Differential Distribution of Four Hyperpolarization-Activated Cation Channels in Mouse Brain

1999 ◽  
Vol 380 (7-8) ◽  
pp. 975-980 ◽  
Author(s):  
S. Moosmang ◽  
M. Biel ◽  
F. Hofmann ◽  
A. Ludwig
Keyword(s):  
Olfactory Bulb ◽  
Mouse Brain ◽  
Cellular Localization ◽  
Pyramidal Neurons ◽  
Cation Channels ◽  
Hcn Channel ◽  
Differential Distribution ◽  
Hippocampal Pyramidal Neurons ◽  
Low Levels ◽  
The Brain

Abstract Hyperpolarization-activated cation currents, termed Ih, are observed in a variety of neurons. Four members of a gene family encoding hyperpolarization-activated cyclic-nucleotide-gated cation channels (HCN1-4) have been cloned. The regional expression and cellular localization of the four HCN channel types in mouse brain was investigated using in situ hybridization. The expression of HCN1 was restricted to the olfactory bulb, cerebral cortex, hippocampus, superior colliculus and cerebellum. In contrast, HCN2 transcripts were found at high levels nearly ubiquitiously in the brain, and the strongest signals were seen in the olfactory bulb, hippocampus, thalamus and brain stem. HCN3 was uniformly expressed at very low levels throughout the brain. Finally, HCN4 transcripts were prominently expressed selectively in the thalamus and olfactory bulb. Some neurons expressed two or more HCN channel transcripts including hippocampal pyramidal neurons (HCN1, HCN2 and low levels of HCN 4) and thalamic relay neurons (HCN2 and HCN4). Our results demonstrate that each HCN channel transcript has a unique distribution in the brain. Furthermore, they suggest that the heterogeneity of neuronal Ih may be, at least in part, due to the differential expression of HCN channel genes.

scholarly journals Gating transitions and modulation of a hetero-octameric AMPA glutamate receptor

2020 ◽  
Author(s):  
Ingo Greger ◽  
Danyang Zhang ◽  
Jake Watson ◽  
Peter Matthews ◽  
Ondrej Cais
Keyword(s):  
Pyramidal Neurons ◽  
Specific Lipids ◽  
Conduction Path ◽  
Hippocampal Pyramidal Neurons ◽  
Binding Domains ◽  
Excitatory Transmission ◽  
Auxiliary Subunit ◽  
Cryo Electron Microscopy ◽  
Er Export ◽  
The Brain

Abstract AMPA glutamate receptors (AMPARs) mediate the majority of excitatory transmission in the brain, and enable synaptic plasticity that underlies learning 1. A diverse array of AMPAR signaling complexes are established by receptor auxiliary subunits, associating in various combinations to modulate trafficking, gating and synaptic strength 2. However, their mechanisms of action are poorly understood. Here, we determine cryo-electron microscopy structures of the heteromeric GluA1/2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states (at 3.2 and 3.7 Å, respectively). Consequential for gating regulation, two γ8 and two CNIH2 subunits lodge at distinct sites beneath the ligand-binding domains of the receptor tetramer, with site-specific lipids shaping each interaction. Activation leads to a stark asymmetry between GluA1 and GluA2 along the ion conduction path, and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, that promotes the active-state conformation. In addition, both γ8 and CNIH2 pivot towards the pore exit on activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this ER-export factor into a powerful positive AMPAR modulator, capable of providing hippocampal pyramidal neurons with their integrative synaptic properties.

scholarly journals Three-dimensional, isotropic imaging of mouse brain using multi-view deconvolution light sheet microscopy

2017 ◽  
Vol 10 (05) ◽  
pp. 1743006 ◽  
Author(s):  
Sa Liu ◽  
Jun Nie ◽  
Yusha Li ◽  
Tingting Yu ◽  
Dan Zhu ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Pyramidal Neurons ◽  
Structural Information ◽  
Fluorescent Microscopy ◽  
Three Dimensional ◽  
Light Sheet ◽  
Nerve Fibers ◽  
Single View ◽  
Light Sheet Microscopy ◽  
The Brain

