Ketamine and consciousness
NMDA receptors play multiple roles in cortical synapses. Its main role is its contribution to synaptic plasticity, including LTP and long-term depression (LTD) (Bliss et al. , 2016). Depending on the stimulation pattern and postsynaptic depolarisation, activation of the NMDA receptor may lead to LTP and LTD in the cingulate cortex. Postsynaptic AMPA receptors, including different subtypes of receptors-mediate synaptic potentiation and depression (Bliss et al. , 2016). In addition, there are reports of silent or pure NMDA receptors in the adult cortex (Zhuo, 2023). In physiological awake conditions, these NMDA receptors may contribute to synaptic transmission. Ketamine is an old anesthetic agent that acts as a non-competitive NMDA receptor antagonist. It is reported that ketamine-induced anesthesia is accompanied by the development of slow oscillation across the cortex (Ballesteros et al. , 2020).
In healthy human subjects, low-dose of ketamine can produce altered states of consciousness (Vlisides et al. , 2018), suggesting that NMDA receptor functions play important roles in controlling consciousness under physiological conditions. Considering that most of NMDA receptors are inhibited at resting membrane potentials, these results suggest that the ketamine effect may be mediated by non-activity-dependent synaptic plasticity mechanisms, such as functional NMDA receptors and/or presynaptic NMDA receptors.