Anesthetics Rapidly Promote Synaptogenesis during a Critical Period of Brain Development
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{"title"=>"Anesthetics rapidly promote synaptogenesis during a critical period of brain development", "type"=>"journal", "authors"=>[{"first_name"=>"Mathias", "last_name"=>"De Roo", "scopus_author_id"=>"23977796200"}, {"first_name"=>"Paul", "last_name"=>"Klauser", "scopus_author_id"=>"6602359393"}, {"first_name"=>"Adrian", "last_name"=>"Briner", "scopus_author_id"=>"23984085500"}, {"first_name"=>"Irina", "last_name"=>"Nikonenko", "scopus_author_id"=>"6603946961"}, {"first_name"=>"Pablo", "last_name"=>"Mendez", "scopus_author_id"=>"7004193776"}, {"first_name"=>"Alexandre", "last_name"=>"Dayer", "scopus_author_id"=>"15724420800"}, {"first_name"=>"Jozsef Z.", "last_name"=>"Kiss", "scopus_author_id"=>"55663103300"}, {"first_name"=>"Dominique", "last_name"=>"Muller", "scopus_author_id"=>"7403362325"}, {"first_name"=>"Laszlo", "last_name"=>"Vutskits", "scopus_author_id"=>"6602136831"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-70349482096", "sgr"=>"70349482096", "pui"=>"355344504", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"19756154", "doi"=>"10.1371/journal.pone.0007043"}, "id"=>"c1a956f8-fa88-37f7-b10a-5d3248459f8d", "abstract"=>"Experience-driven activity plays an essential role in the development of brain circuitry during critical periods of early postnatal life, a process that depends upon a dynamic balance between excitatory and inhibitory signals. Since general anesthetics are powerful pharmacological modulators of neuronal activity, an important question is whether and how these drugs can affect the development of synaptic networks. To address this issue, we examined here the impact of anesthetics on synapse growth and dynamics. We show that exposure of young rodents to anesthetics that either enhance GABAergic inhibition or block NMDA receptors rapidly induce a significant increase in dendritic spine density in the somatosensory cortex and hippocampus. This effect is developmentally regulated; it is transient but lasts for several days and is also reproduced by selective antagonists of excitatory receptors. Analyses of spine dynamics in hippocampal slice cultures reveals that this effect is mediated through an increased rate of protrusions formation, a better stabilization of newly formed spines, and leads to the formation of functional synapses. Altogether, these findings point to anesthesia as an important modulator of spine dynamics in the developing brain and suggest the existence of a homeostatic process regulating spine formation as a function of neural activity. Importantly, they also raise concern about the potential impact of these drugs on human practice, when applied during critical periods of development in infants.", "link"=>"http://www.mendeley.com/research/anesthetics-rapidly-promote-synaptogenesis-during-critical-period-brain-development", "reader_count"=>55, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Professor > Associate Professor"=>4, "Researcher"=>13, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>2, "Student > Master"=>7, "Other"=>3, "Student > Bachelor"=>2, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Professor > Associate Professor"=>4, "Researcher"=>13, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>2, "Student > Master"=>7, "Other"=>3, "Student > Bachelor"=>2, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>6, "Engineering"=>1, "Agricultural and Biological Sciences"=>27, "Medicine and Dentistry"=>8, "Neuroscience"=>10, "Physics and Astronomy"=>1, "Psychology"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Neuroscience"=>{"Neuroscience"=>10}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>27}, "Unspecified"=>{"Unspecified"=>6}}, "reader_count_by_country"=>{"United States"=>1, "Brazil"=>1, "Australia"=>2, "Switzerland"=>1, "Germany"=>1, "Spain"=>1}, "group_count"=>0}

