Presynaptic NMDA receptors mediate IPSC potentiation at GABAergic synapses in developing rat neocortex.

<h4>Background</h4>NMDA receptors are traditionally viewed as being located postsynaptically, at both synaptic and extrasynaptic locations. However, both anatomical and physiological studies have indicated the presence of NMDA receptors located presynaptically. Physiological studies of p...

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Autores principales:	Seena S Mathew, John J Hablitz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eb61d9461a5948588a594c570035ae64
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spelling	oai:doaj.org-article:eb61d9461a5948588a594c570035ae642021-11-18T06:58:32ZPresynaptic NMDA receptors mediate IPSC potentiation at GABAergic synapses in developing rat neocortex.1932-620310.1371/journal.pone.0017311https://doaj.org/article/eb61d9461a5948588a594c570035ae642011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21365001/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>NMDA receptors are traditionally viewed as being located postsynaptically, at both synaptic and extrasynaptic locations. However, both anatomical and physiological studies have indicated the presence of NMDA receptors located presynaptically. Physiological studies of presynaptic NMDA receptors on neocortical GABAergic terminals and their possible role in synaptic plasticity are lacking.<h4>Methodology/principal findings</h4>We report here that presynaptic NMDA receptors are present on GABAergic terminals in developing (postnatal day (PND) 12-15) but not older (PND21-25) rat frontal cortex. Using MK-801 in the recording pipette to block postsynaptic NMDA receptors, evoked and miniature IPSCs were recorded in layer II/III pyramidal cells in the presence of AMPA/KA receptor antagonists. Bath application of NMDA or NMDA receptor antagonists produced increases and decreases in mIPSC frequency, respectively. Physiologically patterned stimulation (10 bursts of 10 stimuli at 25 Hz delivered at 1.25 Hz) induced potentiation at inhibitory synapses in PND12-15 animals. This consisted of an initial rapid, large increase in IPSC amplitude followed by a significant but smaller persistent increase. Similar changes were not observed in PND21-25 animals. When 20 mM BAPTA was included in the recording pipette, potentiation was still observed in the PND12-15 group indicating that postsynaptic increases in calcium were not required. Potentiation was not observed when patterned stimulation was given in the presence of D-APV or the NR2B subunit antagonist Ro25-6981.<h4>Conclusions/significance</h4>The present results indicate that presynaptic NMDA receptors modulate GABA release onto neocortical pyramidal cells. Presynaptic NR2B subunit containing NMDA receptors are also involved in potentiation at developing GABAergic synapses in rat frontal cortex. Modulation of inhibitory GABAergic synapses by presynaptic NMDA receptors may be important for proper functioning of local cortical networks during development.Seena S MathewJohn J HablitzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e17311 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Seena S Mathew John J Hablitz Presynaptic NMDA receptors mediate IPSC potentiation at GABAergic synapses in developing rat neocortex.
description	<h4>Background</h4>NMDA receptors are traditionally viewed as being located postsynaptically, at both synaptic and extrasynaptic locations. However, both anatomical and physiological studies have indicated the presence of NMDA receptors located presynaptically. Physiological studies of presynaptic NMDA receptors on neocortical GABAergic terminals and their possible role in synaptic plasticity are lacking.<h4>Methodology/principal findings</h4>We report here that presynaptic NMDA receptors are present on GABAergic terminals in developing (postnatal day (PND) 12-15) but not older (PND21-25) rat frontal cortex. Using MK-801 in the recording pipette to block postsynaptic NMDA receptors, evoked and miniature IPSCs were recorded in layer II/III pyramidal cells in the presence of AMPA/KA receptor antagonists. Bath application of NMDA or NMDA receptor antagonists produced increases and decreases in mIPSC frequency, respectively. Physiologically patterned stimulation (10 bursts of 10 stimuli at 25 Hz delivered at 1.25 Hz) induced potentiation at inhibitory synapses in PND12-15 animals. This consisted of an initial rapid, large increase in IPSC amplitude followed by a significant but smaller persistent increase. Similar changes were not observed in PND21-25 animals. When 20 mM BAPTA was included in the recording pipette, potentiation was still observed in the PND12-15 group indicating that postsynaptic increases in calcium were not required. Potentiation was not observed when patterned stimulation was given in the presence of D-APV or the NR2B subunit antagonist Ro25-6981.<h4>Conclusions/significance</h4>The present results indicate that presynaptic NMDA receptors modulate GABA release onto neocortical pyramidal cells. Presynaptic NR2B subunit containing NMDA receptors are also involved in potentiation at developing GABAergic synapses in rat frontal cortex. Modulation of inhibitory GABAergic synapses by presynaptic NMDA receptors may be important for proper functioning of local cortical networks during development.
format	article
author	Seena S Mathew John J Hablitz
author_facet	Seena S Mathew John J Hablitz
author_sort	Seena S Mathew
title	Presynaptic NMDA receptors mediate IPSC potentiation at GABAergic synapses in developing rat neocortex.
title_short	Presynaptic NMDA receptors mediate IPSC potentiation at GABAergic synapses in developing rat neocortex.
title_full	Presynaptic NMDA receptors mediate IPSC potentiation at GABAergic synapses in developing rat neocortex.
title_fullStr	Presynaptic NMDA receptors mediate IPSC potentiation at GABAergic synapses in developing rat neocortex.
title_full_unstemmed	Presynaptic NMDA receptors mediate IPSC potentiation at GABAergic synapses in developing rat neocortex.
title_sort	presynaptic nmda receptors mediate ipsc potentiation at gabaergic synapses in developing rat neocortex.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/eb61d9461a5948588a594c570035ae64
work_keys_str_mv	AT seenasmathew presynapticnmdareceptorsmediateipscpotentiationatgabaergicsynapsesindevelopingratneocortex AT johnjhablitz presynapticnmdareceptorsmediateipscpotentiationatgabaergicsynapsesindevelopingratneocortex
_version_	1718424141606944768

Presynaptic NMDA receptors mediate IPSC potentiation at GABAergic synapses in developing rat neocortex.

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