Spatial distribution of neurons innervated by chandelier cells
Lidia Blazquez-Llorca
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Alan Woodruff
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Melis Inan
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Stewart A. Anderson
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Rafael Yuste
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Javier DeFelipe
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Angel Merchan-Perez
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L. Blazquez-Llorca J. DeFelipe Instituto Cajal
, CSIC,
Madrid, Spain
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L. Blazquez-Llorca J. DeFelipe A. Merchan-Perez (&) Laboratorio Cajal de Circuitos Corticales (CTB),
Universidad Politecnica de Madrid
,
Madrid, Spain
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Axo-axonic cell Pyramidal GABA Three-dimensional
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A. Merchan-Perez DATSI,
Universidad Politecnica de Madrid
,
Madrid, Spain
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S. A. Anderson Department of Psychiatry, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine
,
Philadelphia, PA 19104, USA
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M. Inan Brain and Mind Research Institute, Weill Cornell Medical College
,
New York, NY 10065, USA
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A. Woodruff R. Yuste Department of Biological Sciences, Columbia University
,
New York, NY, USA
Chandelier (or axo-axonic) cells are a distinct group of GABAergic interneurons that innervate the axon initial segments of pyramidal cells and are thus thought to have an important role in controlling the activity of cortical circuits. To examine the circuit connectivity of chandelier cells (ChCs), we made use of a genetic targeting strategy to label neocortical ChCs in upper layers of juvenile mouse neocortex. We filled individual ChCs with biocytin in living brain slices and reconstructed their axonal arbors from serial semi-thin sections. We also reconstructed the cell somata of pyramidal neurons that were located inside the ChC axonal trees and determined the percentage of pyramidal neurons whose axon initial segments were innervated by ChC terminals. We found that the total percentage of pyramidal neurons that were innervated by a single labeled ChC was 18-22 %. Sholl analysis showed that this percentage peaked at 22-35 % for distances between 30 and 60 lm from the ChC soma, decreasing to lower percentages with increasing distances. We also studied the three-dimensional spatial distribution of the innervated neurons inside the ChC axonal arbor using spatial statistical analysis tools. We found that innervated pyramidal neurons are not distributed at random, but show a clustered distribution, with pockets where almost all cells are innervated and other regions within the ChC axonal tree that receive little or no innervation. Thus, individual ChCs may exert a strong, widespread influence on their local pyramidal neighbors in a spatially heterogeneous fashion.
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The GABA (c-aminobutyric acid)-ergic interneurons of the
cerebral cortex are a diverse population of cells. Their
diversity is manifested in every aspect of their phenotype,
as evidenced by their many different morphological,
electrophysiological and neurochemical features. Different
subtypes of cortical interneurons target different
subcellular compartments of the postsynaptic neurons such that
there are neurons that innervate only the axon initial
segment (AIS), whereas others innervate mainly dendrites or
both dendrites and somata with different degrees of
selectivity (Ascoli et al. 2008).
Moreover, it has been suggested that in general
GABAergic interneurons are not selective for a particular type of
neuron (Sohya et al. 2007; Niell and Stryker 2008; Liu
et al. 2009) with spatial proximity being the predictor of
their connectivity (Bock et al. 2011). A similar conclusion
has been reached from examination of connections with
those pyramidal neurons located within the axonal arbors
of certain subpopulations of GABAergic cells, such as
somatostatin-positive (Fino and Yuste 2011; Packer et al.
2013) and parvalbumin-positive neurons (Packer and Yuste
2011; Packer et al. 2013). However, the connections
between GABAergic interneurons seem to be more
selective. For example, it has been shown that the three major,
molecularly distinct interneuron populationsnamely,
parvalbumin-, somatostatin- and vasoactive intestinal
peptide-expressing interneuronsclearly differ in terms of
the connections between one another (Pfeffer et al. 2013):
parvalbumin-expressing interneurons mainly inhibit one
another, whereas somatostatin-expressing interneurons
inhibit parvalbumin- and vasoactive intestinal
peptideexpressing interneurons and apparently do not inhibit one
another. Meanwhile, vasoactive intestinal
peptideexpressing interneurons preferentially inhibit
somatostatinexpressing interneurons.
Nevertheless, there are many different subtypes of
inhibitory cells with widely different anatomical and
physiological properties and connectivity patterns (Ascoli
et al. 2008) and it is therefore possible that distinct
subtypes of cortical GABAergic interneurons may differ in
their selectivity for their targets. Thus, identifying classes
and subclasses of interneurons is an important step towards
understanding how inhibition shapes cortical function
(Ascoli et al. 2008; Kepecs and Fishell 2014).
Chandelier cells (ChCs), also known as axo-axonic
cells, are among t (...truncated)