PMID- 23055515
OWN - NLM
STAT- MEDLINE
DCOM- 20130103
LR  - 20220129
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 32
IP  - 41
DP  - 2012 Oct 10
TI  - Endocannabinoid-mediated long-term depression of afferent excitatory synapses in 
      hippocampal pyramidal cells and GABAergic interneurons.
PG  - 14448-63
LID - 10.1523/JNEUROSCI.1676-12.2012 [doi]
AB  - Although endocannabinoids have emerged as essential retrograde messengers in 
      several forms of synaptic plasticity, it remains controversial whether they 
      mediate long-term depression (LTD) of glutamatergic synapses onto excitatory and 
      inhibitory neurons in the hippocampus. Here, we show that parvalbumin- and 
      somatostatin/metabotropic glutamate receptor 1(a) (mGlu(1a))-positive GABAergic 
      interneurons express diacylglycerol lipase-alpha (DGL-alpha), a synthesizing enzyme of 
      the endocannabinoid 2-arachidonoylglycerol (2-AG), albeit at lower levels than 
      principal cells. Moreover, this lipase accumulates postsynaptically around 
      afferent excitatory synapses in all three cell types. To address the role of 
      retrograde 2-AG signaling in LTD, we investigated two forms: (1) produced by 
      postsynaptic spiking paired with subsequent presynaptic stimulation or (2) 
      induced by group I mGlu activation by (S)-3,5-dihydroxyphenylglycine (DHPG). 
      Neither form of LTD was evoked in the presence of the mGlu(5) antagonist MPEP 
      [2-methyl-6-(phenylethynyl)-pyridine], the DGL inhibitor THL [N-formyl-l-leucine 
      (1S)-1-[[(2S,3S)-3-hexyl-4-oxo-2-oxetanyl]methyl]dodecyl ester], or the 
      intracellularly applied Ca(2+) chelator BAPTA in CA1 pyramidal cells, 
      fast-spiking interneurons (representing parvalbumin-containing cells) and 
      interneurons projecting to stratum lacunosum-moleculare (representing 
      somatostatin/mGlu(1a)-expressing interneurons). Both forms of LTD were completely 
      absent in CB(1) cannabinoid receptor knock-out mice, whereas pharmacological 
      blockade of CB(1) led to inconsistent results. Notably, in accordance with their 
      lower DGL-alpha level, a higher stimulation frequency or higher DHPG concentration 
      was required for LTD induction in interneurons compared with pyramidal cells. 
      These findings demonstrate that hippocampal principal cells and interneurons 
      produce endocannabinoids to mediate LTD in a qualitatively similar, but 
      quantitatively different manner. The shifted induction threshold implies that 
      endocannabinoid-LTD contributes to cortical information processing during 
      distinct network activity patterns in a cell type-specific manner.
FAU - Peterfi, Zoltan
AU  - Peterfi Z
AD  - Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 
      Budapest, Hungary.
FAU - Urban, Gabriella M
AU  - Urban GM
FAU - Papp, Orsolya I
AU  - Papp OI
FAU - Nemeth, Beata
AU  - Nemeth B
FAU - Monyer, Hannah
AU  - Monyer H
FAU - Szabo, Gabor
AU  - Szabo G
FAU - Erdelyi, Ferenc
AU  - Erdelyi F
FAU - Mackie, Ken
AU  - Mackie K
FAU - Freund, Tamas F
AU  - Freund TF
FAU - Hajos, Norbert
AU  - Hajos N
FAU - Katona, Istvan
AU  - Katona I
LA  - eng
GR  - R01 DA011322/DA/NIDA NIH HHS/United States
GR  - P01 DA009158/DA/NIDA NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - DA009158/DA/NIDA NIH HHS/United States
GR  - 090946/WT_/Wellcome Trust/United Kingdom
GR  - DA0216969/DA/NIDA NIH HHS/United States
GR  - 243153/ERC_/European Research Council/International
GR  - DA011322/DA/NIDA NIH HHS/United States
GR  - K05 DA021696/DA/NIDA NIH HHS/United States
GR  - DA09158/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Endocannabinoids)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
SB  - IM
MH  - Animals
MH  - Endocannabinoids/*physiology
MH  - Excitatory Postsynaptic Potentials/*physiology
MH  - Hippocampus/cytology/physiology
MH  - Interneurons/physiology
MH  - Long-Term Synaptic Depression/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurons, Afferent/physiology
MH  - Pyramidal Cells/*physiology
MH  - Synapses/*physiology
MH  - gamma-Aminobutyric Acid/*physiology
PMC - PMC3494839
MID - EMS50184
OID - NLM: EMS50184
EDAT- 2012/10/12 06:00
MHDA- 2013/01/04 06:00
PMCR- 2013/04/10
CRDT- 2012/10/12 06:00
PHST- 2012/10/12 06:00 [entrez]
PHST- 2012/10/12 06:00 [pubmed]
PHST- 2013/01/04 06:00 [medline]
PHST- 2013/04/10 00:00 [pmc-release]
AID - 32/41/14448 [pii]
AID - 3804333 [pii]
AID - 10.1523/JNEUROSCI.1676-12.2012 [doi]
PST - ppublish
SO  - J Neurosci. 2012 Oct 10;32(41):14448-63. doi: 10.1523/JNEUROSCI.1676-12.2012.