The rodent adrenal hormone corticosterone (CORT) reaches the brain in hourly ultradian pulses, with a steep rise in amplitude before awakening. The impact of a single CORT pulse on glutamatergic transmission is well documented, but it remains poorly understood how consecutive pulses impact on glutamate receptor trafficking and synaptic plasticity. By using high-resolution imaging and electrophysiological approaches, we report that a single pulse of CORT to hippocampal networks causes synaptic enrichment of glutamate receptors and increased responses to spontaneously released glutamatergic vesicles, collectively abrogating the ability to subsequently induce synaptic long-term potentiation. Strikingly, a second pulse of CORT one hour after the firstmimicking ultradian pulses-completely normalizes all aspects of glutamate transmission investigated, restoring the plastic range of the synapse. The effect of the second pulse is precisely timed and depends on a nongenomic glucocorticoid receptor-dependent pathway. This normalizing effect through a sequence of CORT pulsesas seen around awakening-may ensure that hippocampal glutamatergic synapses remain fully responsive and able to encode new stress-related information when daily activities start.hippocampus | AMPA receptor trafficking
Corticosterone activates two types of intracellular receptors in the rodent brain: the high affinity mineralocorticoid receptor (MR) and lower affinity glucocorticoid receptor (GR). These receptors act as transcriptional regulators and mediate slow changes in neuronal activity in a region-dependent manner. For example, in CA1 pyramidal cells, corticosterone slowly changes Ca(2+) currents and glutamate transmission but dentate granule cells appear to be resistant. Recent studies have shown that corticosteroids also exert rapid MR-dependent, nongenomic effects on hippocampal CA1 cells [e.g. increasing the frequency of miniature excitatory postsynaptic currents (mEPSCs)]. In the present study, we investigated whether dentate granule cells are also resistant to the rapid effects of corticosterone. We found that, comparable to the CA1 area, corticosterone quickly and reversibly increases mEPSC frequency but not amplitude of dentate cells. This effect did not require protein synthesis and displayed the pharmacological profile of an MR- rather than GR-dependent event. These data support the hypothesis that, unlike the slow gene-mediated effects of corticosterone, rapid hormonal actions are quite similar for CA1 and dentate cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.