Table 2.
Roles of PARs (PAR1 and PAR2) in the modulation of neurotransmission and synaptic plasticity.
| Receptor | Neurotransmitter System | Effect | Main Response/Mechanism | Brain Area/Cellular Population | References |
|---|---|---|---|---|---|
| PAR1 | Glutamatergic Transmission |
↑ | Increased NMDAR-mediated spontaneous EPSCs |
Hippocampus CA1 area, Pyramidal neurons |
[56] |
| ↑ | Potentiated NMDA-activated currents and NMDARs-mediated spontaneous EPSCs, due to PAR1-induced glutamate release | Hippocampus CA1 Area, Pyramidal neurons |
[57,58] | ||
| ↑ | NMDAR-dependent LTP of field EPSPs | Hippocampus, CA3-CA1 synapses | [60] | ||
| ↑ | Increased NMDAR-mediated currents and LTP of fEPSPs, due to astrocyte-released glutamate via Best-1 channels | Hippocampus, CA3-CA1 synapses | [59] | ||
| ↑ | Impaired NMDAR-dependent TBS-induced LTP of fEPSPs in PAR1 knockout mice | Hippocampus, CA3-CA1 synapses | [61] | ||
| ↑ | Potentiated NMDAR-mediated spontaneous transmission, due to astrocytic PAR1-induced glutamate release | Nucleus of solitary tract, neurons | [63] | ||
| ↑ | Increased glutamate release, elicited by astrocytic PAR1-released endovanilloids (EVs) and TRPV1 activation | Nucleus of solitary tract, neurons | [64] | ||
| ↑ | Increased spontaneous EPSCs, due to enhanced glutamate release | Spinal cord, Substantia gelatinosa neurons | [65] | ||
| ↓ | Reduced NMDAR-mediated EPSCs and decreased NMDAR-dependent LTP of field EPSPs | Hippocampal CA3-CA1 synapses | [62] | ||
| ↓ | Reduced AMPAR-mediated EPSCs | Hippocampal CA1 area, pyramidal neurons | [62] | ||
| ↓ | LTD of NMDAR-mediated EPSCs, due to PAR1-induced NMDARs endocytosis |
Substantia nigra compacta, DA neurons | [66] | ||
| ↓ | Reduced NMDA-activated currents | Substantia nigra compacta, DA neurons | [66] | ||
| = | Unaffected synaptic and extrasynaptic AMPAR-mediated currents | Substantia nigra compacta, DA neurons | [66] | ||
| ↓ | Reduced mGluR5 expression | Astrocytic cultures | [67] | ||
| PAR1 | GABAergic transmission |
↓ | Reduced spontaneous and evoked IPSCs due to PAR1-dependent eCB-mediated decrease of GABA release | Hippocampal neuronal cultures | [70] |
| PAR2 | Glutamatergic transmission | ↓ | LTD of fEPSPs (NMDAR-mediated) | Hippocampus, CA3-CA1 synapses |
[68] |
| ↓ | LTD of fEPSPs (TRPV4-mediated) | Hippocampus, CA3-CA1 synapses |
[69] | ||
| GABAergic transmission |
↓ | Reduced spontaneous IPSCs | Spinal cord dorsal horn, neurons |
[71] |