Principles of long-term dynamics of dendritic spines.

Long-term potentiation of synapse strength requires enlargement of dendritic spines on cerebral pyramidal neurons. Long-term depression is linked to spine shrinkage. Indeed, spines are dynamic structures: they form, change their shapes and volumes, or can disappear in the space of hours.

Structure-stability-function relationships of dendritic spines.

Dendritic spines, which receive most of the excitatory synaptic input in the cerebral cortex, are heterogeneous with regard to their structure, stability and function. Spines with large heads are stable, express large numbers of AMPA-type glutamate receptors, and contribute to strong synaptic connections. By contrast, spines with small heads are motile and unstable and contribute to weak or silent synaptic connections.

Hippocampal cytochrome P450s synthesize brain neurosteroids which are paracrine neuromodulators of synaptic signal transduction.

Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, 17beta-estradiol and testosterone as well as their sulfate esters. These brain neurosteroids are synthesized by cytochrome P450s (P450scc, P45017alpha and P450arom) from endogenous cholesterol. Synthesis is acutely dependent on the Ca(2+) influx attendant upon neuron-neuron communication via N-methyl-D-aspartate (NMDA) receptors.

Corticosterone acutely prolonged N-methyl-d-aspartate receptor-mediated Ca2+ elevation in cultured rat hippocampal neurons.

This work reports the first demonstration that corticosterone (CORT) has a rapid and transient effect on NMDA receptor-mediated Ca2+ signaling in cultured rat hippocampal neurons. Using single cell Ca2+ imaging, CORT and agonists of glucocorticoid receptors were observed to modulate the NMDA receptor-mediated Ca2+ signals in a completely different fashion from pregnenolone sulfate. In the absence of steroids, 100 micro m NMDA induced a transient Ca2+ signal that lasted for 30-70 s in 86.

[Dendritic spine structures and functions].

Glutamate sensitivities of single dendritic spines were investigated with a two-photon photolysis of a caged-glutamate compound and the patch-clamp method in mouse hippocampal slice preparations. We found that the fast glutamate responses mediated by AMPA receptors were proportional to the volume of the spine head, but the slow responses induced by NMDA receptors displayed only weak correlation with the spine head volume and were independently regulated with the expression of AMPA receptors. This indicates that the strength of synaptic connection is stored as the spine structures, but that its plasticity may be regulated by independent factors.