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  • {"files"=>["https://ndownloader.figshare.com/files/883751"], "description"=>"<p>(a) Maximum intensity projections with 3D volume rendering of confocal images of a CA1 dendrite observed repetitively at 0 h; 5 h and 24 h showing the protrusion turnover in control conditions (left panel) and after midazolam (right panel). +: newly formed protrusions. Scale bar: 1 µm. Hippocampal slices were incubated with midazolam (30 µM) during 5 h just after the first observation (arrow). (b) Protrusion density (expressed as percent of initial values) observed at 0 h, 5 h, 24 h and 48 h in control condition (empty circle) and after midazolam treatment (dark squares). (c) New protrusions per µm detected between 0 to 5 h, or between 24 to 48 h in control conditions (white bars) and after midazolam treatment (dark bars). (d) Same as (c), but for lost protrusions. (e) Number of protrusions per µm that appeared after 1 hour midazolam incubation compared to control conditions. (f) Type of new protrusions for control (ctrl) and midazolam (mida). White bars: spines; gray bars: filopodia. (g) Fraction of spines present at the initial observation (pre-existing spines) still present at 48 h. (h) Fraction of new spines formed between 0 h and 5 h and still present at 48 h. Note that in (g) and (h), only spines were considered: filopodia were excluded because of their very short-term survival. (b–d; f–h): <i>n</i> = 12; 13 cultures for control and midazolam conditions, respectively, 1726 protrusions analyzed. (e): <i>n</i> = 4 cultures for each conditions, 293 protrusions analyzed. (b): 2-way <i>ANOVA</i> with Bonferroni post tests, (c–h): unpaired <i>t</i> tests.</p>", "links"=>[], "tags"=>["midazolam-induced"], "article_id"=>554206, "categories"=>["Medicine", "Developmental Biology", "Neuroscience"], "users"=>["Mathias De Roo", "Paul Klauser", "Adrian Briner", "Irina Nikonenko", "Pablo Méndez", "Alexandre Dayer", "Jozsef Z. Kiss", "Dominique Muller", "Laszlo Vutskits"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007043.g005", "stats"=>{"downloads"=>1, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Spine_dynamics_underlying_midazolam_induced_increase_in_spine_density_/554206", "title"=>"Spine dynamics underlying midazolam-induced increase in spine density.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 04:38:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/883599"], "description"=>"<p>(a) A 5 h midazolam anesthesia is performed at PND 15, protrusion density is measured at PND 20 in one group and at PND 30 in another group. (b) Protrusion head width at PND 20 and PND 30 compared to control groups. (b, c): <i>n</i> = 4 animals per group, 1571 spines; ***: <i>P</i><0.001, *: <i>P</i><0.05, two-way <i>ANOVA</i> with Bonferroni post tests.</p>", "links"=>[], "tags"=>["midazolam", "protrusion", "width", "lasts"], "article_id"=>554049, "categories"=>["Medicine", "Developmental Biology", "Neuroscience"], "users"=>["Mathias De Roo", "Paul Klauser", "Adrian Briner", "Irina Nikonenko", "Pablo Méndez", "Alexandre Dayer", "Jozsef Z. Kiss", "Dominique Muller", "Laszlo Vutskits"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007043.g003", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_midazolam_on_protrusion_density_and_on_head_width_lasts_for_several_days_/554049", "title"=>"Effects of midazolam on protrusion density and on head width lasts for several days.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 04:37:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/883946"], "description"=>"<p>(a) <i>In vivo</i>, intraperitoneal injections of NBQX (30 mg/kg) at PND 15 induced a highly significant increase in protrusion density within 5 hours (<i>n</i> = 617 spines from 3 animals in the control group and 472 spines from 6 animals in the NBQX group). (b) Effects of a 5 h bath incubation of NBQX (20 µM, <i>n</i> = 192 spines in 4 cultures), MK-801 (100 µM, <i>n</i> = 409 protrusions in 8 cultures), or TTX (1 µM, <i>n</i> = 249 protrusions in 5 cultures) on protrusion density compared to control conditions in hippocampal slice cultures (<i>n</i> = 537 protrusions in 10 cultures). (a, b): ***: <i>P</i><0.001, **: <i>P</i><0.01, *: <i>P</i><0.05, unpaired <i>t</i> test.</p>", "links"=>[], "tags"=>["blockade", "ionotropic", "glutamatergic", "receptors", "induce", "protrusion"], "article_id"=>554389, "categories"=>["Medicine", "Developmental Biology", "Neuroscience"], "users"=>["Mathias De Roo", "Paul Klauser", "Adrian Briner", "Irina Nikonenko", "Pablo Méndez", "Alexandre Dayer", "Jozsef Z. Kiss", "Dominique Muller", "Laszlo Vutskits"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007043.g007", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Selective_blockade_of_ionotropic_glutamatergic_receptors_induce_an_increase_in_protrusion_density_/554389", "title"=>"Selective blockade of ionotropic glutamatergic receptors induce an increase in protrusion density.