Impaired glutamate reuptake induces synaptic mistuning in rat hippocampal slices, that can be counteracted by ketamine
Erika Vazquez Juarez, Ipsit Srivastava, Maria Lindskog
bioRxiv Preprint Server January 25, 2022 preprint DOI: 10.1101/2022.01.25.477658 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Rat hippocampal slices and a rat model of depression |
| Interventions | DL-TBOA ketamine |
| Topics | Ketamine Neuroplasticity Esketamine |
| Keywords | Psychiatric disorders Mental health Neurological disorders Brain disorders Neuropsychiatric conditions Neurotransmission Synaptic function Brain signals Neural communication Long-term potentiation Glutamate Antidepressant Therapeutic Drug treatment Psychiatric medication Brain circuits Neural networks Brain function Circuit rebalancing Neural circuits |
| Citations | 1 |
| Key findings | Ketamine counteracts the effects of increased glutamate on synaptic retuning, suggesting its antidepressant mechanism is restoring adequate synaptic tuning. |
Abstract
Mistuning of synaptic transmission has been proposed to underlie many psychiatric disorders, with decreased reuptake of the excitatory neurotransmitter glutamate as one contributing factor. Synaptic tuning occurs through several diverging and converging forms of plasticity. By recording evoked field postsynaptic potentials in the CA1 area in hippocampal slices, we found that inhibiting glutamate transporters using DL-TBOA causes retuning of synaptic transmission, resulting in a new steady state with reduced synaptic strength and a lower threshold for inducing long-term synaptic potentiation (LTP). Moreover, we also found reduced threshold for LTP in a rat model of depression that has decreased levels of glutamate transporters. Most importantly, we found that the antidepressant ketamine counteracts the effects of increased glutamate on the various steps involved in synaptic retuning. We therefore propose that ketamine’s mechanism of action as an antidepressant is to restore adequate synaptic tuning.