Smad3 deficiency inhibits dentate gyrus LTP by enhancing GABAA neurotransmission

Mª Dolores Muñoz; Mónica Antolín‐Vallespín; Silvia Tapia‐González; Amelia Sánchez‐Capelo

doi:10.1111/jnc.13558

journal article Feb 18, 2016

Smad3 deficiency inhibits dentate gyrus LTP by enhancing GABAA neurotransmission

Mª Dolores Muñoz Mónica Antolín‐Vallespín Silvia Tapia‐González Amelia Sánchez‐Capelo

Journal of Neurochemistry Vol. 137 No. 2 pp. 190-199 · Wiley

View at Publisher Save 10.1111/jnc.13558

Abstract

AbstractTransforming growth factor‐β signaling through intracellular Smad3 has been implicated in Parkinson's disease (PD) and it fulfills an important role in the neurogenesis and synaptic plasticity that occurs in the adult dentate gyrus (DG). The long‐term potentiation (LTP) induced in the DG by high‐frequency stimulation of the medial perforant pathway is abolished in the DG of Smad3‐deficient mice, but not in the CA1 hippocampal region. Here, we show that NMDA‐ and AMPA‐type glutamate receptors do not participate in the inhibition of LTP associated with Smad3 deficiency. Moreover, there is no difference in the hippocampal GAD65 and GAD67 content, suggesting that GABA biosynthesis remains unaffected. Increased conductance and higher action potential firing thresholds were evident in intracellular recordings of granule cells from Smad3 deficient mice. Interestingly, phasic and tonic GABAA receptor (GABAAR)‐mediated neurotransmission is enhanced in the DG of Smad3‐deficient mice, and LTP induction can be rescued by inhibiting GABAAR with picrotoxin. Hence, Smad3 signaling in the DG appears to be necessary to induce LTP by regulating GABAA neurotransmission, suggesting a central role of this intracellular signaling pathway in the hippocampal brain plasticity related to learning and memory.
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Smad3 deficient mice represent a new and interesting model of Parkinson's disease, displaying hippocampal dysfunctions that include decreased neurogenesis and the failure to induce LTP in the dentate gyrus. Here we show that Smad3 deficiency inhibits LTP induction by enhancing phasic and tonic GABAA receptor‐mediated neurotransmission, while LTP induction can be rescued with a GABAA receptor antagonist. Alteration of GABA neurotransmission is thought to produce hippocampal cognitive dysfunction in Down's syndrome or Alzheimer's disease, and here we provide new insights into the hippocampal changes in an animal model of Parkinson's disease.

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References

60

[1]

10.1016/s0165-0270(01)00374-0

[2]

The mechanisms of the strong inhibitory modulation of long-term potentiation in the rat dentate gyrus

Fumiko Arima-Yoshida, Ayako M. Watabe, Toshiya Manabe

European Journal of Neuroscience 10.1111/j.1460-9568.2011.07657.x

[3]

10.1016/j.neuroscience.2009.06.045

[4]

10.1016/j.biopsych.2013.02.015

[5]

10.1016/j.neuron.2011.12.012

[6]

10.1113/jphysiol.1996.sp021806

[7]

10.1038/35051086

[8]

10.1038/sj.bjp.0704795

[9]

10.1016/s1474-4422(13)70118-2

[10]

10.1523/jneurosci.3393-11.2012

[11]

10.1152/jn.1993.69.4.1150

[12]

10.1016/s0079-6123(07)63014-3

[13]

10.1016/j.cell.2008.09.060

[14]

10.1523/jneurosci.0234-12.2012

[15]

10.1038/nrn1625

[16]

10.1016/s0165-3806(01)00288-7

[17]

10.1186/s40478-014-0176-9

[18]

10.1016/j.neuron.2007.11.002

[19]

10.1523/jneurosci.4141-11.2012

[20]

10.1111/j.1460-9568.2010.07331.x

[21]

10.1016/j.neuroscience.2013.01.008

[22]

10.1152/jn.00240.2003

[23]

10.1002/ana.410200106

[24]

10.3389/fnagi.2013.00043

[25]

10.1002/jnr.21072

[26]

10.1074/jbc.r115.652750

[27]

10.1523/jneurosci.1203-12.2013

[28]

10.1016/0304-3940(95)11686-q

[29]

Mott D. D. "GABAB autoreceptors mediate activity‐dependent disinhibition and enhance signal transmission in the dentate gyrus" J. Neurophysiol. (1993) 10.1152/jn.1993.69.3.674

[30]

10.1038/npp.2014.43

[31]

10.1016/0165-0270(81)90049-2

[32]

10.1152/jn.2002.87.5.2624

[33]

Differential Expression of TGF-β1, 2 and 3 Isotypes in Alzheimerʼs Disease: A Comparative Immunohistochemical Study with Cerebral Infarction, Aged Human and Mouse Control Brains

Nancy S. Peress, Edward Perillo

Journal of Neuropathology and Experimental Neurolo... 10.1097/00005072-199511000-00007

[34]

10.3389/fnsyn.2012.00005

[35]

10.1007/s10072-006-0562-6

[36]

10.1016/j.cytogfr.2004.11.002

[37]

10.1016/s1044-7431(03)00081-2

[38]

10.1016/s0896-6273(04)00152-7

[39]

10.1177/1073858411435129

[40]

10.1523/jneurosci.5702-11.2012

[41]

10.1523/jneurosci.14-09-05325.1994

[42]

10.1113/jphysiol.1995.sp020973

[43]

10.1523/jneurosci.0789-10.2010

[44]

10.1523/jneurosci.4829-12.2013

[45]

10.1186/1750-1326-6-72

[46]

10.1186/1478-811x-11-93

[47]

Increased intrathecal levels of the angiogenic factors VEGF and TGF-β in Alzheimer’s disease and vascular dementia

Elisabeth Tarkowski, Razao Issa, Magnus Sjögren et al.

Neurobiology of Aging 10.1016/s0197-4580(01)00285-8

[48]

10.1111/j.1460-9568.2005.04189.x

[49]

10.1111/j.1460-9568.2006.05109.x

[50]

10.1006/exnr.1996.0200

Showing 50 of 60 references

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Details

Published: Feb 18, 2016
Vol/Issue: 137(2)
Pages: 190-199
License: View

Authors

M

Mª Dolores Muñoz

Unidad de Neurología Experimental Hospital Universitario Ramón y Cajal – IRYCIS Madrid Spain

M

Mónica Antolín‐Vallespín

CIBERNED ‐ Ser. Neurobiología – Investigación Hospital Universitario Ramón y Cajal – IRYCIS Madrid Spain

S

Silvia Tapia‐González

CIBERNED ‐ Ser. Neurobiología – Investigación Hospital Universitario Ramón y Cajal – IRYCIS Madrid Spain

A

Amelia Sánchez‐Capelo

CIBERNED ‐ Ser. Neurobiología – Investigación Hospital Universitario Ramón y Cajal – IRYCIS Madrid Spain

Funding

Instituto de Salud Carlos III Award: PI12/00258

Cite This Article

Mª Dolores Muñoz, Mónica Antolín‐Vallespín, Silvia Tapia‐González, et al. (2016). Smad3 deficiency inhibits dentate gyrus LTP by enhancing GABAA neurotransmission. Journal of Neurochemistry, 137(2), 190-199. https://doi.org/10.1111/jnc.13558

Smad3 deficiency inhibits dentate gyrus LTP by enhancing GABAA neurotransmission

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