GABA interneurons at NMDA receptor-containing synapses (Figure 4-29B and 4-30B). It is also possible that the dysconnectivity of upstream glutamate neurons in the hippocampus contributes to downstream mesolimbic dopamine hyperactivity via a four-neuron circuit (Figure 4-31A). That circuit consists of (1) the dysconnected and defective hippocampal parvalbumin-containing GABA interneuron, going to (2) the hippocampal glutamate neuron projecting to the nucleus accum- bens; then that neuron projecting to two GABA spiny neurons in sequence, (3) the first GABA spiny neuron going from nucleus accumbens to globus pallidus, and finally (4) the second GABA spiny neuron going from globus pallidus to VTA (Figure 4-31A). Loss of adequate glutamate function at parvalbumin-containing GABA interneurons in the hippocampus could lead to hyperactive glutam- ate output from glutamate neurons that project by this circuit to the mesolimbic dopamine neurons in the VTA, with consequential dopamine hyper- activity and positive symptoms of schizophrenia (Figure 4-31B). Stimulating two GABA neurons in sequence has the net effect of disinhibition (inhib- ition of inhibition) at the VTA, the same result as direct stimulation (which was illustrated for the prefrontal cortex in Figure 4-30A). The bottom line is that excessive upstream glutamate output from either the prefrontal cortex or the hippocampus may contribute to downstream dopamine hyper- activity and positive symptoms of schizophrenia. L