Postnatal synaptic potentiation: Delivery of GluR4-containing AMPA receptors
by spontaneous activity
J. Julius Zhu1, 3, José A. Esteban1, 3, Yasunori Hayashi2
& Roberto Malinow1
1
Cold Spring Harbor Laboratory, 1 Bungtown
Road, Cold Spring Harbor, New York 11724
, USA
2
Center for Learning and Memory, Massachusetts Institute
of Technology, Cambridge, Massachusetts 02139
, USA
3
The first two authors contributed equally to this work
Correspondence should be addressed to Roberto Malinow malinow@cshl.org
To examine how functional circuits are established in the brain, we studied
excitatory transmission in early postnatal hippocampus. Spontaneous neural
activity was sufficient to selectively deliver GluR4-containing AMPA receptors
(AMPA-Rs) into synapses. This delivery allowed non-functional connections
to transmit at resting potentials and required NMDA receptors (NMDA-Rs) but
not CaMKII activation. Subsequently, these delivered receptors were exchanged
with non-synaptic GluR2-containing AMPA-Rs in a manner requiring little neuronal
activity. The enhanced transmission resulting from this delivery and subsequent
exchange was maintained for at least several days and required an interaction
between GluR2 and NSF. Thus, this sequence of subunit-specific trafficking
events triggered by spontaneous activity in early postnatal development may
be crucial for initial establishment of long-lasting functional circuitry.
