Elsevier

Neuroscience

Volume 404, 15 April 2019, Pages 268-281
Neuroscience

Research Article
Two Groups of eGFP-Expressing Neurons with Distinct Characteristics in the Neocortex of GIN Mice

https://doi.org/10.1016/j.neuroscience.2019.01.026Get rights and content

Highlights

  • •

    A new group of eGFP+ neurons, in addition to the previously reported one, is present in the neocortex of GIN mice.

  • •

    Those eGFP+ neurons are distributed in the deep cortical layers as clusters and disappear mostly after the second postnatal month.

  • •

    They are not immunoreactive for SST, PV, GAD, and CaMKII antibodies.

  • •

    They display distinct intrinsic and synaptic properties and postnatal development.

Abstract

GIN (GFP-expressing inhibitory interneuron) transgenic mice are believed to express the enhanced GFP (eGFP) in a subset of somatostatin (SST)-expressing interneurons in the neocortex and have been widely used in the study on SST interneurons. Previous studies showed that eGFP+ neurons in the neocortex are distributed in the layer II-IV and upper layer V (cortical eGFP neurons) and contain SST. In this study, we reported a new group of eGFP+ neurons in GIN mice at early postnatal ages, which was located in the deep layer of the lateral neocortex as clusters (cluster eGFP neurons). Cluster eGFP neurons were noticeable at birth but disappeared within two months, in contrast to cortical eGFP neurons that started to appear around postnatal day 3 to 5 and existed through life. Cluster eGFP neurons were not immunoreactive for SST antibodies, contrary to cortical eGFP neurons. They were also not immunolabeled by parvalbumin, a marker for another major type of interneurons, and Ca2+/calmodulin-dependent kinases II, a commonly used marker for excitatory neurons. Firing rate, afterhyperpolarization, and excitatory synaptic activity significantly enhanced in cortical eGFP neurons during postnatal development, but these properties remained mostly unchanged in cluster eGFP neurons. Short-term plasticity of the excitatory synapse showed robust facilitation in cortical eGFP neurons but depression in cluster eGFP neurons. These results implied that eGFP might also be expressed in other types of cortical neurons in addition to SST-containing interneurons in GIN mice at early postnatal ages.

Section snippets

INTRODUCTION

GABAergic interneurons are one of two major types of neurons in the neocortex, which provide inhibition for neuronal networks and play crucial roles in the brain functions (Douglas and Martin, 2004). They are remarkably heterogeneous, consisting of many subtypes with distinct molecular profiles, morphologies, and intrinsic and synaptic properties (Markram et al., 2004, Rudy et al., 2011). Most cortical interneurons are generated in the medial ganglionic eminence and the caudal ganglionic

Transgenic Mice

Homozygous transgenic mice (FVB-Tg (GadGFP) 45704Swn/J, GIN mice) were purchased from the Jackson labs (Bar Harbor, ME) and offsprings of both sexes were bred in-house and used for experiments. A total of 134 mice were used in this study. All animals were maintained on 12-h light/dark cycles and were provided food and water ad libitum. All procedures used in the study adhered to the guidelines approved by the Institutional Animal Care and Use Committee at the University of Florida and the

Two Groups of eGFP+ Neurons in the Neocortex of GIN Mice

We examined the distribution of eGFP+ neurons in the neocortex of GIN mice aged P1 to P60. In addition to eGFP+ neurons distributed in the layers II-IV and upper layer V of the neocortex (cortical eGFP neurons), we observed massive eGFP+ neurons in the deep layers of the lateral neocortex (cluster eGFP neurons, Fig. 1A, indicated by arrows). These neurons have not been studied previously. In the present work, we examined the distributions, molecular markers, intrinsic and synaptic properties of

DISCUSSION

In the present study, we observed two groups of eGFP+ neurons in the neocortex of GIN mice, cluster eGFP neurons and cortical eGFP neurons. Cortical eGFP neurons, which populate cortical layers II-IV and upper layer V and contain SST, have been extensively studied previously (Halabisky et al., 2006, Chen et al., 2009, Okaty et al., 2009, Fanselow and Connors, 2010, Kinnischtzke et al., 2012, Pan et al., 2016, Riedemann et al., 2016, Schmid et al., 2016). Cluster eGFP neurons, however, have not

Acknowledgments

We thank Drs. Liu Junhua, Su Mingzhao and Chen Dongsheng for assistance with histology and immunohistochemistry. We also thank Dr. Wang Jinhui for help in part of experiments. Funding was provided by the Southwest University of China (5330500236) to HX Chen and National Institute of Neurological Disorders and Stroke Grant NS-35651 to S. N. Roper.

