Search results | In Situ Hybridization, RNA-ISH

Cerebellar granule neuron progenitors are the source of Hk2 in the postnatal cerebellum.

Cancer & Metabolism, 1(1), 15.

Gershon TR, Crowther AJ, Liu H, Miller CR, Deshmukh M (2013).
PMID: 24280296 | DOI: 24280296

Cotransmission of Acetylcholine and GABA.

Neuropharmacology. 2015 Jul 25.

Granger AJ, Mulder N, Saunders A, Sabatini BL.
PMID: 26220313 | DOI: 26220313

Neurons that produce acetylcholine (ACh) are positioned to broadly influence the brain, with axonal arborizations that extend throughout the cerebral cortex, striatum, and hippocampus. While the action of these neurons has typically been attributed entirely to ACh, neurons often release more than one primary neurotransmitter. Here, we review evidence for the cotransmission of the inhibitory neurotransmitter GABA from cholinergic neurons throughout the mammalian central nervous system. Functional cotransmission of ACh and GABA has been reported in the retina and cortex, and anatomical studies suggest that GABA cotransmission is a common feature of nearly all forebrain ACh-producing neurons. Further experiments are necessary to confirm the extent of GABA cotransmission from cholinergic neurons, and the contribution of GABA needs to be considered when studying the functional impact of activity in ACh-producing neurons.

A variant of Nesprin1 giant devoid of KASH domain underlies the molecular etiology of autosomal recessive cerebellar ataxia type I

Neurobiol Dis. 2015 Apr 2.

Razafsky D, Hodzic D.
PMID: 25843669 | DOI: 25843669

Nonsense mutations across the whole coding sequence of Syne1/Nesprin1 have been linked to autosomal recessive cerebellar ataxia Type I (ARCA1). However, nothing is known about the molecular etiology of this late-onset debilitating pathology. In this work, we report that Nesprin1 giant is specifically expressed in CNS tissues. We also identified a CNS-specific splicing event that leads to the abundant expression of a KASH-LESS variant of Nesprin1 giant (KLNes1g) in the cerebellum. KLNes1g displayed a noncanonical localization at glomeruli of cerebellar mossy fibers whereas Nesprin2 exclusively decorated the nuclear envelope of all cerebellar neurons. In immunogold electron microscopy, KLNes1g colocalized both with synaptic vesicles within mossy fibers and with dendritic membranes of cerebellar granule neurons. We further identified vesicle- and membrane-associated proteins in KLNes1g immunoprecipitates. Together, our results suggest that the loss of function of KLNes1g resulting from Nesprin1 nonsense mutations underlies the molecular etiology of ARCA1.

GABAergic Projections from Lateral Hypothalamus to Paraventricular Hypothalamic Nucleus Promote Feeding

J Neurosci. 2015 Feb 25;35(8):3312-8.

Wu Z, Kim ER, Sun H, Xu Y, Mangieri LR, Li DP, Pan HL, Xu Y, Arenkiel BR, Tong Q.
PMID: 25716832 | DOI: 25716832

Lesions of the lateral hypothalamus (LH) cause hypophagia. However, activation of glutamatergic neurons in LH inhibits feeding. These results suggest a potential importance for other LH neurons in stimulating feeding. Our current study in mice showed that disruption of GABA release from adult LH GABAergic neurons reduced feeding. LH GABAergic neurons project extensively to the paraventricular hypothalamic nucleus (PVH), and optogenetic stimulation of GABAergic LH → PVH fibers induced monosynaptic IPSCs in PVH neurons, and potently increased feeding, which depended on GABA release. In addition, disruption of GABA-A receptors in the PVH reduced feeding. Thus, we have identified a new feeding pathway in which GABAergic projections from the LH to the PVH promote feeding.

Expression of Hedgehog ligand and signal transduction components in mutually distinct isocitrate dehydrogenase mutant glioma cells supports a role for paracrine signaling

J Neurooncol. 2014 May 28.

Abiria SA, Williams TV, Munden AL, Grover VK, Wallace A, Lundberg CJ, Valadez JG, Cooper MK.
PMID: 24867209 | DOI: 24867209

Hedgehog (Hh) signaling regulates the growth of malignant gliomas by a ligand-dependent mechanism. The cellular source of Sonic Hh ligand and mode of signaling have not been clearly defined due to the lack of methods to definitively identify neoplastic cells in glioma specimens. Using an antibody specific for mutant isocitrate dehydrogenase protein expression to identify glioma cells, we demonstrate that Sonic Hh ligand and the pathway components Patched1 (PTCH1) and GLI1 are expressed in neoplastic cells. Further, Sonic Hh ligand and its transcriptional targets, PTCH1 and GLI1, are expressed in mutually distinct populations of neoplastic cells. These findings support a paracrine mode of intratumoral Hh signaling in malignant gliomas.

Social and novel contexts modify hippocampal CA2 representations of space.

Nat Commun.

