Hilar Somatostatin Interneurons Contribute to Synchronized GABA Activity in an In Vitro Epilepsy Model
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{"title"=>"Hilar somatostatin interneurons contribute to synchronized GABA activity in an in vitro epilepsy model", "type"=>"journal", "authors"=>[{"first_name"=>"Sabine", "last_name"=>"Grosser", "scopus_author_id"=>"56355128500"}, {"first_name"=>"Bridget N.", "last_name"=>"Queenan", "scopus_author_id"=>"55792559800"}, {"first_name"=>"Rupa R.", "last_name"=>"Lalchandani", "scopus_author_id"=>"55782402200"}, {"first_name"=>"Stefano", "last_name"=>"Vicini", "scopus_author_id"=>"7005632078"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"372852691", "doi"=>"10.1371/journal.pone.0086250", "sgr"=>"84907029476", "scopus"=>"2-s2.0-84907029476", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"24465989"}, "id"=>"f881cf38-2349-3c43-89bb-c2c82769a01b", "abstract"=>"Epilepsy is a disorder characterized by excessive synchronized neural activity. The hippocampus and surrounding temporal lobe structures appear particularly sensitive to epileptiform activity. Somatostatin (SST)-positive interneurons within the hilar region have been suggested to gate hippocampal activity, and therefore may play a crucial role in the dysregulation of hippocampal activity. In this study, we examined SST interneuron activity in the in vitro 4-aminopyridine (4-AP) model of epilepsy. We employed a multi-disciplinary approach, combining extracellular multi-electrode array (MEA) recordings with patch-clamp recordings and optical imaging using a genetically encoded calcium sensor. We observed that hilar SST interneurons are strongly synchronized during 4-AP-induced local field potentials (LFPs), as assayed by Ca(2+) imaging as well as juxtacellular or intracellular recording. SST interneurons were particularly responsive to GABA-mediated LFPs that occurred in the absence of ionotropic glutamatergic transmission. Our results present evidence that the extensive synchronized activity of SST-expressing interneurons contribute to the generation of GABAergic LFPs in an in vitro model of temporal lobe seizures.", "link"=>"http://www.mendeley.com/research/hilar-somatostatin-interneurons-contribute-synchronized-gaba-activity-vitro-epilepsy-model", "reader_count"=>32, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>6, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Student > Master"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>1, "Researcher"=>6, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Student > Master"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>5, "Neuroscience"=>8, "Psychology"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Neuroscience"=>{"Neuroscience"=>8}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"United States"=>2, "Japan"=>1, "United Kingdom"=>1, "Chile"=>1, "France"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1352836"], "description"=>"<p>GCaMP3 fluorescence (orange) recorded simultaneously with extracellular LFPs (A1) during juxtacellular (A2, red) and intracellular current-clamp (A3, blue) recording from two SST- interneurons. The depolarization and spike burst duration were longer in correspondence to the LFP<sub>P-CA3/DG</sub> than to the LFP<sub>R-CA3</sub> (A). Perfusion with CPP/NBQX (<b>B</b>) induced sustained spiking of the SST- interneuron with juxtacellular recording, but not for the SST-interneuron recorded in current clamp mode (resting membrane potential = −67 mV). Note the biphasic Ca<sup>2+</sup> transient in cell #1 during CPP/NBQX application.