.
Burke, D. A., Rotstein, H. G., & Alvarez, V. A. (2017). Striatal local circuitry: A new framework for lateral inhibition. Neuron, 96, 267-284. https://doi.org/10.1016/j.neuron.2017.09.019
Buzsaki, G. (2010). Neural syntax: Cell assemblies, synapsembles, and readers. Neuron, 68, 362-385. https://doi.org/10.1016/j.neuron.2010.09.023
Calabresi, P., Pisani, A., Mercuri, N. B., & Bernardi, G. (1996). The corticostriatal projection: From synaptic plasticity to dysfunctions of the basal ganglia. Trends in Neurosciences, 19, 19-24.
Carrillo-Reid, L., Hernández-López, S., Tapia, D., Galarraga, E., & Bargas, J. (2011). Dopaminergic modulation of the striatal microcircuit: Receptor-specific configuration of cell assemblies. Journal of Neuroscience, 31, 14972-14983.
Carrillo-Reid, L., Tecuapetla, F., Ibáñez-Sandoval, O., Hernández-Cruz, A., Galarraga, E., & Bargas, J. (2009). Activation of the cholinergic system endows compositional properties to striatal cell assemblies. Journal of Neurophysiology, 101, 737-749.
Carrillo-Reid, L., Tecuapetla, F., Tapia, D., Hernández-Cruz, A., Galarraga, E., Drucker-Colin, R., & Bargas, J. (2008). Encoding network states by striatal cell assemblies. Journal of Neurophysiology, 99, 1435-1450.
Chen, T.-W., Wardill, T. J., Sun, Y., Pulver, S. R., Renninger, S. L., Baohan, A., … Kim, D. S. (2014). Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature, 499, 295-300. https://doi.org/10.1038/nature12354
Choi, K., Holly, E. N., Davatolhagh, M. F., Beier, K. T., & Fuccillo, M. V. (2019). Integrated anatomical and physiological mapping of striatal afferent projections. European Journal of Neuroscience, 49, 626-636.
Chuhma, N., Tanaka, K. F., Hen, R., & Rayport, S. (2011). Functional connectome of the striatal medium spiny neuron. Journal of Neuroscience, 31, 1183-1192.
Committee for the Update of the Guide for the Care and Use of Laboratory Animals, Institute for Laboratory Animal Research, Division on Earth and Life Studies (2011). Guide for the care and use of laboratory animals eighth edition. Washington, D.C.: The National Academies Press. www.nap.edu
Czubayko, U., & Plenz, D. (2002). Fast synaptic transmission between striatal spiny projection neurons. Proceedings of the National Academy of Sciences, 99, 15764-15769.
Dana, H., Mohar, B., Sun, Y., Narayan, S., Gordus, A., Hasseman, J. P., … Kim, D. S. (2016). Sensitive red protein calcium indicators for imaging neural activity. Elife, 5, e12727. https://doi.org/10.7554/eLife.12727
Dobbs, L. K., Kaplan, A. R., Lemos, J. C., Matsui, A., Rubinstein, M., & Alvarez, V. A. (2016). Dopamine regulation of lateral inhibition between striatal neurons gates the stimulant actions of cocaine. Neuron, 90, 1100-1113. https://doi.org/10.1016/j.neuron.2016.04.031
Doig, N. M., Moss, J., & Bolam, J. P. (2010). Cortical and thalamic innervation of direct and indirect pathway medium-sized spiny neurons in mouse striatum. Journal of Neuroscience, 30, 14610-14618.
Flores-Barrera, E., Vizcarra-Chacón, B. J., Bargas, J., Tapia, D., & Galarraga, E. (2011). Dopaminergic modulation of corticostriatal responses in medium spiny projection neurons from direct and indirect pathways. Frontiers in Systems Neuroscience, 5, 15.
Flores-Barrera, E., Vizcarra-Chacón, B. J., Tapia, D., Bargas, J., & Galarraga, E. (2010). Different corticostriatal integration in spiny projection neurons from direct and indirect pathways. Frontiers in Systems Neuroscience, 4, 15.
