Erschienen in:Proceedings of the National Academy of Sciences of the United States of America
Sprache:
Englisch
DOI:
10.1073/pnas.1411216111
ISSN:
0027-8424
Entstehung:
Anmerkungen:
Beschreibung:
<p>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 first—mimicking 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 pulses—as seen around awakening—may ensure that hippocampal glutamatergic synapses remain fully responsive and able to encode new stress-related information when daily activities start.</p>