Comparison of the significancea of several functionalities related with the synaptic activity across the three groups analyzed (Younger, Elder, and MCI)
| Functionality | Younger | Elder | MCI |
|---|---|---|---|
| Synaptic signaling | 23.66 | 13.48 | 10.66 |
| Synaptic plasticity regulation | 12.58 | 13.28 | 5.45 |
| Synaptic organization | 12.77 | 4.51 | 2.70 |
| Cellular response to serotonin | 3.06 | 2.30 | 0 |
| Cellular response to catecholamines | 6.02 | 0 | 0 |
| Cellular response to epinephrine | 3.36 | 0 | 0 |
| Cellular response to dopamine | 3.14 | 0 | 0 |
| Cellular response to glycine | 2.90 | 0 | 0 |
| GABAergic signaling | 2.51 | 0b | 1.57 |
| GAP junctions (electrical synapses) | 4.31 | 0 | 4.44 |
| Glutamatergic synaptic transmissionc | 11.35 | 7.24 | 3.19 |
| Glutamatergic synaptic transmissiond | 18.57 | 5.43 | 11.88 |
| Glutamate secretion | 2.35 | 3.19 | 1.59 |
| NMDAR activation & post-synaptic events | 8.30 | 6.60 | 4.00 |
| Regulation of NMDAR activation | 2.54 | 2.04 | 6.05 |
| Retrograde endocannabinoids signaling | 1.31 | 1.79 | 5.51 |
| CA1-Schaffer collateral synapses | 2.62 | 1.84 | 3.45 |
| Somato-dendritic compartment | 28.41 | 12.31 | 8.62 |
| Dendrites | 23.22 | 9.86 | 8.45 |
| G protein-coupled glutamate receptors | 1.88 | 0 | 2.36 |
| G protein-coupled receptors | 4.31 | 1.51 | 1.93 |
| BDNF signaling | 10.76 | 9.14 | 2.44 |
| CREB1 activation by NMDAR/RAS | 1.32 | 0 | 0 |
| CREB1 activation by PKA | 0 | 1.32 | 0 |
| CREB1 activation by CAMKIV | 0 | 1.32 | 0 |
| MAPK cascade | 6.95 | 3.23 | 2.57 |
| Trafficking AMPAR | 2.27 | 1.79 | 1.81 |
| Membrane lipid rafts | 8.47 | 3.34 | 0 |
| Response to mechanical stimulus | 9.00 | 5.81 | 1.45 |
| Long-term synaptic potentiation (LTP) | 6.22 | 5.83 | 6.32 |
| Long-term synaptic depression (LTD) | 3.16 | 4.24 | 11.43 |
| LTP: LTD ratio | 1.96 | 1.37 | 0.55 |
a The significance is quantified as –log10 (FDR), where FDR is the false discovery rate; b the Elder Group showed a negative regulation of GABAergic signaling (FDR = 4 × 10–2); c based on biological process ontology; d based on cellular component ontology. Note that a zero value denotes a non-significant functionality, as FDR = 1 (For details of the genes involved, see Tables S1–S3)