Fröhlich, F. (2016). Network neuroscience. London, UK: Academic Press-Elsevier.
Garas, F. N., Shah, R. S., Kormann, E., Doig, N. M., Vinciati, F., Nakamura, K. C., … Sharott, A. (2016). Secretagogin expression delineates functionally-specialized populations of striatal parvalbumin-containing interneurons. Elife, 26, 5. https://doi.org/10.7554/eLife.16088
García-Vilchis, B., Suárez, P., Serrano-Reyes, M., Arias-García, M., Tapia, D., Duhne, M., … Galarraga, E. (2019). Differences in synaptic integration between direct and indirect striatal projection neurons: Role of CaV 3 channels. Synapse (New York, N. Y.), 73, e22079.
Gerfen, C. R., & Surmeier, D. J. (2011). Modulation of striatal projection systems by dopamine. Annual Review of Neuroscience, 34, 441-466.
Gittis, A. H., Leventhal, D. K., Fensterheim, B. A., Pettibone, J. R., Berke, J. D., & Kreitzer, A. C. (2011). Selective inhibition of striatal fast-spiking interneurons causes dyskinesias. Journal of Neuroscience, 31, 15727-15731.
Gittis, A. H., Nelson, A. B., Thwin, M. T., Palop, J. J., & Kreitzer, A. C. (2010). Distinct roles of GABAergic interneurons in the regulation of striatal output pathways. Journal of Neuroscience, 30, 2223-2234.
Graveland, G. A., & Difiglia, M. (1985). The frequency and distribution of medium sized neurons with indented nuclei in the primate and rodent neostriatum. Brain Research, 327, 307-311.
Grillner, S., & El Manira, A. (2015). The intrinsic operation of the networks that make us locomote. Current Opinion in Neurobiology, 31, 244-249.
Gritton, H. J., Howe, W. M., Romano, M. F., DiFeliceantonio, A. G., Kramer, M. A., Saligrama, V., … Han, X. (2019). Unique contributions of parvalbumin and cholinergic interneurons in organizing striatal networks during movement. Nature Neuroscience, 22, 586-597.
Guzman, J. N., Hernandez, A., Galarraga, E., Tapia, D., Laville, A., Vergara, R., … Bargas, J. (2003). Dopaminergic modulation of axon collaterals interconnecting spiny neurons of the rat striatum. Journal of Neuroscience, 23, 8931-8940.
Higgs, M. H., & Wilson, C. J. (2019). Frequency-dependent entrainment of striatal fast-spiking interneurons. Journal of Neurophysiology, 122, 1060-1072.
Hippenmeyer, S., Vrieseling, E., Sigrist, M., Portmann, T., Laengle, C., Ladle, D. R., & Arber, S. (2005). A developmental switch in the response of DRG neurons to ETS transcription factor signalling. PloS Biology, 3, 0878-0890.
Humphries, M. D., Wood, R., & Gurney, K. (2009). Dopamine-modulated dynamic cell assemblies generated by the GABAergic striatal microcircuit. Neural Network, 22, 1174-1188.
Ibañez-Sandoval, O., Tecuapetla, F., Unal, B., Shah, F., Koos, T., & Tepper, J. M. (2010). Electrophysiological and morphological characteristics and synaptic connectivity of tyrosine hydroxylase-expressing neurons in adult mouse striatum. Journal of Neuroscience, 30, 6999-7016.
Jáidar, O., Carrillo-Reid, L., Hernández, A., Drucker-Colín, R., Bargas, J., & Hernández-Cruz, A. (2010). Dynamics of the Parkinsonian striatal microcircuit: Entrainment into a dominant network state. Journal of Neuroscience, 30, 11326-11336. https://doi.org/10.1523/JNEUROSCI.1380-10.2010
Jáidar, O., Carrillo-Reid, L., Nakano, Y., Lopez-Huerta, V. G., Hernandez-Cruz, A., Bargas, J., … Arbuthnott, G. W. (2019). Synchronized activation of striatal direct and indirect pathways underlies the behavior in unilateral dopamine-depleted mice. European Journal of Neuroscience, 49, 1512-1528.
