Enhanced long-term microcircuit plasticity in the valproic Acid animal model of autism.
Identifieur interne : 000119 ( PubMed/Checkpoint ); précédent : 000118; suivant : 000120Enhanced long-term microcircuit plasticity in the valproic Acid animal model of autism.
Auteurs : Guilherme Testa Silva [Suisse] ; Jean-Vincent Le Bé ; Imad Riachi ; Tania Rinaldi ; Kamila Markram ; Henry MarkramSource :
- Frontiers in synaptic neuroscience [ 1663-3563 ] ; 2009.
Abstract
A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a minicolumn (<50 μm). In the present study, we explored whether Long Term Microcircuit Plasticity (LTMP) was altered in this animal model. We performed multi-neuron patch-clamp recordings on clusters of layer 5 pyramidal cells in somatosensory cortex brain slices (PN 12-15), mapped the connectivity and characterized the synaptic properties for connected neurons. Pipettes were then withdrawn and the slice was perfused with 100 μM sodium glutamate in artificial cerebrospinal fluid in the recording chamber for 12 h. When we re-patched the same cluster of neurons, we found enhanced LTMP only at inter-somatic distances beyond minicolumnar dimensions. These data suggest that hyperconnectivity is already near its peak within the dimensions of the minicolumn in the treated animals and that LTMP, which is normally restricted to within a minicolumn, spills over to drive hyperconnectivity across the dimensions of a minicolumn. This study provides further evidence to support the notion that the neocortex is highly plastic in response to new experiences in this animal model of autism.
DOI: 10.3389/neuro.19.001.2009
PubMed: 21423407
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Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a minicolumn (<50 μm). In the present study, we explored whether Long Term Microcircuit Plasticity (LTMP) was altered in this animal model. We performed multi-neuron patch-clamp recordings on clusters of layer 5 pyramidal cells in somatosensory cortex brain slices (PN 12-15), mapped the connectivity and characterized the synaptic properties for connected neurons. Pipettes were then withdrawn and the slice was perfused with 100 μM sodium glutamate in artificial cerebrospinal fluid in the recording chamber for 12 h. When we re-patched the same cluster of neurons, we found enhanced LTMP only at inter-somatic distances beyond minicolumnar dimensions. These data suggest that hyperconnectivity is already near its peak within the dimensions of the minicolumn in the treated animals and that LTMP, which is normally restricted to within a minicolumn, spills over to drive hyperconnectivity across the dimensions of a minicolumn. This study provides further evidence to support the notion that the neocortex is highly plastic in response to new experiences in this animal model of autism.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="PubMed-not-MEDLINE"><PMID Version="1">21423407</PMID><DateCreated><Year>2011</Year><Month>03</Month><Day>22</Day></DateCreated><DateCompleted><Year>2011</Year><Month>07</Month><Day>14</Day></DateCompleted><DateRevised><Year>2013</Year><Month>08</Month><Day>13</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1663-3563</ISSN><JournalIssue CitedMedium="Print"><Volume>1</Volume><PubDate><Year>2009</Year></PubDate></JournalIssue><Title>Frontiers in synaptic neuroscience</Title><ISOAbbreviation>Front Synaptic Neurosci</ISOAbbreviation></Journal><ArticleTitle>Enhanced long-term microcircuit plasticity in the valproic Acid animal model of autism.</ArticleTitle><Pagination><MedlinePgn>1</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3389/neuro.19.001.2009</ELocationID><Abstract><AbstractText>A single intra-peritoneal injection of valproic acid (VPA) on embryonic day (ED) 11.5 to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. Previous studies showed that the microcircuitry is hyperreactive due to hyperconnectivity of glutamatergic synapses and hyperplastic due to over-expression of NMDA receptors. These changes were restricted to the dimensions of a minicolumn (<50 μm). In the present study, we explored whether Long Term Microcircuit Plasticity (LTMP) was altered in this animal model. We performed multi-neuron patch-clamp recordings on clusters of layer 5 pyramidal cells in somatosensory cortex brain slices (PN 12-15), mapped the connectivity and characterized the synaptic properties for connected neurons. Pipettes were then withdrawn and the slice was perfused with 100 μM sodium glutamate in artificial cerebrospinal fluid in the recording chamber for 12 h. When we re-patched the same cluster of neurons, we found enhanced LTMP only at inter-somatic distances beyond minicolumnar dimensions. These data suggest that hyperconnectivity is already near its peak within the dimensions of the minicolumn in the treated animals and that LTMP, which is normally restricted to within a minicolumn, spills over to drive hyperconnectivity across the dimensions of a minicolumn. This study provides further evidence to support the notion that the neocortex is highly plastic in response to new experiences in this animal model of autism.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Silva</LastName><ForeName>Guilherme Testa</ForeName><Initials>GT</Initials><AffiliationInfo><Affiliation>Laboratory of Neural Microcircuitry, Brain and Mind Institute, EPFL Lausanne, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Le Bé</LastName><ForeName>Jean-Vincent</ForeName><Initials>JV</Initials></Author><Author ValidYN="Y"><LastName>Riachi</LastName><ForeName>Imad</ForeName><Initials>I</Initials></Author><Author ValidYN="Y"><LastName>Rinaldi</LastName><ForeName>Tania</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Markram</LastName><ForeName>Kamila</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Markram</LastName><ForeName>Henry</ForeName><Initials>H</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2009</Year><Month>06</Month><Day>24</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Synaptic Neurosci</MedlineTA><NlmUniqueID>101548972</NlmUniqueID><ISSNLinking>1663-3563</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>J Neurosci. 2003 Oct 22;23(29):9565-74</RefSource><PMID Version="1">14573536</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Eur Child Adolesc Psychiatry. 2001 Mar;10(1):58-66</RefSource><PMID Version="1">11315537</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Genes Brain Behav. 2003 Oct;2(5):255-67</RefSource><PMID 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IdType="pmc">PMC3059606</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Suisse</li></country></list><tree><noCountry><name sortKey="Le Be, Jean Vincent" sort="Le Be, Jean Vincent" uniqKey="Le Be J" first="Jean-Vincent" last="Le Bé">Jean-Vincent Le Bé</name><name sortKey="Markram, Henry" sort="Markram, Henry" uniqKey="Markram H" first="Henry" last="Markram">Henry Markram</name><name sortKey="Markram, Kamila" sort="Markram, Kamila" uniqKey="Markram K" first="Kamila" last="Markram">Kamila Markram</name><name sortKey="Riachi, Imad" sort="Riachi, Imad" uniqKey="Riachi I" first="Imad" last="Riachi">Imad Riachi</name><name sortKey="Rinaldi, Tania" sort="Rinaldi, Tania" uniqKey="Rinaldi T" first="Tania" last="Rinaldi">Tania Rinaldi</name></noCountry><country name="Suisse"><noRegion><name sortKey="Silva, Guilherme Testa" sort="Silva, Guilherme Testa" uniqKey="Silva G" first="Guilherme Testa" last="Silva">Guilherme Testa 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