2016 Jan 25

Alexander GM, Farris S, Pirone JR, Zheng C, Colgin LL, Dudek SM.
PMID: 26806606 | DOI: 26806606

The hippocampus supports a cognitive map of space and is critical for encoding declarative memory (who, what, when and where). Recent studies have implicated hippocampal subfield CA2 in social and contextual memory but how it does so remains unknown. Here we find that in adult male rats, presentation of a social stimulus (novel or familiar rat) or a novel object induces global remapping of place fields in CA2 with no effect on neuronal firing rate or immediate early gene expression. This remapping did not occur in CA1, suggesting this effect is specific for CA2. Thus, modification of existing spatial representations might be a potential mechanism by which CA2 encodes social and novel contextual information.

The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3.

Genes Dev.

2016 Jun 15

Vidal V, Sacco S, Rocha AS, da Silva F, Panzolini C, Dumontet T, Doan TM, Shan J, Rak-Raszewska A, Bird T, Vainio S, Martinez A, Schedl A
PMID: 27313319 | DOI: 27313319

Adrenal glands are zonated endocrine organs that are essential in controlling body homeostasis. How zonation is induced and maintained and how renewal of the adrenal cortex is ensured remain a mystery. Here we show that capsular RSPO3 signals to the underlying steroidogenic compartment to induce β-catenin signaling and imprint glomerulosa cell fate. Deletion of RSPO3 leads to loss of SHH signaling and impaired organ growth. Importantly, Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa. Thus, the adrenal capsule acts as a central signaling center that ensures replacement of damaged cells and is required to maintain zonation throughout life.

Antagonistic negative and positive neurons of the basolateral amygdala.

Nat Neurosci.

2016 Oct 17

Kim J, Pignatelli M, Xu S, Itohara S, Tonegawa S.
PMID: 27749826 | DOI: 27749826

The basolateral amygdala (BLA) is a site of convergence of negative and positive stimuli and is critical for emotional behaviors and associations. However, the neural substrate for negative and positive behaviors and relationship between negative and positive representations in the basolateral amygdala are unknown. Here we identify two genetically distinct, spatially segregated populations of excitatory neurons in the mouse BLA that participate in valence-specific behaviors and are connected through mutual inhibition. These results identify a genetically defined neural circuit for the antagonistic control of emotional behaviors and memories.

Distinct Corticostriatal GABAergic Neurons Modulate Striatal Output Neurons and Motor Activity.

Cell Rep.

2017 May 02

Melzer S, Gil M, Koser DE, Michael M, Huang KW, Monyer H.
PMID: 28467898 | DOI: 28467898

The motor cortico-basal ganglion loop is critical for motor planning, execution, and learning. Balanced excitation and inhibition in this loop is crucial for proper motor output. Excitatory neurons have been thought to be the only source of motor cortical input to the striatum. Here, we identify long-range projecting GABAergic neurons in the primary (M1) and secondary (M2) motor cortex that target the dorsal striatum. This population of projecting GABAergic neurons comprises both somatostatin-positive (SOM+) and parvalbumin-positive (PV+) neurons that target direct and indirect pathway striatal output neurons as well as cholinergic interneurons differentially. Notably, optogenetic stimulation of M1 PV+ and M2 SOM+ projecting neurons reduced locomotion, whereas stimulation of M1 SOM+ projecting neurons enhanced locomotion. Thus, corticostriatal GABAergic projections modulate striatal output and motor activity.

Development of a head-mounted wireless microstimulator for deep brain stimulation in rats.

J Neurosci Methods.

2017 Aug 22

Fluri F, Mützel T, Schuhmanna MK, Krstić M, Endres H, Volkmann J.
PMID: 28842194 | DOI: 28842194

Abstract

BACKGROUND:

Commercial neurostimulators for clinical use are effective in patients; however they are too large and prohibitively expensive for preclinical studies. Thus, there is an urgent need of a small inexpensive and wireless microstimulator which is fully programmable in frequency, pulse width and amplitude for rodent experiments.

NEW METHODS:

Rats were subjected to a photothrombotic stroke of the right sensorimotor cortex and a microelectrode was implanted in the right mesencephalic locomotor region. The microstimulator was connected with the head plug of the rat. Three different stimulation frequencies were applied and different stimulating amplitudes were chosen. Under these conditions, gait velocity and locomotor behavior of six rats were examined on a beam.

RESULTS:

The head-mounted microstimulator allowed freedom in all motor activities performed spontaneously by the tested rats. Increasing either the frequency or the stimulating amplitude increased gait velocity and ameliorated locomotor behavior after stroke.

COMPARISON WITH EXISTING METHODS:

Other devices for DBS in rodents must be implanted under the skin or worn in an animal jacket on the back by the tested rat. Some available systems require even a tethering of the tested animal via a cable to an external stimulation system, which limits the freedom of movement.

CONCLUSION:

Here, we present a freely programmable microstimulator including DBS-typical stimulating parameters. The lightweight device is connected by a simple plug to the head allowing full freedom of movement and exchange of batteries for long-term experiments. The design of this stimulator is suitable for sophisticated behavior tests requiring balance and skilled walking.

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Advanced Cell Diagnostics China

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Advanced Cell Diagnostics

Advanced Cell Diagnostics , S.r.l.

Advanced Cell Diagnostics China

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