Jin, X., Tecuapetla, F., & Costa, R. M. (2014). Basal ganglia subcircuits distinctively encode the parsing and concatenation of action sequences. Nature Neuroscience, 17, 423-430.
Kawaguchi, Y., Wilson, C. J., Augood, S. J., & Emson, P. C. (1995). Striatal interneurons: Chemical, physiological and morphological characterization. Trends in Neurosciences, 18, 527-535.
Kim, D., Jeong, H., Lee, J., Ghim, J. W., Her, E. S., Lee, S. H., & Jung, M. W. (2016). Distinct roles of parvalbumin- and somatostatin-expressing interneurons in working memory. Neuron, 92, 902-915. https://doi.org/10.1016/j.neuron.2016.09.023
Kincaid, A. E., Zheng, T., & Wilson, C. J. (1998). Connectivity and convergence of single corticostriatal axons. Journal of Neuroscience, 18, 47224731.
Kita, H., Kosaka, T., & Heizmann, C. W. (1990). Parvalbumin-immunoreactive neurons in the rat neostriatum: A light and electron microscopic study. Brain Research, 536, 1-15. https://doi.org/10.1016/0006-8993(90)90002-S
Klaus, A., Martins, G. J., Paixao, V. B., Zhou, P., Paninski, L., & Costa, R. M. (2017). The spatiotemporal organization of the striatum encodes action space. Neuron, 95, 1171-1180. https://doi.org/10.1016/j.neuron.2017.08.015
Klug, J. R., Engelhardt, M. D., Cadman, C. N., Li, H., Smith, J. B., Ayala, S., … Jin, X. (2018). Differential inputs to striatal cholinergic and parvalbumin interneurons imply functional distinctions. Elife, 7, e35657.
Koós, T., & Tepper, J. M. (1999). Inhibitory control of neostriatal projection neurons by GABAergic interneurons. Nature Neuroscience, 2, 467-472.
Koós, T., Tepper, J. M., & Wilson, C. J. (2004). Comparison of IPSCs evoked by spiny and fast-spiking neurons in the neostriatum. Journal of Neuroscience, 24, 7916-7922.
Lara-González, E., Duhne, M., Ávila-Cascajares, F., Cruz, S., & Bargas, J. (2019). Comparison of actions between L-DOPA and different dopamine agonists in striatal DA-depleted microcircuits in vitro: Pre-clinical insights. Neuroscience, 410, 76-96. https://doi.org/10.1016/j.neuroscience.2019.04.058
Lee, C. R., Yonk, A. J., Wiskerke, J., Paradiso, K. G., Tepper, J. M., & Margolis, D. J. (2019). Opposing influence of sensory and motor cortical input on striatal circuitry and choice behavior. Current Biology, 29, 1313-1323.
Lee, K., Holley, S. M., Shobe, J. L., Chong, N. C., Cepeda, C., Levine, M. S., & Masmanidis, S. C. (2018). Parvalbumin interneurons modulate striatal output and enhance performance during associative learning. Neuron, 93, 1451-2146. https://doi.org/10.1016/j.neuron.2017.02.033
López-Huerta, V. G., Carrillo-Reid, L., Galarraga, E., Tapia, D., Fiordelisio, T., Drucker-Colin, R., & Bargas, J. (2013). The balance of striatal feedback transmission is disrupted in a model of parkinsonism. Journal of Neuroscience, 33, 4964-4975.
Luk, K. C., & Sadikot, A. F. (2001). GABA promotes survival but not proliferation of parvalbumin-immunoreactive interneurons in rodent neostriatum: An in vivo study with stereology. Neuroscience, 104, 93-103. https://doi.org/10.1016/S0306-4522(01)00038-0
Madisen, L., Zwingman, T. A., Sunkin, S. M., Oh, S. W., Zariwala, H. A., Gu, H., … Zeng, H. (2010). A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nature Neuroscience, 13, 133-140.
Mallet, N., Le Moine, C., Charpier, S., & Gonon, F. (2005). Feedforward inhibition of projection neurons by fast-spiking GABA interneurons in the rat striatum in vivo. Journal of Neuroscience, 25, 3857-3869.
