Alexandra Sachkova

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Alexandra Sachkova
Location Göttingen
Position MD-Student
Tel. +49-(0)551/39-7995

Publications

    • 2022
    • Repetitively burst-spiking neurons in reeler mice show conserved but also highly variable morphological features of layer Vb-fated “thick-tufted” pyramidal cells..
      Jochen F. Staiger*, Alexandra Sachkova, Martin Möck, Julien Guy and Mirko Witte.
      Front. Neuroanat. 16:1000107. doi: 10.3389/fnana.2022.1000107, 2022.
      abstract link

      Reelin is a large extracellular glycoprotein that is secreted by Cajal-Retziuscells during embryonic development to regulate neuronal migration andcell proliferation but it also seems to regulate ion channel distributionand synaptic vesicle release properties of excitatory neurons well intoadulthood. Mousemutants with a compromised reelin signaling cascade showa highly disorganized neocortex but the basic connectional features of thedisplaced excitatory principal cells seem to be relatively intact. Very little isknown, however, about the intrinsic electrophysiological and morphologicalproperties of individual cells in the reeler cortex. Repetitive burst-spiking (RB)is a unique property of large, thick-tufted pyramidal cells of wild-type layer Vbexclusively, which project to several subcortical targets. In addition, they areknown to possess sparse but far-reaching intracortical recurrent collaterals.Here, we compared the electrophysiological properties and morphologicalfeatures of neurons in the reeler primary somatosensory cortex with thoseof wild-type controls. Whereas in wild-type mice, RB pyramidal cells wereonly detected in layer Vb, and the vast majority of reeler RB pyramidal cellswere found in the superficial third of the cortical depth. There were noobvious di􀀀erences in the intrinsic electrophysiological properties and basicmorphological features (such as soma size or the number of dendrites) werealso well preserved. However, the spatial orientation of the entire dendritictree was highly variable in the reeler neocortex, whereas it was completelystereotyped in wild-typemice. It seems that basic quantitative features of layerVb-fated RB pyramidal cells are well conserved in the highly disorganizedmutant neocortex, whereas qualitative morphological features vary, possiblyto properly orient toward the appropriate input pathways, which are knownto show an atypical oblique path through the reeler cortex. The obliquedendritic orientation thus presumably reflects a re-orientation of dendriticinput domains toward spatially highly disorganized a􀀀erent projections.

    • 2016
    • Intracortical Network Effects Preserve Thalamocortical Input Efficacy in a Cortex Without Layers.
      Guy,J.; Sachkova,A.; Möck,M.; Witte,M.; Wagener,R.J.; Staiger,J.F..
      Cerebral Cortex DOI 10.1093/cercor/bhw281, 2016.
      abstract

      Layer IV (LIV) of the rodent somatosensory cortex contains the somatotopic barrel field. Barrels receive much of the sensory input to the cortex through innervation by thalamocortical axons from the ventral posteromedial nucleus. In the reeler mouse, the absence of cortical layers results in the formation of mispositioned barrel-equivalent clusters of LIV fated neurons. Although functional imaging suggests that sensory input activates the cortex, little is known about the cellular and synaptic properties of identified excitatory neurons of the reeler cortex. We examined the properties of thalamic input to spiny stellate (SpS) neurons in the reeler cortex with in vitro electrophysiology, optogenetics, and subcellular channelrhodopsin-2-assisted circuit mapping (sCRACM). Our results indicate that reeler SpS neurons receive direct but weakened input from the thalamus, with a dispersed spatial distribution along the somatodendritic arbor. These results further document subtle alterations in functional connectivity concomitant of absent layering in the reeler mutant. We suggest that intracortical amplification mechanisms compensate for this weakening in order to allow reliable sensory transmission to the mutant neocortex

    • 2012
    • Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex.
      Gentet LJ, Kremer Y, Taniguchi H, Huang ZJ, Staiger J, Petersen CCH.
      Nat Neurosci 15:607-612, 2012.
      abstract link

      Neocortical GABAergic neurons have diverse molecular, structural and electrophysiological features, but the functional correlates of this diversity are largely unknown. We found unique membrane potential dynamics of somatostatin-expressing (SOM) neurons in layer 2/3 of the primary somatosensory barrel cortex of awake behaving mice. SOM neurons were spontaneously active during periods of quiet wakefulness. However, SOM neurons hyperpolarized and reduced action potential firing in response to both passive and active whisker sensing, in contrast with all other recorded types of nearby neurons, which were excited by sensory input. Optogenetic inhibition of SOM neurons increased burst firing in nearby excitatory neurons. We hypothesize that the spontaneous activity of SOM neurons during quiet wakefulness provides a tonic inhibition to the distal dendrites of excitatory pyramidal neurons. Conversely, the inhibition of SOM cells during active cortical processing likely enhances distal dendritic excitability, which may be important for top-down computations and sensorimotor integration.