Nervous system signaling & synaptic transmission
The nervous system couples electrical excitation to chemical synapses: action potentials trigger presynaptic Ca²⁺ influx, SNARE-driven vesicle fusion, and neurotransmitter release; postsynaptic integration uses ionotropic and metabotropic receptors, scaffolds, and kinase networks, with crosstalk to glial metabolic support, neurotrophins, and developmental Notch/Wnt programs. Disease and pharmacology contexts require splice isoforms, subunit composition, and regional expression.
1. Key targets
Core nodes
- Presynaptic release machinery
SNAREs (SNAP25, VAMP, syntaxins); synaptotagmins and SV2/synaptophysin gate Ca²⁺-triggered vesicle cycling.
- Postsynaptic receptors & scaffolds
NMDA/AMPA iGluRs, GABA-A, mGluRs; PSD-95 (DLG4), Shank, Homer organize signaling hubs.
- Plasticity & trophic signaling
BDNF–TrkB, CAMK–CREB, MAPK/PI3K–mTOR and IEGs couple to LTP/LTD programs.
Ion channels & excitability
- Voltage-gated Na⁺/K⁺/Ca²⁺ channels set firing and presynaptic Ca²⁺ entry
- Ligand-gated channels mediate fast excitation/inhibition
Glia & microenvironment
- Astrocytes: glutamate uptake, K⁺ buffering, metabolic support
- Oligodendrocytes/myelin (MBP, PLP1) shape conduction and plasticity
Supplement: nervous system–related targets (gene symbols)
Below the overview, HGNC symbols group neuronal/glia markers, presynaptic vesicle cycling and postsynaptic scaffolds, voltage- and ligand-gated channels, monoaminergic/cholinergic and metabotropic receptors, neurotrophic/developmental crosstalk, and Ca²⁺–kinase–transcription plasticity nodes. Validate splice isoforms, complex subunits, and regional expression with databases and papers.
Neurons & glia
Neuronal structure & markers
MAP2, MAP1B, MAP1A, TUBB3, TUBA1A, NEFH, NEFL, NEFM, RBFOX3, DCX, DCLK1, ENO2, STMN2, SNAP25
Glia & myelin
GFAP, S100B, AQP4, OLIG1, OLIG2, SOX10, CSPG4, MBP, PLP1, MAG, MOG, CNP
Pre- / postsynaptic machinery
Presynaptic release & vesicle cycling
SYT1, SYT2, SYT3, SV2A, SV2B, SV2C, SYP, VAMP1, VAMP2, VAMP3, STX1A, STX1B, STXBP1, SNAP25, SNAP29, NSF, ATP6V1A, ATP6V0A1
Postsynaptic scaffold & signaling complexes
DLG4, DLG1, DLG2, DLG3, SHANK1, SHANK2, SHANK3, HOMER1, HOMER2, HOMER3, GRIP1, GRIP2, NLGN1, NLGN2, NLGN3, NRXN1, NRXN2, NRXN3
Ion channels (representative)
Voltage-gated Na/K/Ca channels (representative)
SCN1A, SCN2A, SCN3A, SCN8A, SCN9A, SCN10A, KCNQ1, KCNQ2, KCNQ3, KCNA1, KCNC1, KCNH2, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, CACNA1I
Ligand-gated ionotropic receptors
GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRIA1, GRIA2, GRIA3, GRIA4, GRID1, GRID2, GABRA1, GABRA2, GABRB1, GABRB2, GABRG2, GABRD, GABRE
Neurotransmitter receptors (representative)
GPCRs: monoaminergic & cholinergic (representative)
DRD1, DRD2, DRD3, DRD4, DRD5, HTR1A, HTR1B, HTR2A, HTR2C, HTR6, HTR7, ADRA1A, ADRA1B, ADRA2A, ADRB1, ADRB2, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5
Neuropeptide & metabotropic glutamate (representative)
OPRM1, OPRK1, OPRD1, OPRL1, NPY, NPY1R, NPY2R, TACR1, MC4R, GRM1, GRM2, GRM3, GRM4, GRM5, GRM6, GRM7, GRM8
Neurotrophic & developmental crosstalk
Neurotrophins & receptor tyrosine kinases
BDNF, NGF, NTF3, NTF4, NTRK1, NTRK2, NTRK3, NGFR, EGF, EGFR, ERBB2, ERBB3, ERBB4, MET, HGF
Axon guidance & developmental crosstalk
ROBO1, ROBO2, SLIT1, SLIT2, NTN1, DCC, UNC5A, UNC5B, NOTCH1, NOTCH2, NOTCH3, DLL1, JAG1, WNT3A, WNT5A, FZD3, FZD7
Plasticity-associated signaling
Ca²⁺ / CAMK–CREB & immediate early genes
CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, PPP3CA, PPP3CB, PPP3R1, CREB1, ATF4, CRTC1, ARC, FOS, JUN, EGR1, NPAS4
MAPK / PI3K–Akt & mTOR (plasticity crosstalk)
MAPK1, MAPK3, MAP2K1, MAP2K2, MAP3K1, PIK3CA, PIK3CB, AKT1, AKT2, MTOR, RPTOR, RICTOR, TSC1, TSC2, RPS6KB1
2. Suggested experimental readouts
For synaptic proteins, pair with totals and subcellular fractions; for phospho sites, follow clone datasheets with stimulation controls.
