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@PHDTHESIS{Yang:749817,
      author       = {Yang, Danqing},
      othercontributors = {Feldmeyer, Dirk and Kampa, Björn Michael},
      title        = {{C}haracterization of synaptic connections and cholinergic
                      modulation of layer 6{A} microcircuitry in rat barrel
                      cortex},
      school       = {RWTH Aachen University},
      type         = {Dissertation},
      address      = {Aachen},
      reportid     = {RWTH-2018-230346},
      pages        = {1 Online-Ressource (109 Seiten) : Illustrationen,
                      Diagramme},
      year         = {2018},
      note         = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
                      University 2019; Dissertation, RWTH Aachen University, 2018},
      abstract     = {Of all neocortical layers, layer 6 is the least studied
                      layer that shows a relatively high neuronalheterogeneity and
                      low intralaminar connectivity. Layer 6A provides direct
                      projections from corticothalamic(CT) pyramidal cells to both
                      VPM and POM nucleus of the thalamus and are thus integral
                      part of a thalamo-cortical-thalamic feedback loop that
                      controls sensory signalling. In this study, we investigated
                      anatomical and functional properties of L6A intra-laminar
                      excitatory and inhibitory connections in L6A of rat barrel
                      cortex by performing dual whole-cell recordings with
                      simultaneousbiocytin fillings. The neuronal morphology was
                      subsequently reconstructed and putative CT
                      andcortico-cortical (CC) pyramidal cells were distinguished
                      based on their distinct axonal projection patterns. An
                      unsupervised cluster analysis were performed to classify FS
                      and nFS interneurons based on their electrophysiological
                      properties such as membrane properties and firing
                      properties. Thus, different types of connections were
                      identified based on pre- and postsynaptic neuronalsubtypes.
                      The intralaminar connectivity of L6A neurons is low with a
                      connectivity ratio of $6.5\%$ (n=79).There is a much higher
                      probability of a CC-like rather than a CT-like pyramidal
                      cell being presynaptic as well as postsynaptic. In response
                      to presynaptic APs elicited in CT-like pyramidal cells,
                      EPSPs showed remarkably smaller amplitude, larger PPR, CV
                      and failure rate recorded than those elicited by presynaptic
                      APs in CC L6A pyramidal cells. For excitatory-inhibitory
                      connections between CC cells and interneurons, FS and non-FS
                      interneuron exhibited short-term depression and
                      facilitation, respectively; while for connections between CT
                      cells and interneurons, facilitated EPSPs were observed
                      regardless of interneuron type. Moreover, we found that FS
                      interneurons trigger a ‘fast’ postsynaptic response with
                      short rise time and latency in excitatory neurons, whereas
                      nFS interneurons display ‘slow’ kinetics by generating
                      IPSPs with significantly longer rise time and latency.
                      Notably, reciprocal connections were found only between two
                      CC-like pyramidal cells orCC-interneurons, but not for
                      connections involving a CT pyramidal cell. Acetylcholine
                      (ACh) is released from the basal forebrain during different
                      behavioural states, e.g. wakefulness and attention and
                      differentially modulates neocortical neurons via both
                      nicotinic and muscarinic ACh receptors. Here we investigated
                      the cholinergic modulation of CT and CCpyramidal cells in
                      layer 6A of the barrel cortex. We found that ACh
                      differentially modulates theL6A microcircuitry by
                      persistently depolarizing CT but hyperpolarizing CC L6A
                      pyramidal cells, effects that are concentration-dependent
                      and are mediated via M1 and M4 mAChRs, respectively. ACh
                      application increases frequency of miniature EPSCs via
                      presynaptic nAChRs in L6A CT but not CC pyramidal cells. To
                      better understand the effects of ACh on intralaminar
                      synaptictrans mission, recordings were performed from
                      synaptically coupled L6A pyramidal cell pairs. We found that
                      ACh suppresses presynaptic release in neuronal microcircuits
                      with a presynaptic CCpyramidal cell via activation of M4Rs.
                      In marked contrast, ACh increased the release probability
                      inL6A connections with a presynaptic CT neuron through
                      activating nAChRs. Our results reveal that two functionally
                      and morphologically distinct subpopulations of L6A pyramidal
                      cells are affected differentially by ACh indicating that
                      intra- and subcortical signaling is subject to behavioural
                      modulation.},
      cin          = {535500-2 / 162320 / 160000},
      ddc          = {570},
      cid          = {$I:(DE-82)535500-2_20140620$ / $I:(DE-82)162320_20140620$ /
                      $I:(DE-82)160000_20140620$},
      typ          = {PUB:(DE-HGF)11},
      doi          = {10.18154/RWTH-2018-230346},
      url          = {https://publications.rwth-aachen.de/record/749817},
}