FIGURE 6.

After passing the blood brain barrier, TNF-α can bind to TNF receptors on neurons resulting in an increased expression of IP3 receptors on the endoplasmic reticulum. LPS binds to TLR4s on neurons and can increase levels of IP3 by increasing PLC mediated cleavage of PIP2 to DAG and IP3. The combination of increased IP3 and IP3 receptors could lead to an excessive release of calcium from the endoplasmic reticulum, with a subsequent large increase in glutamate release into the extracellular space. If GABA synthesis is reduced due to prenatal maternal immune activation reducing expression of GAD, there could be a resultant imbalance of extracellular GABA and glutamate levels. A GABA/glutamate imbalance could lead to unsynchronized and hyperexcitable neuronal firing.