RGD Reference Report - Neurotrophins regulate cholinergic synaptic transmission in cultured rat sympathetic neurons through a p75-dependent mechanism. - Rat Genome Database

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Neurotrophins regulate cholinergic synaptic transmission in cultured rat sympathetic neurons through a p75-dependent mechanism.

Authors: Luther, JA  Enes, J  Birren, SJ 
Citation: Luther JA, etal., J Neurophysiol. 2013 Jan;109(2):485-96. doi: 10.1152/jn.00076.2011. Epub 2012 Oct 31.
RGD ID: 10414080
Pubmed: PMID:23114219   (View Abstract at PubMed)
PMCID: PMC3545462   (View Article at PubMed Central)
DOI: DOI:10.1152/jn.00076.2011   (Journal Full-text)

The sympathetic nervous system regulates many essential physiological systems, and its dysfunction is implicated in cardiovascular diseases. Mechanisms that control the strength of sympathetic output are therefore potential targets for the management of these disorders. Here we show that neurotrophins rapidly potentiate cholinergic transmission between cultured rat sympathetic neurons. We found that brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), acting at the p75 receptor, increased the amplitude of excitatory postsynaptic currents (EPSCs). We observed increased amplitude but not frequency of miniature synaptic currents after p75 activation, suggesting that p75 acts postsynaptically to modulate transmission at these synapses. This neurotrophic modulation enhances cholinergic EPSCs via sphingolipid signaling. Application of sphingolactone-24, an inhibitor of neutral sphingomyelinase, blocked the effect of BDNF, implicating a sphingolipid pathway. Furthermore, application of the p75-associated sphingolipid second messengers C(2)-ceramide and d-erythro-sphingosine restricted to the postsynaptic cell mimicked BDNF application. Postsynaptic blockade of ceramide production with fumonisin, a ceramide synthase inhibitor, blocked the effects of BDNF and d-erythro-sphingosine, implicating ceramide or ceramide phosphate as the active signal. Together these data suggest that neurotrophin signaling, which occurs in vivo via release from sympathetic neurons and target tissues such as the heart, acutely regulates the strength of the sympathetic postganglionic response to central cholinergic inputs. This pathway provides a potential mechanism for modulating the strength of sympathetic drive to target organs such as the heart and could play a role in the development of cardiovascular diseases.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of excitatory postsynaptic potential  IMP 10414080 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ngfr  (nerve growth factor receptor)


Additional Information