</p>", "links"=>[], "tags"=>["biotechnology", "Genetic engineering", "transgenics", "Model organisms", "Animal models", "mouse", "neuroscience", "neurophysiology", "synapses", "Cellular neuroscience", "neural networks", "Anatomy and physiology", "Neurological system", "neurology", "epilepsy", "Neuropharmacology", "evoke", "spontaneous", "epsps", "synchronous", "depolarization", "sst-"], "article_id"=>905325, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sabine Grosser", "Bridget N. Queenan", "Rupa R. Lalchandani", "Stefano Vicini"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086250.g005", "stats"=>{"downloads"=>2, "page_views"=>47, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LFPs_evoke_spontaneous_EPSPs_with_a_large_synchronous_depolarization_in_SST_interneurons_/905325", "title"=>"LFPs evoke spontaneous EPSPs with a large synchronous depolarization in SST- interneurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-21 03:05:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352831"], "description"=>"<p>(<b>A</b>) Representative images of GCaMP3 signal in a visual field containing several SST interneurons before (left) and during (right) LFP<sub>P-CA3/DG</sub>. (B) Simultaneous optical (B1) and juxtacellular (B3) recordings of SST activity during hippocampal LFPs (B2). B1: Fluorescent Ca<sup>2+</sup> signals (ΔF/F) recorded from the ROIs indicated in (<b>A</b>). B2: Distinct LFPs recorded from pMEA electrodes located in the DG (black) and the CA3 (grey) regions.B3: Simultaneously recorded juxtacellular trace from a visually identified SST interneuron. (<b>C</b>) Same recording configuration as in (<b>B</b>) in the presence of the iGlurR antagonists, CPP and NBQX. Sections of traces in B3 and C3 (dotted line) are expanded below.</p>", "links"=>[], "tags"=>["biotechnology", "Genetic engineering", "transgenics", "Model organisms", "Animal models", "mouse", "neuroscience", "neurophysiology", "synapses", "Cellular neuroscience", "neural networks", "Anatomy and physiology", "Neurological system", "neurology", "epilepsy", "Neuropharmacology", "lfps", "ap", "firing"], "article_id"=>905320, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sabine Grosser", "Bridget N. Queenan", "Rupa R. Lalchandani", "Stefano Vicini"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086250.g003", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_4_AP_induced_LFPs_provoke_AP_firing_from_SST_interneurons_/905320", "title"=>"4-AP-induced LFPs provoke AP firing from SST-interneurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-21 03:05:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352838"], "description"=>"<p>(A) Extracellular pMEA recording of LFPs (A1) together with concurrent optical imaging (A2) and juxtacellular (A3) or voltage-clamp (A4) recording (Vh = −50 mV, holding current 45 pA) from two SST- interneurons. The inward currents observed were significantly longer and larger in correspondence to the LFP<sub>P-CA3/DG</sub> than to the LFP<sub>R-CA3</sub>. Perfusion with NBQX/CPP (<b>B</b>) abolished the excitatory current revealing the occurrence of sustained IPSCs in association to the CPP/NBQX LFP. Note the increase in spontaneous IPSCs during the time between the LFPs occurrence. (<b>C</b>) Voltage-clamp recording (Vh = −52 mV, holding current 37 pA) from another SST- interneuron shown at different time scales illustrating the occurrence of inward EPSCs and less frequent outward IPSCs. Perfusion with NBQX/CPP (<b>D</b>) in the same neurons abolishes all EPSCs and reveals the occurrence of IPSCs.</p>", "links"=>[], "tags"=>["biotechnology", "Genetic engineering", "transgenics", "Model organisms", "Animal models", "mouse", "neuroscience", "neurophysiology", "synapses", "Cellular neuroscience", "neural networks", "Anatomy and physiology", "Neurological system", "neurology", "epilepsy", "Neuropharmacology", "recordings", "lfp-induced", "currents", "sst-"], "article_id"=>905327, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sabine Grosser", "Bridget N. Queenan", "Rupa R. Lalchandani", "Stefano Vicini"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086250.g006", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Voltage_clamp_recordings_of_LFP_induced_currents_in_SST_interneurons_/905327", "title"=>"Voltage-clamp recordings of LFP-induced currents in SST- interneurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-21 03:05:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352834"], "description"=>"<p>(A) Fluorescence image of GCaMP3-expressing SST interneurons before (left) and during a CPP/NBQX LFP (right). (B) Top: LFPs recorded in the presence of CPP/NBQX. Bottom: Ca<sup>2+</sup> transients (ΔF/F) recorded from SST- interneurons in the presence of CPP/NBQX. Average change in ΔF/F triggered by the CPP/NBQX LFP reveals two distinct types of changes in Ca<sup>2+</sup> transient in SST- interneurons. (C) Representative Ca<sup>2+</sup> transients in three groups of SST- interneurons. Distinct monophasic (grey), intermediate (red) and biphasic (brown) Ca<sup>2+</sup> transient are observed from SST- interneurons in response to CPP/NBQX LFPs recorded in DG and CA3 (top).