Abstract
The precise contribution of the cadherin-β-catenin synapse adhesion complex in the functional and structural changes associated with the pre- and postsynaptic terminals remains unclear. Here we report a requirement for endogenous β-catenin in regulating synaptic strength and dendritic spine morphology in cultured hippocampal pyramidal neurons. Ablating β-catenin after the initiation of synaptogenesis in the postsynaptic neuron reduces the amplitude of spontaneous excitatory synaptic responses without a concurrent change in their frequency and synapse density. The normal glutamatergic synaptic response is maintained by postsynaptic β-catenin in a cadherin-dependent manner and requires the C-terminal PDZ-binding motif of β-catenin but not the link to the actin cytoskeleton. In addition, ablating β-catenin in postsynaptic neurons accompanies a block of bidirectional quantal scaling of glutamatergic responses induced by chronic activity manipulation. In older cultures at a time when neurons have abundant dendritic spines, neurons ablated for β-catenin show thin, elongated spines and reduced proportion of mushroom spines without a change in spine density. Collectively, these findings suggest that the cadherin-β-catenin complex is an integral component of synaptic strength regulation and plays a basic role in coupling synapse function and spine morphology.
| Original language | English |
|---|---|
| Pages (from-to) | 13479-13484 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 104 |
| Issue number | 33 |
| DOIs | |
| Publication status | Published - 2007 Aug 14 |
| Externally published | Yes |
Fingerprint
Keywords
- α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors
- Quantal scaling
- Spine morphology
- Synapse adhesion proteins
ASJC Scopus subject areas
- Genetics
- General
Cite this
β-Catenin regulates excitatory postsynaptic strength at hippocampal synapses. / Okuda, Takashi; Yu, Lily M Y; Cingolani, Lorenzo A.; Kemler, Rolf; Goda, Yukiko.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 33, 14.08.2007, p. 13479-13484.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - β-Catenin regulates excitatory postsynaptic strength at hippocampal synapses
AU - Okuda, Takashi
AU - Yu, Lily M Y
AU - Cingolani, Lorenzo A.
AU - Kemler, Rolf
AU - Goda, Yukiko
PY - 2007/8/14
Y1 - 2007/8/14
N2 - The precise contribution of the cadherin-β-catenin synapse adhesion complex in the functional and structural changes associated with the pre- and postsynaptic terminals remains unclear. Here we report a requirement for endogenous β-catenin in regulating synaptic strength and dendritic spine morphology in cultured hippocampal pyramidal neurons. Ablating β-catenin after the initiation of synaptogenesis in the postsynaptic neuron reduces the amplitude of spontaneous excitatory synaptic responses without a concurrent change in their frequency and synapse density. The normal glutamatergic synaptic response is maintained by postsynaptic β-catenin in a cadherin-dependent manner and requires the C-terminal PDZ-binding motif of β-catenin but not the link to the actin cytoskeleton. In addition, ablating β-catenin in postsynaptic neurons accompanies a block of bidirectional quantal scaling of glutamatergic responses induced by chronic activity manipulation. In older cultures at a time when neurons have abundant dendritic spines, neurons ablated for β-catenin show thin, elongated spines and reduced proportion of mushroom spines without a change in spine density. Collectively, these findings suggest that the cadherin-β-catenin complex is an integral component of synaptic strength regulation and plays a basic role in coupling synapse function and spine morphology.
AB - The precise contribution of the cadherin-β-catenin synapse adhesion complex in the functional and structural changes associated with the pre- and postsynaptic terminals remains unclear. Here we report a requirement for endogenous β-catenin in regulating synaptic strength and dendritic spine morphology in cultured hippocampal pyramidal neurons. Ablating β-catenin after the initiation of synaptogenesis in the postsynaptic neuron reduces the amplitude of spontaneous excitatory synaptic responses without a concurrent change in their frequency and synapse density. The normal glutamatergic synaptic response is maintained by postsynaptic β-catenin in a cadherin-dependent manner and requires the C-terminal PDZ-binding motif of β-catenin but not the link to the actin cytoskeleton. In addition, ablating β-catenin in postsynaptic neurons accompanies a block of bidirectional quantal scaling of glutamatergic responses induced by chronic activity manipulation. In older cultures at a time when neurons have abundant dendritic spines, neurons ablated for β-catenin show thin, elongated spines and reduced proportion of mushroom spines without a change in spine density. Collectively, these findings suggest that the cadherin-β-catenin complex is an integral component of synaptic strength regulation and plays a basic role in coupling synapse function and spine morphology.
KW - α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors
KW - Quantal scaling
KW - Spine morphology
KW - Synapse adhesion proteins
UR - http://www.scopus.com/inward/record.url?scp=34548058077&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548058077&partnerID=8YFLogxK
U2 - 10.1073/pnas.0702334104
DO - 10.1073/pnas.0702334104
M3 - Article
C2 - 17679699
AN - SCOPUS:34548058077
VL - 104
SP - 13479
EP - 13484
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 33
ER -