We present a three-dimensional (3D) isotropic imaging of mouse brain using light-sheet fluorescent microscopy (LSFM) in conjunction with a multi-view imaging computation. Unlike common single view LSFM is used for mouse brain imaging, the brain tissue is 3D imaged under eight views in our study, by a home-built selective plane illumination microscopy (SPIM). An output image containing complete structural information as well as significantly improved resolution ([Formula: see text]4 times) are then computed based on these eight views of data, using a bead-guided multi-view registration and deconvolution. With superior imaging quality, the astrocyte and pyramidal neurons together with their subcellular nerve fibers can be clearly visualized and segmented. With further including other computational methods, this study can be potentially scaled up to map the connectome of whole mouse brain with a simple light-sheet microscope.

scholarly journals Rapid Loss of Dendritic HCN Channel Expression in Hippocampal Pyramidal Neurons following Status Epilepticus

2011 ◽  
Vol 31 (40) ◽  
pp. 14291-14295 ◽  
Author(s):  
S. Jung ◽  
L. N. Warner ◽  
J. Pitsch ◽  
A. J. Becker ◽  
N. P. Poolos
Keyword(s):  
Status Epilepticus ◽  
Pyramidal Neurons ◽  
Hcn Channel ◽  
Rapid Loss ◽  
Hippocampal Pyramidal Neurons ◽  
Channel Expression

scholarly journals Apolipoprotein D is Elevated in Oligodendrocytes in the Peri-Infarct Region after Experimental Stroke: Influence of Enriched Environment

2007 ◽  
Vol 28 (3) ◽  
pp. 551-562 ◽  
Author(s):  
Mattias Rickhag ◽  
Tomas Deierborg ◽  
Shutish Patel ◽  
Karsten Ruscher ◽  
Tadeusz Wieloch
Keyword(s):  
Cellular Localization ◽  
Pyramidal Neurons ◽  
Recovery Period ◽  
Enriched Environment ◽  
Experimental Stroke ◽  
Regenerative Processes ◽  
Lipid Trafficking ◽  
Injured Brain ◽  
Apolipoprotein D ◽  
The Brain

Injury to the brain (e.g., stroke) results in a disruption of neuronal connectivity and loss of fundamental sensori-motor functions. The subsequent recovery of certain functions involves structural rearrangements in areas adjacent to the infarct. This remodeling of the injured brain requires trafficking of macromolecular components including cholesterol and phospholipids, a transport carried out by apolipoproteins including apolipoprotein D (apoD). We investigated the changes in the levels of apoD mRNA and protein, and its cellular localization during a recovery period up to 30 days after experimental stroke in the rat brain. In the core of the brain infarct, apoD immunoreactivity but not mRNA increased in dying pyramidal neurons, indicative of cellular redistribution of lipids. During 2 to 7 days of recovery after stroke, the apoD levels increased in the peri-infarct and white matter areas in cells identified as mature oligodendrocytes. The apoD expressing cells were conspicuously located along the rim of the infarct, suggesting a role for apoD in tissue repair. Furthermore, housing animals in an enriched environment improved sensori-motor function and increased the apoD levels. Our data strongly suggest that apoD is involved in regenerative processes and scar formation in the peri-infarct area presumably by enhancing lipid trafficking.

scholarly journals Gating transitions and modulation of a hetero-octameric AMPA glutamate receptor

2020 ◽  
Author(s):  
Danyang Zhang ◽  
Jake F Watson ◽  
Peter M Matthews ◽  
Ondrej Cais ◽  
Ingo H Greger
Keyword(s):  
Pyramidal Neurons ◽  
Specific Lipids ◽  
Conduction Path ◽  
Hippocampal Pyramidal Neurons ◽  
Binding Domains ◽  
Excitatory Transmission ◽  
Auxiliary Subunit ◽  
Cryo Electron Microscopy ◽  
Er Export ◽  
The Brain

