PMID- 23554474
OWN - NLM
STAT- MEDLINE
DCOM- 20130528
LR  - 20211021
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 33
IP  - 14
DP  - 2013 Apr 3
TI  - Histone deacetylase 2 cell autonomously suppresses excitatory and enhances 
      inhibitory synaptic function in CA1 pyramidal neurons.
PG  - 5924-9
LID - 10.1523/JNEUROSCI.3162-12.2013 [doi]
AB  - Histone deacetylase 2 (HDAC2) negatively regulates excitatory synapse number and 
      memory performance. However, whether HDAC2 regulation of excitatory synapses 
      occurs in a cell-autonomous manner and whether HDAC2 regulates inhibitory 
      synaptic functions are not well understood. To examine these aspects of HDAC2 
      function, we used sparse transfection of rat hippocampal slice cultures and 
      whole-cell recordings in pyramidal neurons. HDAC2 knockdown (KD) in single 
      postsynaptic pyramidal neurons enhanced, whereas HDAC2 overexpression (OE) 
      reduced, excitatory synaptic transmission. Postsynaptic KD of HDAC2 also 
      facilitated expression of long-term potentiation induced by subthreshold 
      induction stimuli, without altering long-term depression. In contrast, HDAC2 KD 
      reduced, whereas HDAC2 OE enhanced, inhibitory synaptic transmission. Alterations 
      of postsynaptic GABA(A) receptors (GABA(A)Rs) likely underlie the impact of HDAC2 
      on inhibitory transmission. Consistent with this, we observed reduced transcript 
      and protein levels of the GABA(A)R gamma2 subunit and reduced surface expression of 
      the alpha2 subunit after HDAC2 KD. Furthermore, we observed a reduction in synaptic 
      but not tonic GABA(A)R currents by HDAC2 KD, suggesting that HDAC2 selectively 
      affects synaptic abundance of functional GABA(A)Rs. Immunostaining for 
      postsynaptic GABA(A)Rs confirmed that HDAC2 KD and OE can regulate the synaptic 
      abundance of these receptors. Together, these results highlight a role for HDAC2 
      in suppressing synaptic excitation and enhancing synaptic inhibition of 
      hippocampal neurons. Therefore, a shift in the balance of synaptic excitation 
      versus inhibition favoring excitation could contribute to the beneficial effects 
      of reducing HDAC2 function in wild-type mice or of inhibiting HDACs in models of 
      cognitive impairment.
FAU - Hanson, Jesse E
AU  - Hanson JE
AD  - Department of Neuroscience, Genentech, South San Francisco, California 94080, 
      USA.
FAU - Deng, Lunbin
AU  - Deng L
FAU - Hackos, David H
AU  - Hackos DH
FAU - Lo, Shih-Ching
AU  - Lo SC
FAU - Lauffer, Benjamin E
AU  - Lauffer BE
FAU - Steiner, Pascal
AU  - Steiner P
FAU - Zhou, Qiang
AU  - Zhou Q
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Protein Subunits)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, GABA-A)
RN  - 0 (Slc32a1 protein, rat)
RN  - 0 (Vesicular Inhibitory Amino Acid Transport Proteins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 3.5.1.98 (HDAC1 protein, human)
RN  - EC 3.5.1.98 (Histone Deacetylase 1)
RN  - EC 3.5.1.98 (Histone Deacetylase 2)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - CA1 Region, Hippocampal/*cytology
MH  - Cell Line, Transformed
MH  - Electric Stimulation
MH  - Excitatory Postsynaptic Potentials/drug effects/genetics/*physiology
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Green Fluorescent Proteins/genetics
MH  - Histone Deacetylase 1/genetics/metabolism
MH  - Histone Deacetylase 2/genetics/*metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Inhibitory Postsynaptic Potentials/drug effects/genetics/*physiology
MH  - Male
MH  - Neurons
MH  - Neurotransmitter Agents/pharmacology
MH  - Patch-Clamp Techniques
MH  - Protein Subunits/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, GABA-A/metabolism
MH  - Transfection
MH  - Vesicular Inhibitory Amino Acid Transport Proteins/metabolism
PMC - PMC6618922
EDAT- 2013/04/05 06:00
MHDA- 2013/05/29 06:00
PMCR- 2013/10/03
CRDT- 2013/04/05 06:00
PHST- 2013/04/05 06:00 [entrez]
PHST- 2013/04/05 06:00 [pubmed]
PHST- 2013/05/29 06:00 [medline]
PHST- 2013/10/03 00:00 [pmc-release]
AID - 33/14/5924 [pii]
AID - 3827928 [pii]
AID - 10.1523/JNEUROSCI.3162-12.2013 [doi]
PST - ppublish
SO  - J Neurosci. 2013 Apr 3;33(14):5924-9. doi: 10.1523/JNEUROSCI.3162-12.2013.