Basically, when the synaptic transmission between the hippocampus and the prefrontal cortex is disrupted, symptoms of mental illnesses such as schizophrenia are seen. This has been known for a long time. What wasn’t known was how is this communication between the hippocampus and prefrontal cortex disrupted? That is, what are the mechanisms responsible for the disruption of communication between these two regions of the brain? Well, in this paper below, they show over activation of the D2-like Dopamine receptors leads to a decrease in another type of receptor called the NMDA receptor. This leads to a marked disruption of synaptic transmission between the two brain regions. This newly discovered relationship between the Dopamine and NMDA receptors may lead to treatment options for people with mental illnesses like schizophrenia.
“Synaptic transmission between the hippocampus and prefrontal cortex is required for many executive cognitive functions. It is believed that disruption of this communication contributes to symptoms observed in psychiatric disorders including schizophrenia. Hyperdopaminergic tone and hypofunction of NMDA receptor-mediated glutamate transmission are distinctive elements of schizophrenia. Here we demonstrate that activation of low-affinity D2-like dopamine receptors leads to a lasting depression of NMDA receptors at the hippocampal– prefrontal projection of juvenile rats, leading to a marked disruption of synaptic transmission. These data demonstrate a link between dopamine and hypofunction of NMDA receptormediated transmission with potential implications for psychiatric disease.”
“New research has identified the mechanisms that trigger disruption in the brain’s communication channels linked to symptoms in psychiatric disorders including schizophrenia. The University of Bristol study, published in the Proceedings of National Academy of Sciences, could have important implications for treating symptoms of brain disorders.
Many of our everyday cognitive functions such as learning and memory rely on normal communication between the two regions of the brain – the hippocampus and prefrontal cortex. While previous studies have identified disruption to communication channels in these two areas of the brain contribute to symptoms in psychiatric disorders, the mechanisms that lead to these disturbances have been largely unknown, until now.
In this study, led by Professor Zafar Bashir from Bristol’s School of Physiology and Pharmacology, the researchers studied the neurotransmitters glutamate and dopamine, which work together in controlling normal transmission between these brain regions by communicating chemical information throughout our brain and are disrupted in schizophrenics.
The team found that subtle changes in the interplay of these transmitters completely altered the flow of information from the hippocampus to prefrontal cortex. Over-activation of the D2 class of dopamine receptors led to suppression of the function of NMDA receptors, which are activated by the neurotransmitter glutamate, at the synaptic connection between hippocampus and prefrontal cortex. This in turn leads to a marked disruption of communication between these brain regions.
Dr Paul Banks, one of the researchers, said: “Our findings demonstrate a mechanism for how dopamine neurotransmission can influence NMDA receptor function at a connection in the brain needed for complex mental tasks which are disrupted in schizophrenic patients. It has been known for some time that dopamine and NMDA receptor function are altered in schizophrenic patients – our data mirror the direction of these changes and therefore might give insight into how these changes come about mechanistically.”