G-protein coupled receptors and synaptic plasticity in sleep deprivation

Table 1 Comparative features of long term potentiation and long term depression and their implications in sleep and associated functions

	Prominent brain regions	Receptors involved	Induction	Maintenance	Association with sleep	Functional significance
LTP: Strengthening of synaptic transmission due to a transient high frequency stimulation of the synapses	Cerebellum, hippocampus, cerebral cortex	Ionotropic: NMDARs, AMPARs	Requires activation of both pre- and post-synaptic neurons at the same time for glutamate to fully activate the NMDA receptors [51].	Secondary activation of receptors like AMPARs by glutamate needed for maintenance of LTP[51].	Active nature of LTP likely associated with active state of sleep.	Enhances synaptic response as well as neuronal excitability.
		Metabotropic: Group I mGluRs	Ionotropic induction requires activation of NMDARs by glutamate released from pre-synaptic neurons for higher Ca2+ influx in the post-synaptic neuron [51].	Requires activation of intermediate protein kinases like CaMKIV, protein kinase M-ζ, PKA etc. by high Ca2+ concentration to release membrane obscured AMPARs[56].	More commonly linked with REM sleep associated cellular and molecular modulation of synaptic plasticity[57].	Involved in memory consolidation and learning: Strengthened synapses promote long-term memory storage[58]; Promotes associative and spatial learning[59]; Involved in motor learning and task reperformance[60,61].
			Metabotropic induction works via an increase in intracellular Ca2+ release through mGluR activated phospholipase C and synthesis of secondary messengers IP3 and DAG[54,55].
LTD: Weakening of the synaptic strength due to a relatively low frequency stimulation of the synapses	Cerebellum, hippocampus, cerebral cortex	Ionotropic: NMDARs	Activation of pre-synaptic neuron sufficient to trigger a moderate response of NMDA receptors and does not require both synapses to be activated at the same time[51].	Deactivation of AMPARs involved in maintenance of LTD[131].	Suppressive nature of LTD more likely to be associated with quiescent state of sleep.	Interferes with LTP thereby providing a counteractive balance to prevent hyperexcitability of neurons[52].
		Metabotropic: GPCRs like mGlu1Rs, mGlu5Rs, GABA-B	Ionotropic induction requires moderate activation of NMDA receptors by glutamate for Ca2+ influx in post-synaptic neuron which is lower than that for LTP induction[52].	Requires activation of intermediate protein phosphatases like protein phosphatase 1, 2 and calcineurin by low Ca2+ concentration to inhibit the release of membrane obscured AMPARs[53].	More commonly linked with SWS associated cellular and molecular modulation of synaptic plasticity[64].	Involved in memory consolidation and learning: Weakened state of synapses implicated in forgetting old memories in order to make space for new ones [65]; Involved in novelty acquisition and spatial learning[66].
			Metabotropic induction through mGlu1Rs and mGlu5Rs causes endocytosis of the expressed AMPARs and/or a decrease in phospholipase C via reduced adenylyl cyclase activity[62].
			Enhancement of GABA-B mediated inhibitory effects may result in LTD[63].

GABA-B: Gamma-amino butyric acid-B; NMDA: N-methyl-D-aspartate; SWS: Slow wave sleep; AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; LTP: Long term potentiation; LTD: long term depression; mGlu: Metabotropic glutamate; 5-HT: 5-hydroxytryptamine.