Who can translate this to plain english for me?

[PaulyF]

Hello Bluelighters,
Below I have posted the abstract from a very recent publication. I just can't follow it that last paragraph. Want to give it a try? I just can't quite decipher it.
Thanks and Good luck!
Background

Clinical evidence that ketamine, a nonselective N-methyl-D-aspartate receptor (NMDAR) antagonist, has therapeutic effects within hours in people suffering from depression suggests that modulating glutamatergic neurotransmission is a fundamental step in alleviating the debilitating symptoms of mood disorders. Acutely, ketamine increases extracellular glutamate levels, neuronal excitability, and spontaneous γ oscillations, but it is unknown whether these effects are key to the mechanism of antidepressant action of ketamine.
Methods

Twenty drug-free major depressive disorder patients received a single, open-label intravenous infusion of ketamine hydrochloride (.5 mg/kg). Magnetoencephalographic recordings were made approximately 3 days before and approximately 6.5 hours after the infusion, whereas patients passively received tactile stimulation to the right and left index fingers and also while they rested (eyes-closed). Antidepressant response was assessed by percentage change in Montgomery-Åsberg Depression Rating Scale scores.
Results

Patients with robust improvements in depressive symptoms 230 min after infusion (responders) exhibited increased cortical excitability within this antidepressant response window. Specifically, we found that stimulus-evoked somatosensory cortical responses increase after infusion, relative to pretreatment responses in responders but not in treatment nonresponders. Spontaneous somatosensory cortical γ-band activity during rest did not change within the same timeframe after ketamine in either responders or nonresponders.
Conclusions

These findings suggest NMDAR antagonism does not lead directly to increased cortical excitability hours later and thus might not be sufficient for therapeutic effects of ketamine to take hold. Rather, increased cortical excitability as depressive symptoms improve is consistent with the hypothesis that enhanced non-NMDAR-mediated glutamatergic neurotransmission via synaptic potentiation is central to the antidepressant effect of ketamine.

 

[Kittycat5]

It means the the blockade of NMDA receptor, the most commonly stated mechanism of action of ketamine may not be the reason behind its efficacy in depression. Rather something else effecting the neurotransmission of glutamate (the excitatory neurotransmitter that is the endogenous one for NMDAR), may be the reason.

 

[PaulyF]

OK. Thanks! I'm still wondering how to produce "non-mediated glutamatergic neurotransmisssion via synaptic potentiation". What does that mean?

 

[Solipsis]

Correct me if I'm wrong, but I think this would be relevant reading about LTP: https://en.wikipedia.org/wiki/Long-term_potentiation

also:

Indeed, an enhanced glutamatergic activity transduced through AMPA receptors rather than NMDA receptors may be responsible for mediating the increased synaptic potentiation and activation of early neuroplastic genes observed upon exposure to the drug15 (described below in further detail). Of note, treatment with NBQX, an AMPA receptor antagonist, has been shown to inhibit the antidepressant effects of ketamine in animal models of depression.22, 23 Both AMPA and NMDA receptors are important in long-term potentiation and long-term depression, the two main neurobiological mechanisms which are responsible for mediating activity-dependent synaptic plasticity and re-modeling. Long-term potentiation has primarily been shown to induce dendritic spine growth, and enlargement of pre-existing spines and of the associated post-synaptic density proteins,24 all of which are observed upon ketamine exposure.25 Additionally, ketamine inhibits spontaneous NMDA mini-excitatory post-synaptic currents caused by spontaneous glutamate release at rest.26 Interestingly, brain post mortem studies have described increased glutamate levels in individuals with mood disorders,27 while decreased hippocampal NMDA receptors have been described in bipolar patients.28

http://www.nature.com/mp/journal/v18/n12/full/mp201387a.html

So LTP is about chronically changing the way signals are transduced via a synaptic cleft between neurons, and ketamine apparently influences this via changes in AMPA (and NMDA), leading to the benefits described above. It would change the way glutamate acts as messenger in the synapse, not sure if synaptic levels change or just sensitivity to the glutamate... but in any case it's implicated in change of mood.

I might be off