Table 5.
Microcircuit alterations in the VPA rat model of autism.
| Measurement | Region | Effect | Dose (mg/kg) | ED VPA admin | PND testing | Reference |
|---|---|---|---|---|---|---|
| Single-neuron patch clamp | ||||||
| NMDAR current influx | S1 | Enhanced | 500 | 12.5 | 12–16 | Rinaldi et al., 2007b |
| AMPAR current influx | S1 | No effect | 500 | 12.5 | 12–16 | Rinaldi et al., 2007b |
| AMPA/NMDA current influx ratio | S1 | Decreased | 500 | 12.5 | 12–16 | Rinaldi et al., 2007b |
| AP evoked calcium transients | S1 | No effect | 500 | 12.5 | 12–16 | Rinaldi et al., 2007b |
| Multi-neuron patch clamp | ||||||
| Direct and disynaptic connectivity between layer 5 pyramidal neurons less than 50 μm apart | S1 | Enhanced by more than 50% | 500 | 12.5 | 12–16 | Rinaldi et al., 2007a |
| Direct and disynaptic connectivity between layer 5 pyramidal neurons 100–200 μm apart | S1 | No effect | 500 | 12.5 | 12–16 | Rinaldi et al., 2007a |
| Strength of direct connections between layer 5 pyramidal neurons | S1 | Decreased | 500 | 12.5 | 12–16 | Rinaldi et al., 2007a |
| Electrical excitability of layer 2/3 and 5 neurons | S1 | Decreased | 500 | 12.5 | 12–16 | Rinaldi et al., 2007a |
| AP amplitude, threshold, input resistance | S1 | No effect | 500 | 12.5 | 12–16 | Rinaldi et al., 2007a |
| Network reactivity measured with MEA | ||||||
| Network reactivity to excitatory inputs in layer 2/3 and layer 5 (voltage clamp at GABAA reversal potential ∼ −57 mV) | S1 | Enhanced | 500 | 12.5 | 12–16 | Rinaldi et al., 2007a |
| Network reactivity to inhibitory inputs in layer 2/3 and layer 5 (voltage clamp at AMPA reversal potential ∼+10 mV) | S1 | Enhanced | 500 | 12.5 | 12–16 | Rinaldi et al., 2007a |
| Network excitatory/inhibitory balance | S1 | No effect | 500 | 12.5 | 12–16 | Rinaldi et al., 2007a |
| Network reactivity to excitatory inputs (voltage clamp at GABAA reversal potential ∼−57 mV) | LA | Enhanced | 500 | 12.5 | 12–16 | Markram et al., 2007 |
| Network reactivity to inhibitory inputs (voltage clamp at AMPA reversal potential ∼+10 mV) | LA | Decreased | 500 | 12.5 | 12–16 | Markram et al., 2007 |
| Reverberant activity | LA | Enhanced | 500 | 12.5 | 12–16 | Markram et al., 2007 |
| Synaptic plasticity | ||||||
| Postsynaptic LTP | S1 | Enhanced | 500 | 12.5 | 12–16 | Rinaldi et al., 2007b |
| Postsynaptic LTP | LA | Enhanced | 500 | 12.5 | 12–16 | Markram et al., 2007 |
Results describe the VPA-treated offspring group relative to controls. All studies were performed on male rats. Abbreviations: AP, action potential; ED, embryonic day; LA, lateral nucleus of the amygdala; LTP, long-term potential; M, male; S1, primary somatosensory cortex; VPA, valproic acid.