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.