PMID- 11517266
OWN - NLM
STAT- MEDLINE
DCOM- 20010920
LR  - 20220317
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 21
IP  - 17
DP  - 2001 Sep 1
TI  - Rab3A is required for brain-derived neurotrophic factor-induced synaptic 
      plasticity: transcriptional analysis at the population and single-cell levels.
PG  - 6782-90
AB  - Brain-derived neurotrophic factor (BDNF) modulates synaptic strength in 
      hippocampal neurons, in addition to promoting survival and differentiation. To 
      identify genes involved in trophic regulation of synaptic plasticity, we have 
      used a multidisciplinary approach of differential display and family-specific 
      slot blots in combination with whole-cell patch-clamp recordings of dissociated 
      hippocampal neurons. Three hour exposure to BDNF elicited a 2.6-fold increase in 
      synaptic charge and a concomitant induction of 11 genes as revealed by 
      differential display, including the small GTP-binding vesicular trafficking 
      protein Rab3A and the enzyme guanylate cyclase (GC). Slot blot analysis on a 
      population of neurons confirmed an average of 3.1-fold induction of these clones. 
      In contrast, individual pyramidal-like neurons that were first characterized 
      electrophysiologically in the presence of BDNF and subjected to transcriptional 
      analysis displayed more robust increases (4.8-fold), emphasizing the neuronal 
      heterogeneity. Transcriptional changes of Rab3A and GC were accompanied by 
      translational regulation, shown by Western blot analysis. Furthermore, a number 
      of GC-associated and Rab3A effector molecules were induced by BDNF at either the 
      gene or protein levels. The functional role of Rab3A in BDNF-induced synaptic 
      plasticity was assessed using cells derived from Rab3A knock-out mice. These 
      neurons failed to show an increase in synaptic charge in response to BDNF at 10 
      min; however a late response to BDNF was detected at 20 min. This late response 
      was similar in time course to that induced by postsynaptic activation of 
      glutamate receptors. Our results demonstrate a requirement for Rab3A and may 
      reveal a temporal distinction between presynaptic and postsynaptic mechanisms of 
      BDNF-induced synaptic plasticity associated with learning and memory.
FAU - Thakker-Varia, S
AU  - Thakker-Varia S
AD  - Department of Neuroscience and Cell Biology, University of Medicine and Dentistry 
      of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 
      08854-5635, USA.
FAU - Alder, J
AU  - Alder J
FAU - Crozier, R A
AU  - Crozier RA
FAU - Plummer, M R
AU  - Plummer MR
FAU - Black, I B
AU  - Black IB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Glutamate)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 3.6.5.2 (rab3A GTP-Binding Protein)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology
MH  - Cells, Cultured
MH  - Clone Cells/cytology/metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation/drug effects
MH  - Glutamic Acid/pharmacology
MH  - Guanylate Cyclase/genetics/metabolism
MH  - Hippocampus/cytology/embryology
MH  - Mice
MH  - Mice, Knockout
MH  - Neuronal Plasticity/drug effects/*physiology
MH  - Neurons/cytology/drug effects/metabolism
MH  - Patch-Clamp Techniques
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Reaction Time/drug effects/genetics
MH  - Receptors, Glutamate/metabolism
MH  - Synapses/drug effects/*metabolism
MH  - *Transcription, Genetic
MH  - rab3A GTP-Binding Protein/deficiency/genetics/*metabolism
PMC - PMC6763088
EDAT- 2001/08/23 10:00
MHDA- 2001/09/21 10:01
PMCR- 2002/03/01
CRDT- 2001/08/23 10:00
PHST- 2001/08/23 10:00 [pubmed]
PHST- 2001/09/21 10:01 [medline]
PHST- 2001/08/23 10:00 [entrez]
PHST- 2002/03/01 00:00 [pmc-release]
AID - 21/17/6782 [pii]
AID - 5594 [pii]
AID - 10.1523/JNEUROSCI.21-17-06782.2001 [doi]
PST - ppublish
SO  - J Neurosci. 2001 Sep 1;21(17):6782-90. doi: 10.1523/JNEUROSCI.21-17-06782.2001.