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Synapse composition and organization following chronic activity blockade in cultured hippocampal neurons
Author(s) -
Harms Kimberly J.,
Craig Ann Marie
Publication year - 2005
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.20635
Subject(s) - postsynaptic potential , biology , excitatory synapse , synapse , postsynaptic density , neuroscience , excitatory postsynaptic potential , neurotransmission , inhibitory postsynaptic potential , synaptic plasticity , silent synapse , neurotransmitter , glutamate receptor , synaptic augmentation , synaptic fatigue , receptor , ampa receptor , central nervous system , biochemistry
Activity plays multiple roles in the expression of synaptic plasticity, and has been shown to regulate the localization of both neurotransmitter receptors and downstream signaling machinery. However, the role of activity in central synapse formation and organization is incompletely understood. Some studies indicate that synapse formation can occur in the absence of synaptic activity, while others indicate that activity is required for synapse maintenance and receptor recruitment. In addition, the effects of long‐term blockade of transmission generally, rather than blockade of specific receptors, on postsynaptic protein complement has been poorly characterized. In order to address the role of activity in synapse formation and postsynaptic specialization, we used tetanus toxin to chronically cleave VAMP2 and inhibit SNARE‐mediated neurotransmitter release in cultured hippocampal neurons. Although these neurons are deficient in synaptic release, they are of normal size and morphology. In addition, both excitatory and inhibitory synapses form along their processes with normal density. These synapses have a remarkably similar cellular and molecular organization compared to controls, and are capable of recruiting postsynaptic scaffolding proteins, GABA, and glutamate receptors. Subcellular enrichment of synaptic proteins into specialized domains also appears intact. These data indicate that global activity inhibition is insufficient to disrupt central synapse formation or organization. J. Comp. Neurol. 490:72–84, 2005. © 2005 Wiley‐Liss, Inc.