Martiros, N., Burgess, A. A., & Graybiel, A. M. (2018). Inversely active striatal projection neurons and interneurons selectively delimit useful behavioral sequences. Current Biology, 28, 560-573.
Melzer, S., Gil, M., Koser, D. E., Michael, M., Huang, K. W., & Monyer, H. (2017). Distinct corticostriatal GABAergic neurons modulate striatal output neurons and motor activity. Cell Reports, 19, 1045-1055. https://doi.org/10.1016/j.celrep.2017.04.024
Newman, M. E. J. (2003). The structure and function of complex networks. SIAM Review, 45, 167-256.
Oh, S. W., Harris, J. A., Ng, L., Winslow, B., Cain, N., Mihalas, S., … Zeng, H. (2014). A mesoscale connectome of the mouse brain. Nature, 508, 207-214. https://doi.org/10.1038/nature13186
Owen, S. F., Berke, J. D., & Kreitzer, A. C. (2018). Fast-spiking interneurons supply feedforward control of bursting, calcium, and plasticity for efficient learning. Cell, 172, 683-695.e15. https://doi.org/10.1016/j.cell.2018.01.005
Parthasarathy, H. B., & Graybiel, A. M. (1997). Cortically driven immediate-early gene expression reflects modular influence of sensorimotor cortex on identified striatal neurons in the squirrel monkey. Journal of Neuroscience, 17, 2477-2491. https://doi.org/10.1523/JNEUROSCI.17-07-02477.1997
Pérez-Ortega, J., Duhne, M., Lara-González, E., Plata, V., Gasca, D., Galarraga, E., & Bargas, J. (2016). Pathophysiological signatures of functional connectomics in parkinsonian and dyskinetic striatal microcircuits. Neurobiology of Diseases, 91, 347-361.
Planert, H., Szydlowski, S. N., Hjorth, J. J., Grillner, S., & Silberberg, G. (2010). Dynamics of synaptic transmission between fast-spiking interneurons and striatal projection neurons of the direct and indirect pathways. Journal of Neuroscience, 30, 3499-3507.
Ramanathan, S., Hanley, J. J., Deniau, J. M., & Bolam, J. P. (2002). Synaptic convergence of motor and somatosensory cortical afferents onto GABAergic interneurons in the rat striatum. Journal of Neuroscience, 22, 8158-8169. https://doi.org/10.1523/JNEUROSCI.22-18-08158.2002
Rehani, R., Atamna, Y., Tiroshi, L., Chiu, W. H., Aceves Buendía, J. J., Martins, G. J., … Goldberg, J. A. (2019). Activity patterns in the neuropil of striatal cholinergic interneurons in freely moving mice represent their collective spiking Dynamics. eNeuro, 6, pii: ENEURO.0351-18.2018. https://doi.org/10.1523/ENEURO.0351-18.2018
Rendón-Ochoa, E. A., Laville, A., Tapia, D., Cáceres-Chávez, V. A., Hernández-Flores, T., Duhne, M., … Bargas, J. (2018). Calcium currents in striatal fast-spiking interneurons: Dopaminergic modulation of CaV1 channels. BMC Neuroscience, 19, 1-14. https://doi.org/10.1186/s12868-018-0441-0
Roberts, B. M., White, M. G., Patton, M. H., Chen, R., & Mathur, B. N. (2019). Ensemble encoding of action speed by striatal fast-spiking interneurons. Brain Structure & Function, 224, 2567-2576.
Russo, G., Nieus, T. R., Maggi, S., & Taverna, S. (2013). Dynamics of action potential firing in electrically connected striatal fast-spiking interneurons. Frontiers in Cellular Neuroscience, 7, 209.
Rymar, V. V., Sasseville, R., Luk, K. C., & Sadikot, A. F. (2004). Neurogenesis and stereological morphometry of calretinin-immunoreactive GABAergic interneurons of the neostriatum. The Journal of Comparative Neurology, 469, 325-339.