AMPA glutamate receptors (AMPARs) mediate the majority of excitatory transmission in the brain, and enable synaptic plasticity that underlies learning 1. A diverse array of AMPAR signaling complexes are established by receptor auxiliary subunits, associating in various combinations to modulate trafficking, gating and synaptic strength 2. However, their mechanisms of action are poorly understood. Here, we determine cryo-electron microscopy structures of the heteromeric GluA1/2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states (at 3.2 and 3.7 Å, respectively). Consequential for gating regulation, two γ8 and two CNIH2 subunits lodge at distinct sites beneath the ligand-binding domains of the receptor tetramer, with site-specific lipids shaping each interaction. Activation leads to a stark asymmetry between GluA1 and GluA2 along the ion conduction path, and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, that promotes the active-state conformation. In addition, both γ8 and CNIH2 pivot towards the pore exit on activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this ER-export factor into a powerful positive AMPAR modulator, capable of providing hippocampal pyramidal neurons with their integrative synaptic properties.

scholarly journals Immunolocalization of Estrogen Receptor β in the Mouse Brain: Comparison with Estrogen Receptor α

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 2055-2067 ◽  
Author(s):  
Sudha Warrier Mitra ◽  
Elena Hoskin ◽  
Joel Yudkovitz ◽  
Lisset Pear ◽  
Hilary A. Wilkinson ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cerebral Cortex ◽  
Olfactory Bulb ◽  
Mouse Brain ◽  
Preoptic Area ◽  
Estrogen Receptor Α ◽  
Hypothalamic Nucleus ◽  
Similar Distribution ◽  
Dependent Manner ◽  
The Brain

Estrogen receptor α (ERα) and ERβ are members of the steroid nuclear receptor family that modulate gene transcription in an estrogen-dependent manner. ER mRNA and protein have been detected both peripherally and in the central nervous system, with most data having come from the rat. Here we report the development of an ERβ-selective antibody that cross-reacts with mouse, rat, and human ERβ protein and its use to determine the distribution of ERβ in the murine brain. Further, a previously characterized polyclonal antibody to ERα was used to compare the distribution of the two receptors in the first comprehensive description of ER distribution specifically in the mouse brain. ERβ immunoreactivity (ir) was primarily localized to cell nuclei within select regions of the brain, including the olfactory bulb, cerebral cortex, septum, preoptic area, bed nucleus of the stria terminalis, amygdala, paraventricular hypothalamic nucleus, thalamus, ventral tegmental area, substantia nigra, dorsal raphe, locus coeruleus, and cerebellum. Extranuclear-ir was detected in several areas, including fibers of the olfactory bulb, CA3 stratum lucidum, and CA1 stratum radiatum of the hippocampus and cerebellum. Although both receptors were generally expressed in a similar distribution through the brain, nuclear ERα-ir was the predominant subtype in the hippocampus, preoptic area, and most of the hypothalamus, whereas it was sparse or absent from the cerebral cortex and cerebellum. Collectively, these findings demonstrate the region-selective expression of ERβ and ERα in the adult ovariectomized mouse brain. These data provide an anatomical framework for understanding the mechanisms by which estrogen regulates specific neural systems in the mouse.

ADRENOCORTICAL FUNCTION IN PATIENTS WITH ACUTE SEVERE BRAIN AND PITUITARY LESION

1962 ◽  
Vol 40 (2) ◽  
pp. 254-262 ◽  
Author(s):  
H. H. Bassøe ◽  
R. Emberland ◽  
E. Glück ◽  
K. F. Støa
Keyword(s):  
Pituitary Gland ◽  
Adrenal Cortex ◽  
Artificial Ventilation ◽  
Practical Significance ◽  
Adrenocortical Function ◽  
The Third ◽  
Low Levels ◽  
Pituitary Lesion ◽  
Steroid Excretion ◽  
The Brain

ABSTRACT The steroid excretion and the plasma corticosteroids were investigated in three patients with necrosis of the brain and of the pituitary gland. The patients were kept alive by artificial ventilation. In two of the patients the neutral 17-ketosteroids and the 17-hydrocorticosteroids fell to extremely low levels. At the same time, the number of eosinophil cells showed a tendency to increase. Corticotrophin administered intravenously twice to the third patient had a stimulating effect on the adrenal cortex. The theoretical and practical significance of these findings is discussed.

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