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 04:39:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/883853"], "description"=>"<p>(a) 3D volume rendering of images of an mRFP transfected and Fluo-4 AM loaded cell showing newly formed spines detected 24 h after midazolam application (arrow). The dashed lines and the plain line indicate where line scan analysis was performed at 24 h for the 2 new spines (square and diamond) and a pre-existing spine (star), respectively. (b) Top: line scans of the spines with the corresponding symbols in (a), the red channel showing mRFP fluorescence, and the green channel showing Fluo-4 AM fluorescence. Bottom: Fluo-4 AM corresponding signals expressed as ΔF/F<sub>0</sub>, illustrating the intracellular calcium response obtained upon electrical stimulation of Schaffer collaterals (arrowhead). (c) Percentage of spines that responded to stimulation by an elevation of intracellular free calcium concentration for new (grey) and pre-existing spines (white). (d) Mean amplitude of calcium responses (ΔF/F<sub>0</sub> measured at the peak of the response triggered by electrical stimulation of Schaffer collaterals) for spines present at the beginning of the experiment (pre-existing spines, <i>n</i> = 15 spines in 2 neurons) compared to spines that appeared during of after midazolam treatment (new spines, <i>n</i> = 43 in 4 neurons). <i>P</i> = 0.65, unpaired <i>t</i> test. N-resp.: calcium signal in non responding spines (<i>n</i> = 23 in 4 neurons). (e) Calcium signal of newly formed functional spines before (Functional) and after (Blocked) a half an hour bath application of AP5 (50 µM) and NBQX (20 µM) (<i>n</i> = 8 new spines in 2 cells). Compare to the mean signal recorded for non responding spines in (d). F corresponds to the mean amplitude of the Fluo-4 fluorescence measured during the 20 ms consecutive to the stimulation pulse. Scale bars: (a): 1 µm. (b): 2 s.</p>", "links"=>[], "tags"=>["spines", "formed", "midazolam"], "article_id"=>554305, "categories"=>["Medicine", "Developmental Biology", "Neuroscience"], "users"=>["Mathias De Roo", "Paul Klauser", "Adrian Briner", "Irina Nikonenko", "Pablo Méndez", "Alexandre Dayer", "Jozsef Z. Kiss", "Dominique Muller", "Laszlo Vutskits"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007043.g006", "stats"=>{"downloads"=>3, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_New_spines_formed_following_midazolam_treatment_are_functional_/554305", "title"=>"New spines formed following midazolam treatment are functional.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 04:39:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/883673"], "description"=>"<p>(a) 3D volume rendering of confocal microscopy images of apical dendrites of CA1 hippocampal neurons of PND 15 mice in control (left) and midazolam-anesthetized (right) conditions. Scale bars: 1 µm. (b) Protrusion density of pyramidal neurons of mice sacrificed at PND 15; 20 and 30 just after a 5 h-anesthesia with midazolam (Mida) propofol (Propo) or ketamine (Keta) compared to control conditions (ctrl). (c) protrusion head width in PND 15 mice CA1 neurons after 5 h-midazolam (Mida), propofol (Propo) or Ketamine (Keta) anesthesia compared to control group. (b, c): <i>n</i> = 4 animals per group, 1291 spines; ***: <i>P</i><0.001, *: <i>P</i><0.05, two-way <i>ANOVA</i> with Bonferroni post tests.