</p>", "links"=>[], "tags"=>["biotechnology", "Genetic engineering", "transgenics", "Model organisms", "Animal models", "mouse", "neuroscience", "neurophysiology", "synapses", "Cellular neuroscience", "neural networks", "Anatomy and physiology", "Neurological system", "neurology", "epilepsy", "Neuropharmacology", "gcamp3", "fluorescence", "sst", "interneurons", "4-ap", "induced"], "article_id"=>905323, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sabine Grosser", "Bridget N. Queenan", "Rupa R. Lalchandani", "Stefano Vicini"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086250.g004", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Variability_of_the_GCaMP3_fluorescence_response_in_SST_interneurons_during_4_AP_induced_LFPs_/905323", "title"=>"Variability of the GCaMP3 fluorescence response in SST interneurons during 4-AP induced LFPs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-21 03:05:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352828"], "description"=>"<p>Representative recordings of 4-AP-induced LFPs (A1,B1) and SST interneuron firing (A2,B2) during epileptiform activity. 4-AP provoked two classes of LFPs, detectable in CA3 (gray) and DG (black) hippocampal regions via extracellular pMEA recording (A1,B1): LFP<sub>R-CA3</sub> and LFP<sub>P-CA3/DG</sub> (indicated with *). Juxtacellular patch-clamp recordings (A2,B2) from two visually identified SST- interneurons demonstrate increased AP firing of SST-interneurons in correspondence to distinct LFPs. Sections of the traces in <b>A</b> are shown at an expanded time scale in panel <b>B</b>.</p>", "links"=>[], "tags"=>["biotechnology", "Genetic engineering", "transgenics", "Model organisms", "Animal models", "mouse", "neuroscience", "neurophysiology", "synapses", "Cellular neuroscience", "neural networks", "Anatomy and physiology", "Neurological system", "neurology", "epilepsy", "Neuropharmacology", "sst", "interneurons", "4-ap", "induced"], "article_id"=>905317, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sabine Grosser", "Bridget N. Queenan", "Rupa R. Lalchandani", "Stefano Vicini"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086250.g002", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Firing_of_SST_interneurons_during_4_AP_induced_LFPs_/905317", "title"=>"Firing of SST interneurons during 4-AP induced LFPs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-21 03:05:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352825"], "description"=>"<p>Representative fluorescence micrographs (Z-projection of confocal stacks) illustrating the expression of td-Tomato (<b>A</b>) and GCaMP3 (<b>B</b>) in the hippocampal hilus of SST-Ires-Cre reporter mice (postnatal days 18 and 14, respectively). GCaMP3 imaging was performed in the presence of 40 mM KCl to achieve maximal activation of the Ca<sup>2+</sup> sensor.</p>", "links"=>[], "tags"=>["biotechnology", "Genetic engineering", "transgenics", "Model organisms", "Animal models", "mouse", "neuroscience", "neurophysiology", "synapses", "Cellular neuroscience", "neural networks", "Anatomy and physiology", "Neurological system", "neurology", "epilepsy", "Neuropharmacology", "somatostatin-positive", "interneurons", "hilus", "sst-ires-cre"], "article_id"=>905313, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Sabine Grosser", "Bridget N. Queenan", "Rupa R. Lalchandani", "Stefano Vicini"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086250.g001", "stats"=>{"downloads"=>8, "page_views"=>31, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_somatostatin_positive_interneurons_in_the_hilus_of_SST_Ires_Cre_mice_/905313", "title"=>"Distribution of somatostatin-positive interneurons in the hilus of SST-Ires-Cre mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-21 03:05:16"}

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