Acute stress causes rapid synaptic insertion of Ca2+-permeable AMPA receptors to facilitate long-term potentiation in the hippocampus

Abstract

The neuroendocrine response to episodes of acute stress is crucial for survival whereas the prolonged response to chronic stress can be detrimental. Learning and memory are particularly susceptible to stress with cognitive deficits being well characterized consequences of chronic stress. Although there is good evidence that acute stress can enhance cognitive performance, the mechanism(s) for this are unclear. We find that hippocampal slices, either prepared from rats following 30 min restraint stress or directly exposed to glucocorticoids, exhibit an N-methyl-d-aspartic acid receptor-independent form of long-term potentiation. We demonstrate that the mechanism involves an NMDA receptor and PKA-dependent insertion of Ca2+-permeable AMPA receptors into synapses. These then trigger the additional NMDA receptor-independent form of LTP during high frequency stimulation.

Induction and Expression of Fear Sensitization Caused by Acute Traumatic Stress

“…Therefore, an increase in AMPAR subunits but not NMDAR subunits 2 weeks after the stressor is consistent with these findings. Similar results have been found in the hippocampus, where surface increases in GluA1 but not GluA2 occurred after restraint stress (Whitehead et al, 2013). AMPAR lacking GluA2 have high relative calcium permeability, whereas permeability of AMPAR containing GluA2 is very low; the former enhances cell excitability (Hollmann et al, 1991).…”

“…Induction and maintenance of longterm potentiation requires the insertion of GluA1-containing AMPAR in the synapse. Although the process is induced by stress hormones (ie, glucocorticoids), maintenance of AMPAR at the synapse involve both protein kinase A-mediated phosphorylation and endosomal recycling (Kessels and Malinow, 2009;Hanley, 2010;Whitehead et al, 2013). Preventing the upregulation of GluA1 after the 15-shock stressor or perhaps blocking this synaptic AMPAR maintenance may prevent SEFL from developing following a stressor.…”

Network compensation of cyclic GMP-dependent protein kinase II knockout in the hippocampus by Ca 2+ -permeable AMPA receptors

“…Several studies suggest that LTP is increased when CPARs are present in the hippocampus compared with WT (16,(24)(25)(26). Because we found synaptic expression of CPARs in KO hippocampal neurons, we hypothesized that CPAR expression could compensate in the KO for LTP impairment found when cGKII is acutely inhibited.…”

“…CPAR-mediated hippocampal LTP has been found in several conditions, including in the GluA2 KO (24,25,30) and following calcineurin inhibition (16,23) and acute stress (26). The CPARmediated LTP is functionally distinct from classical NMDARmediated LTP (24)(25)(26)30).…”

Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics

“…Moreover, acute stress enhances a NMDA receptorindependent form of LTP by mobilising calcium-permeable AMPA receptors in a GCdependent manner (Popoli et al, 2011). The duration of this MR-dependent upregulation of glutamatergic neurotransmission is region-specific, since it's shortlasting at the hippocampal level but long-lasting in the basolateral amygdala, where subsequent acute stressful insults lead to a GR-dependent down-regulation of glutamatergic stimulation (Whitehead et al, 2013). In distinction to this there is a brain region-specific adaptation of glutamate release in relation to chronic stress or to acute insults after chronic stress, since in some parts of the corticolimbic system (i.e.…”