PMID- 27443506
OWN - NLM
STAT- MEDLINE
DCOM- 20180529
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Jul 22
TI  - Cdk5 Modulates Long-Term Synaptic Plasticity and Motor Learning in Dorsolateral 
      Striatum.
PG  - 29812
LID - 10.1038/srep29812 [doi]
LID - 29812
AB  - The striatum controls multiple cognitive aspects including motivation, reward 
      perception, decision-making and motor planning. In particular, the dorsolateral 
      striatum contributes to motor learning. Here we define an approach for 
      investigating synaptic plasticity in mouse dorsolateral cortico-striatal 
      circuitry and interrogate the relative contributions of neurotransmitter 
      receptors and intracellular signaling components. Consistent with previous 
      studies, we show that long-term potentiation (LTP) in cortico-striatal circuitry 
      is facilitated by dopamine, and requires activation of D1-dopamine receptors, as 
      well as NMDA receptors (NMDAR) and their calcium-dependent downstream effectors, 
      including CaMKII. Moreover, we assessed the contribution of the protein kinase 
      Cdk5, a key neuronal signaling molecule, in cortico-striatal LTP. Pharmacological 
      Cdk5 inhibition, brain-wide Cdk5 conditional knockout, or viral-mediated 
      dorsolateral striatal-specific loss of Cdk5 all impaired dopamine-facilitated LTP 
      or D1-dopamine receptor-facilitated LTP. Selective loss of Cdk5 in dorsolateral 
      striatum increased locomotor activity and attenuated motor learning. Taken 
      together, we report an approach for studying synaptic plasticity in mouse 
      dorsolateral striatum and critically implicate D1-dopamine receptor, NMDAR, Cdk5, 
      and CaMKII in cortico-striatal plasticity. Furthermore, we associate striatal 
      plasticity deficits with effects upon behaviors mediated by this circuitry. This 
      approach should prove useful for the study of the molecular basis of plasticity 
      in the dorsolateral striatum.
FAU - Hernandez, Adan
AU  - Hernandez A
AD  - Departments of Psychiatry, Neurology and Neurotherapeutics and Harold C. Simmons 
      Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, 
      Dallas, TX 75390, USA.
FAU - Tan, Chunfeng
AU  - Tan C
AD  - Departments of Psychiatry, Neurology and Neurotherapeutics and Harold C. Simmons 
      Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, 
      Dallas, TX 75390, USA.
FAU - Mettlach, Gabriel
AU  - Mettlach G
AD  - Departments of Psychiatry, Neurology and Neurotherapeutics and Harold C. Simmons 
      Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, 
      Dallas, TX 75390, USA.
FAU - Pozo, Karine
AU  - Pozo K
AD  - Departments of Psychiatry, Neurology and Neurotherapeutics and Harold C. Simmons 
      Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, 
      Dallas, TX 75390, USA.
FAU - Plattner, Florian
AU  - Plattner F
AD  - Departments of Psychiatry, Neurology and Neurotherapeutics and Harold C. Simmons 
      Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, 
      Dallas, TX 75390, USA.
FAU - Bibb, James A
AU  - Bibb JA
AD  - Departments of Psychiatry, Neurology and Neurotherapeutics and Harold C. Simmons 
      Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, 
      Dallas, TX 75390, USA.
LA  - eng
GR  - P30 DA018343/DA/NIDA NIH HHS/United States
GR  - R01 MH079710/MH/NIMH NIH HHS/United States
GR  - R01 DA033485/DA/NIDA NIH HHS/United States
GR  - R01 NS073855/NS/NINDS NIH HHS/United States
GR  - R01 MH083711/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160722
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Receptors, Dopamine D1)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.22 (Cdk5 protein, mouse)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
MH  - Corpus Striatum/*enzymology
MH  - Cyclin-Dependent Kinase 5/*metabolism
MH  - Dopamine/pharmacology
MH  - Learning/drug effects/*physiology
MH  - Locomotion/drug effects/*physiology
MH  - Long-Term Potentiation/drug effects/*physiology
MH  - Male
MH  - Mice
MH  - Receptors, Dopamine D1/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Synaptic Transmission/drug effects/*physiology
PMC - PMC4957238
EDAT- 2016/07/23 06:00
MHDA- 2018/05/31 06:00
PMCR- 2016/07/22
CRDT- 2016/07/23 06:00
PHST- 2016/04/05 00:00 [received]
PHST- 2016/06/24 00:00 [accepted]
PHST- 2016/07/23 06:00 [entrez]
PHST- 2016/07/23 06:00 [pubmed]
PHST- 2018/05/31 06:00 [medline]
PHST- 2016/07/22 00:00 [pmc-release]
AID - srep29812 [pii]
AID - 10.1038/srep29812 [doi]
PST - epublish
SO  - Sci Rep. 2016 Jul 22;6:29812. doi: 10.1038/srep29812.