Sciamanna, G., & Wilson, C. J. (2011). The ionic mechanism of gamma resonance in rat striatal fast-spiking neurons. Journal of Neurophysiology, 106, 2936-2949.
Sharott, A., Doig, N. M., Mallet, N., & Magill, P. J. (2012). Relationships between the firing of identified striatal interneurons and spontaneous and driven cortical activities in vivo. Journal of Neuroscience, 32, 13221-13236.
Sheng, M.-J., Lu, D., Shena, Z.-M., & Poo, M.-M. (2019). Emergence of stable striatal D1R and D2R neuronal ensembles with distinct firing sequence during motor learning. Proceedings of the National Academy of Sciences of the United States of America, 16, 11038-11047.
Straub, C., Saulnier, J. L., Begue, A., Feng, D. D., Huang, K. W., & Sabatini, B. L. (2016). Principles of synaptic organization of GABAergic interneurons in the striatum. Neuron, 92, 84-92. https://doi.org/10.1016/j.neuron.2016.09.007
Surmeier, D. J., Carrillo-Reid, L., & Bargas, J. (2011). Dopaminergic modulation of striatal neurons, circuits, and assemblies. Neuroscience, 19, 3-18.
Taverna, S., Canciani, B., & Pennartz, C. M. (2007). Membrane properties and synaptic connectivity of fast-spiking interneurons in rat ventral striatum. Brain Research, 1152, 49-56.
Tecuapetla, F., Carrillo-Reid, L., Bargas, J., & Galarraga, E. (2007). Dopaminergic modulation of short-term synaptic plasticity at striatal inhibitory synapses. Proceedings of the National Academy of Sciences of the United States of America, 104, 10258-10263.
Tecuapetla, F., Jin, X., Lima, S. Q., & Costa, R. M. (2016). Complementary contributions of striatal projection pathways to action initiation and execution. Cell, 166, 703-715. https://doi.org/10.1016/j.cell.2016.06.032
Tecuapetla, F., Koós, T., Tepper, J. M., Kabbani, N., & Yeckel, M. F. (2009). Differential dopaminergic modulation of neostriatal synaptic connections of striatopallidal axon collaterals. Journal of Neuroscience, 29, 8977-8990. https://doi.org/10.1523/JNEUROSCI.6145-08.2009
Tecuapetla, F., Matias, S., Dugue, G. P., Mainen, Z. F., & Costa, R. M. (2014). Balanced activity in basal ganglia projection pathways is critical for contraversive movements. Nature Communications, 5, 4315.
Tepper, J. M., & Bolam, J. P. (2004). Functional diversity and specificity of neostriatal interneurons. Current Opinion in Neurobiology, 14, 685692.
Tepper, J. M., & Koos, T. (2017). Striatal GABAergic interneurons. In H. Steiner, & K. Tseng (Eds.), Handbook of Basal Ganglia Structure and Function 2nd Edition, Handbook of Behavioral Neuroscience, Vol. 24 (pp. 157-178). Cambridge, MA: Academic Press.
Tepper, J. M., Tecuapetla, F., Koos, T., & Ibanñez-Sandoval, O. (2010). Heterogeneity and diversity of striatal GABAergic interneurons. Frontiers in Neuroanatomy, 4, 150.
Tunstall, M. J., Oorschot, D. E., Kean, A., & Wickens, J. R. (2002). Inhibitory interactions between spiny projection neurons in the rat striatum. Journal of Neurophysiology, 88, 1263-1269. https://doi.org/10.1152/jn.2002.88.3.1263
Wu, Y., Richard, S., & Parent, A. (2000). The organization of the striatal output system: A single-cell juxtacellular labeling study in the rat. Neuroscience Research, 38, 49-62. https://doi.org/10.1016/S0168-0102(00)00140-1
Xu, M., Li, L., & Pittenger, C. (2016). Ablation of fast-spiking interneurons in the dorsal striatum, recapitulating abnormalities seen post-mortem in Tourette syndrome, produces anxiety and elevated grooming. Journal of Neuroscience, 324, 321-329. https://doi.org/10.1016/j.neuroscience.2016.02.074