Neuropeptide Y conjugated to saporin alters anxiety-like behavior when injected into the central nucleus of the amygdala or basomedial hypothalamus in BALB/cJ mice

Lyons, Angela M.; Thiele, Todd E.

doi:10.1016/j.peptides.2010.09.009

Cited by 18 publications

(13 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These data are consistent with reports implicating CeA involvement in anxiety 9,11,12 , but it is important to note that our findings do not exclude downstream or parallel circuits including the BNST 28 , the insular and prefrontal cortices 29 , and the septal-hippocampal circuit 30 ; for example, stress induces CeL release of corticotropin releasing hormone (CRH) in the BNST 28 . In the course of providing insight into native anxiogenic and anxiolytic processes, these findings demonstrate that anxiety is continuously regulated by balanced antagonistic pathways within the amygdala, and illustrate the importance of resolving specific projections in the study of neural circuit function relevant to psychiatric disease.…”

supporting

confidence: 90%

Amygdala circuitry mediating reversible and bidirectional control of anxiety

Tye

Prakash

Kim

et al. 2011

Nature

1,095

963

View full text Add to dashboard Cite

Anxiety, a sustained state of heightened apprehension in the absence of immediate threat, becomes severely debilitating in disease states1. Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence)2, and contribute to the etiology of major depression and substance abuse3,4. Although it has been proposed that the amygdala, a brain region important for emotional processing5–8, has a role in anxiety9–13, neural mechanisms that control anxiety remain unclear. Here we explore neural circuits underlying anxiety-related behaviors by using optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of optogenetics14–16 to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA-achieved by viral transduction of the BLA with a codon-optimized channelrhodopsin followed by restricted illumination in downstream CeA - exerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin15 (eNpHR3.0) increased anxiety-related behaviors. Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific BLA-CeA projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease.

show abstract

supporting

confidence: 90%

Amygdala circuitry mediating reversible and bidirectional control of anxiety

Tye

Prakash

Kim

et al. 2011

Nature

1,095

963

View full text Add to dashboard Cite

show abstract

“…The whole brain was sliced into 40 mm sections using a Leica VT 1000S vibratome (Leica Microsystems, Nussloch, Germany) and stored in a cryopreserve solution until IR analysis. The sections were cut into three sets and processed with antibodies raised against NPY (Phoenix Pharmaceuticals; 1 : 1000; Thiele et al, 2000), Y1R (Antibody 96106 raised against NPY Y1R was provided by CURE/Digestive Disease Research Center, Antibody/RIA Core, NIH grant DK41301 (Los Angeles, CA); 1 : 25 000; Lyons and Thiele, 2010), or Y2R (Neuromics, Edina, MN; 1 : 4000). Tissues from all experimental groups were run through each assay at the same time for each antibody tested.…”

Section: Effects Of Binge-like Ethanol Drinking On Npy Y1r and Y2r Irmentioning

confidence: 99%

“…Specificity of the NPY antibody was verified with colocalization of green fluorescent protein (GFP) and NPY (495%) in NPY-sappphire-GFP transgenic mice (Pinto et al, 2004). NPY and Y1R IR were visualized using standard 3,3 0 -diamino-benzidine (DAB) procedures that we have described previously (Hayes et al, 2005;Lyons and Thiele, 2010;Navarro et al, 2008). Because Y2R IR is less easily detected, sections for Y2R IR underwent an amplification procedure using a Tyramide Signal Amplification (TSA) detection kit (Jackson Laboratories) to increase signal sensitivity.…”

Section: Effects Of Binge-like Ethanol Drinking On Npy Y1r and Y2r Irmentioning

confidence: 99%

Central Neuropeptide Y Modulates Binge-Like Ethanol Drinking in C57BL/6J Mice via Y1 and Y2 Receptors

Sparrow

Lowery-Gionta

Pleil

et al. 2012

Neuropsychopharmacol

View full text Add to dashboard Cite

Frequent binge drinking has been linked to heart disease, high blood pressure, type 2 diabetes, and the development of ethanol dependence. Thus, identifying pharmaceutical targets to treat binge drinking is of paramount importance. Here we employed a mouse model of binge-like ethanol drinking to study the role of neuropeptide Y (NPY). To this end, the present set of studies utilized pharmacological manipulation of NPY signaling, immunoreactivity (IR) mapping of NPY and NPY receptors, and electrophysiological recordings from slice preparations of the amygdala. The results indicated that central infusion of NPY, a NPY Y1 receptor (Y1R) agonist, and a Y2R antagonist significantly blunted binge-like ethanol drinking in C57BL/6J mice (that achieved blood ethanol levels >80 mg/dl in control conditions). Binge-like ethanol drinking reduced NPY and Y1R IR in the central nucleus of the amygdala (CeA), and 24 h of ethanol abstinence after a history of binge-like drinking promoted increases of Y1R and Y2R IR. Electrophysiological recordings of slice preparations from the CeA showed that binge-like ethanol drinking augmented the ability of NPY to inhibit GABAergic transmission. Thus, binge-like ethanol drinking in C57BL/6J mice promoted alterations of NPY signaling in the CeA, and administration of exogenous NPY compounds protected against binge-like drinking. The current data suggest that Y1R agonists and Y2R antagonists may be useful for curbing and/or preventing binge drinking, protecting vulnerable individuals from progressing to the point of ethanol dependence.