References (64)

  • M Beierlein et al.

    Two dynamically distinct inhibitory networks in layer 4 of the neocortex

    J Neurophysiol

    (2003)
  • HX Chen et al.

    Long-term potentiation of excitatory synapses on neocortical somatostatin-expressing interneurons

    J Neurophysiol

    (2009)
  • A Chow et al.

    K(+) channel expression distinguishes subpopulations of parvalbumin- and somatostatin-containing neocortical interneurons

    J Neurosci

    (1999)
  • R Cossart et al.

    Dendritic but not somatic GABAergic inhibition is decreased in experimental epilepsy

    Nat Neurosci

    (2001)
  • AG Dayer et al.

    New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors

    J Cell Biol

    (2005)
  • RJ Douglas et al.

    Neuronal circuits of the neocortex

    Annu Rev Neurosci

    (2004)
  • J Du et al.

    Developmental expression and functional characterization of the potassium-channel subunit Kv3.1b in parvalbumin-containing interneurons of the rat hippocampus

    J Neurosci

    (1996)
  • DD Dunning et al.

    GABA(a) receptor-mediated miniature postsynaptic currents and alpha-subunit expression in developing cortical neurons

    J Neurophysiol

    (1999)
  • A Erisir et al.

    Function of specific K(+) channels in sustained high-frequency firing of fast-spiking neocortical interneurons

    J Neurophysiol

    (1999)
  • EE Fanselow et al.

    The roles of somatostatin-expressing (GIN) and fast-spiking inhibitory interneurons in UP-DOWN states of mouse neocortex

    J Neurophysiol

    (2010)
  • EE Fanselow et al.

    Selective, state-dependent activation of somatostatin-expressing inhibitory interneurons in mouse neocortex

    J Neurophysiol

    (2008)
  • T Fuchs et al.

    Disinhibition of somatostatin-positive GABAergic interneurons results in an anxiolytic and antidepressant-like brain state

    Mol Psychiatry

    (2017)
  • EM Goldberg et al.

    Rapid developmental maturation of neocortical FS cell intrinsic excitability

    Cereb Cortex

    (2011)
  • E Gould et al.

    Neurogenesis in the neocortex of adult primates

    Science

    (1999)
  • B Halabisky et al.

    Electrophysiological classification of somatostatin-positive interneurons in mouse sensorimotor cortex

    J Neurophysiol

    (2006)
  • S He et al.

    Early enriched environment promotes neonatal GABAergic neurotransmission and accelerates synapse maturation

    J Neurosci

    (2010)
  • D Inta et al.

    Neurogenesis and widespread forebrain migration of distinct GABAergic neurons from the postnatal subventricular zone

    Proc Natl Acad Sci U S A

    (2008)
  • AK Kinnischtzke et al.

    Postnatal maturation of somatostatin-expressing inhibitory cells in the somatosensory cortex of GIN mice

    Front Neural Circuits

    (2012)
  • Y Kubota et al.

    Dependence of GABAergic synaptic areas on the interneuron type and target size

    J Neurosci

    (2000)
  • C Le Magueresse et al.

    "small axonless neurons": postnatally generated neocortical interneurons with delayed functional maturation

    J Neurosci

    (2011)
  • CC Lien et al.

    Kv3 potassium conductance is necessary and kinetically optimized for high-frequency action potential generation in hippocampal interneurons

    J Neurosci

    (2003)
  • LC Lin et al.

    Reduced brain somatostatin in mood disorders: a common pathophysiological substrate and drug target?

    Front Pharmacol

    (2013)

    • Cited by (1)

    View full text
    © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.