</p>", "links"=>[], "tags"=>["propofol", "ketamine", "dendritic", "protrusions", "hippocampus"], "article_id"=>554120, "categories"=>["Medicine", "Developmental Biology", "Neuroscience"], "users"=>["Mathias De Roo", "Paul Klauser", "Adrian Briner", "Irina Nikonenko", "Pablo Méndez", "Alexandre Dayer", "Jozsef Z. Kiss", "Dominique Muller", "Laszlo Vutskits"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007043.g004", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_midazolam_propofol_and_ketamine_on_dendritic_protrusions_in_the_hippocampus_in_vivo_/554120", "title"=>"Effects of midazolam, propofol and ketamine on dendritic protrusions in the hippocampus <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 04:38:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/883522"], "description"=>"<p>(a) 3D volume rendering of confocal microscopy images of apical dendrites in control (left), propofol-treated (middle) and ketamine-treated (right) PND 15 mice. Scale bars: 1 µm. (b) Protrusion density of pyramidal neurons of the SCC of mice sacrificed at PND 15; 20 and 30 just after a 5 h-anesthesia with propofol (Propo) or ketamine (Keta) compared to control conditions (ctrl). (c) spine head width at PND 15 after 5 h-propofol (Propo) or Ketamine (Keta) anesthesia compared to control group. (b, c): <i>n</i> = 4 animals per group, 6945 spines; ***: <i>P</i><0.001, **: <i>P</i><0.01, *: <i>P</i><0.05, two-way <i>ANOVA</i> with Bonferroni post tests.</p>", "links"=>[], "tags"=>["propofol", "ketamine", "anesthesia", "dendritic", "protrusions", "somatosensory", "cortex"], "article_id"=>553962, "categories"=>["Medicine", "Developmental Biology", "Neuroscience"], "users"=>["Mathias De Roo", "Paul Klauser", "Adrian Briner", "Irina Nikonenko", "Pablo Méndez", "Alexandre Dayer", "Jozsef Z. Kiss", "Dominique Muller", "Laszlo Vutskits"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007043.g002", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_propofol_and_ketamine_anesthesia_on_dendritic_protrusions_in_the_somatosensory_cortex_in_vivo_/553962", "title"=>"Effects of propofol and ketamine anesthesia on dendritic protrusions in the somatosensory cortex <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 04:37:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/883439"], "description"=>"<p>(a) Representative confocal images (3D volume rendering) showing apical dendritic shafts in control and midazolam-treated animals at PND 15 and PND 30. Scale bar: 5 µm. (b) Protrusion density of pyramidal neurons of the SCC of mice sacrificed at PND 15; 20 and 30 (ctrl; +: P<0.05, Kruskal-Wallis with Dunn post tests). The increase in protrusion density is age-dependent in midazolam injected animals (Mida) compared to control groups (<i>n</i> = 4 animals per group, 4726 protrusions; two-way ANOVA with Bonferroni post tests). (c) Mean dendritic spine head diameter for midazolam-injected (Mida) compared to non-anesthetized mice (Ctrl) at PND 15, 20 and 30 (<i>n</i> = 4 animals per group, 1695 protrusions; ***: <i>P</i><0.001, **: <i>P</i><0.01, two-way <i>ANOVA</i> with Bonferroni post tests). (d–f) Frequency distribution histogram of spine head diameter shows that the effects observed in (b, c) are primarily due to an increase in the number of spines with small heads (each thick mark on x axis is a 0.1 µm interval).</p>", "links"=>[], "tags"=>["increases", "protrusion", "protrusions", "width", "somatosensory", "cortex"], "article_id"=>553870, "categories"=>["Medicine", "Developmental Biology", "Neuroscience"], "users"=>["Mathias De Roo", "Paul Klauser", "Adrian Briner", "Irina Nikonenko", "Pablo Méndez", "Alexandre Dayer", "Jozsef Z. Kiss", "Dominique Muller", "Laszlo Vutskits"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0007043.g001", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Midazolam_increases_protrusion_density_and_reduces_protrusions_head_width_in_the_somatosensory_cortex_in_vivo_/553870", "title"=>"Midazolam increases protrusion density and reduces protrusions head width in the somatosensory cortex <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 04:36:42"}

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  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
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  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
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  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
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  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"15", "full-text"=>"15", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"10", "full-text"=>"12", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"9", "full-text"=>"12", "pdf"=>"33", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
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Relative Metric

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