show abstract

“…The neuropeptides play diverse and critical roles in regulating neuronal structures and functions in the central nervous system (Brain and Cox ; Sharf et al . ; Lyons and Thiele ). However, the role of neuropeptides in synaptic plasticity is less well known than that of classical neuronal transmitters, such as glutamate and γ‐aminobutyric acid (GABA).…”

mentioning

confidence: 98%

Calcitonin gene‐related peptide erases the fear memory and facilitates long‐term potentiation in the central nucleus of the amygdala in rats

Zhang

Liu

et al. 2015

Journal of Neurochemistry

View full text Add to dashboard Cite

Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide, which plays a critical role in the central nervous system. CGRP binds to G protein-coupled receptors, including CGRP1, which couples positively to adenylyl cyclase (AC) and protein kinase A (PKA) activation. CGRP and CGRP1 receptors are enriched in central nucleus of the amygdala (CeA), the main part of the amygdala, which regulates conditioned fear memories. Here, we reported the importance of CGRP and CGRP1 receptor for synaptic plasticity in the CeA and the extinction of fear memory in rats. Our electrophysiological and behavioral in vitro and in vivo results showed exogenous application of CGRP induced an immediate and lasting longterm potentiation in the basolateral nucleus of amygdala-CeA pathway, but not in the lateral nucleus of amygdala-CeA pathway, while bilateral intra-CeA infusion CGRP (0, 5, 13 and 21 lM/side) dose dependently enhanced fear memory extinction. The effects were blocked by CGRP1 receptor antagonist ), N-methyl-D-aspartate receptors antagonist MK801 and PKA inhibitor H89. These results demonstrate that CGRP can lead to long-term potentiation of basolateral nucleus of amygdala-CeA pathway through a PKA-dependent postsynaptic mechanism that involved N-methyl-D-aspartate receptors and enhance the extinction of fear memory in rats. Together, the results strongly support a pivotal role of CGRP in the synaptic plasticity of CeA and extinction of fear memory. Keywords: calcitonin gene-related peptide, central nucleus of amygdala, fear extinction, long-term potentiation, synaptic plasticity. The neuropeptides play diverse and critical roles in regulating neuronal structures and functions in the central nervous system (Brain and Cox 2006;Sharf et al. 2008;Lyons and Thiele 2010). However, the role of neuropeptides in synaptic plasticity is less well known than that of classical neuronal transmitters, such as glutamate and c-aminobutyric acid (GABA). Calcitonin gene-related peptide (CGRP) is produced by calcitonin gene and expressed throughout the central and peripheral nervous system, especially in the nucleus accumbens, the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST), Received February 10, 2015; revised manuscript received May 10, 2015; accepted July 1, 2015. Address correspondence and reprint requests to Dr Fang Wang, Department of Pharmacology, School of Basic Medicine, Tongji Medical College, HUST, Number 13, Hangkong Road, Wuhan, Hubei 430030, China. E-mail: wangfangtj0322@163.com Abbreviations used: ACSF, artificial cerebrospinal fluid; AMPA, alphaamino-3-hydroxy-5-methylisoxazole-4-propionate; BLA, basolateral nucleus of amygdala; BNST, bed nucleus of the stria terminalis; CeA, central nucleus of the amygdala; CGRP, calcitonin gene-related peptide; CS, conditioned stimulus; fEPSP, field excitatory postsynaptic potential; LA, lateral nucleus of amygdala; LTP, long-term potentiation; NAc, nucleus accumbens; PFC, prefrontal cortex; US, unconditioned stimulus.

show abstract

Neuropeptide Y conjugated to saporin alters anxiety-like behavior when injected into the central nucleus of the amygdala or basomedial hypothalamus in BALB/cJ mice

Cited by 18 publications

References 30 publications

Amygdala circuitry mediating reversible and bidirectional control of anxiety

Amygdala circuitry mediating reversible and bidirectional control of anxiety

Central Neuropeptide Y Modulates Binge-Like Ethanol Drinking in C57BL/6J Mice via Y1 and Y2 Receptors

Calcitonin gene‐related peptide erases the fear memory and facilitates long‐term potentiation in the central nucleus of the amygdala in rats

Contact Info

Product

Resources

About