TY - JOUR
T1 - Synaptogenesis on mature hippocampal dendrites occurs via filopodia and immature spines during blocked synaptic transmission
AU - Petrak, Lara J.
AU - Harris, Kristen M.
AU - Kirov, Sergei A.
PY - 2005/4/4
Y1 - 2005/4/4
N2 - During development, dendritic spines emerge as stubby protrusions from single synapses on dendritic shafts or from retracting filopodia, many of which have more than one synapse. These structures are rarely encountered in the mature brain. Recently, confocal and two-photon microscopy have revealed a proliferation of new filopodia-like protrusions in mature hippocampal slices, especially when synaptic transmission was blocked. It was not known whether these protrusions have synapses nor whether they are accompanied by the other immature spine forms. Here, reconstruction from serial section electron microscopy (ssEM) was used to answer these questions. Acute hippocampal slices from mature male rats, ages 56 and 63 days, were maintained in vitro in control medium or in a nominally calcium-free medium with high magnesium, glutamate receptor antagonists, and sodium and calcium channel blockers. At the end of each 8-hour experiment, all slices were fixed, coded, and processed for ssEM. In agreement with light microscopy, there were more filopodia along dendrites in slices with blocked synaptic transmission. These filopodia were identified by their pointy tips and either the absence of synapses or presence of multiple synapses along them. There was also a proliferation of stubby spines. Filopodia along mature dendrites were typically shorter than developmental filopodia, with outgrowth likely being constrained by reduced extracellular space and compact neuropil, providing numerous candidate presynaptic partners in the vicinity of the mature dendrites. These findings suggest that synaptogenesis and spine formation are readily initiated under conditions of reduced activity in the mature brain.
AB - During development, dendritic spines emerge as stubby protrusions from single synapses on dendritic shafts or from retracting filopodia, many of which have more than one synapse. These structures are rarely encountered in the mature brain. Recently, confocal and two-photon microscopy have revealed a proliferation of new filopodia-like protrusions in mature hippocampal slices, especially when synaptic transmission was blocked. It was not known whether these protrusions have synapses nor whether they are accompanied by the other immature spine forms. Here, reconstruction from serial section electron microscopy (ssEM) was used to answer these questions. Acute hippocampal slices from mature male rats, ages 56 and 63 days, were maintained in vitro in control medium or in a nominally calcium-free medium with high magnesium, glutamate receptor antagonists, and sodium and calcium channel blockers. At the end of each 8-hour experiment, all slices were fixed, coded, and processed for ssEM. In agreement with light microscopy, there were more filopodia along dendrites in slices with blocked synaptic transmission. These filopodia were identified by their pointy tips and either the absence of synapses or presence of multiple synapses along them. There was also a proliferation of stubby spines. Filopodia along mature dendrites were typically shorter than developmental filopodia, with outgrowth likely being constrained by reduced extracellular space and compact neuropil, providing numerous candidate presynaptic partners in the vicinity of the mature dendrites. These findings suggest that synaptogenesis and spine formation are readily initiated under conditions of reduced activity in the mature brain.
KW - Dendritic spines
KW - Mature CA1 neurons
KW - Serial section electron microscopy
KW - Spinogenesis
KW - Structural synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=14644415956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14644415956&partnerID=8YFLogxK
U2 - 10.1002/cne.20468
DO - 10.1002/cne.20468
M3 - Article
C2 - 15736233
AN - SCOPUS:14644415956
SN - 0021-9967
VL - 484
SP - 183
EP - 190
JO - Journal of Comparative Neurology
JF - Journal of Comparative Neurology
IS - 2
ER -