- Presynaptic/postsynaptic markers: SYP, DLG4, SLC17A7 (vGlut1), GAD2 (GAD65), etc.
- p-CAMKII, p-ERK1/2, p-CREB (e.g., Ser133 per clone) and IEGs such as c-Fos
- Electrophysiology: AMPA/NMDA ratios, PPF—model-dependent
- Glia: GFAP, Iba1 (AIF1), OLIG2 / MBP—tissue/culture dependent
3. E/I balance vs major transmitter systems
| System (examples) | Principal receptor classes | Typical roles | Notes |
|---|---|---|---|
| Glutamate | iGluR (AMPA/NMDA/Kainate), mGluR1–8 | Excitation, plasticity, excitotoxic risk | NMDARs need glycine/D-serine co-agonists and voltage-dependent Mg²⁺ block relief. |
| GABA | GABA-A (pentameric), GABA-B | Fast/slow inhibition, network oscillations | Subunit composition sets pharmacology and developmental expression. |
| Monoamines / ACh | GPCRs, nAChR (pentameric) | Neuromodulation, attention, reward circuits | Extensive crosstalk with second messengers and kinases. |
4. Disease & model context
- Epilepsy & channelopathies: Na⁺/K⁺ channel variants shift excitability; separate acute vs chronic phases in models.
- Neurodegeneration & proteostasis: Synapse loss can precede somatic pathology—pair with behavior and gliosis.
- Psychiatric disorders & circuits: Monoamine and glutamate–GABA E/I hypotheses are widespread—mind species/region differences.
Nervous system–related antibodies (curated)
5. Product lines & on-site search
Primary & phospho antibodies
MAP2, NeuN (RBFOX3), GFAP, SYP, PSD-95, vGlut, GAD, channel subunits, p-CAMKII, p-ERK, p-CREB—WB/IHC/IF/FC as applicable.
Recombinant proteins / cytokines
BDNF, NGF, NT-3 for neuronal survival/plasticity assays—follow datasheets and ethics.
Functional reagents & tools
Receptor antagonists, channel blockers, Ca²⁺ indicators—research use; follow safety/regulations.
6. Inhibitors & tool compounds (summary)
For research use; follow SOP, datasheets, and ethics. Some agents are highly toxic or regulated—compliant labs only.
Competitive NMDAR antagonist; common in LTP/excitotoxicity studies.
AMPA/kainate blockers; dissect glutamatergic excitation.
Block GABA-A–mediated inhibition (toxicity/regulatory caution).
Naᵥ blocker; extremely toxic—strict handling.
CAMKII tool inhibitors—check isoforms/off-targets.
mTORC1/broader mTOR probes; plasticity–autophagy readouts.
7. Pathway schematic
- Action potential → presynaptic Ca²⁺ influx
- SNARE-driven fusion and release
- Receptors/scaffolds recruit kinases/transcription
- Glia & neurotrophins provide metabolic/modulatory input
8. Pathway biology overview
Nervous system function depends on precise timing across distributed circuits—from molecules (channels, transporters, scaffolds) to neuron–glia coupling and network oscillations. Genetic and pharmacological tools should match isoforms and spatiotemporal resolution.
- Development: axon guidance, synaptogenesis/pruning intersect Notch/Wnt/neurotrophin axes
- Homeostatic plasticity: synaptic scaling, mGluR-linked translation-dependent processes
9. Related pathways on this site
10. External databases & modification resources
- KEGG: hsa04080 Neuroactive ligand–receptor interaction
- Reactome: Neuronal System
- WikiPathways (search: nervous system)
- PhosphoSitePlus (receptor/scaffold modification sites)
11. References
Synaptic transmission & plasticity
- • Südhof TC. (2018). Nature. 555(7697):406-415.
- • Nicoll RA, Roche KW. (2013). Science. 342(6158):80-86.
Neurotrophins & disease mechanisms
- • Park H, Poo MM. (2013). Nature. 503(7474):45-51.
- • Holt CE, Schuman EM. (2013). Science. 339(6116):1232-1236.