Glutamate Hypothesis of Schizophrenia - 5-HT

5-HT

This deficit in activation also results in a decrease in activity of 5-HT1A receptors in the raphe nucleus.(Bantick, Deakin, Grasby 2001) This serves to increase global serotonin levels, as 5-HT1A serves as an autoreceptor The 5-HT1B receptor, also acting as an autoreceptor, specifically within the striatum, but also parts of basal ganglia then will inhibit serotonin release. This disinhibits frontal dopamine release. The local deficit of 5HT within the striatum, basal ganglia, and prefrontal cortex causes a deficit of excitatory 5-HT6 signalling. This receptor is primarily GABAergic, as such, it causes an excess of glutamatergic, norepinephrinic, dopaminergic, and cholinergic activity within the prefrontal cortex and the striatum. An excess of 5-HT7 signaling within the thalamus also creates too much excitatory transmission to the prefrontal cortex. Combined with another critical abnormality observed in schizoid patients: 5-HT2A dysfunction, this altered signalling cascade creates cortical, thus cognitive abnormalities. 5-HT2A allows a link between cortical, thus conscious, and the basal ganglia,unconscious. Axons from 5-HT2A neurons in layer V of the cerebral cortex reach the basal ganglia, forming a feedback loop, allowing us to condition ourselves. Signalling from layer V of the cerebral cortex to the basal ganglia alters 5-HT2C signalling. This feedback loop with 5-HT2C is how the outer cortex layers can exert some control over our neurochemicals, specifically oxytocin and vasopressin. This alteration in this limbic-layer five axis creates the profound change in social cognition, and sometimes cognition as a whole that is observed in schizoid patients. However, genesis of the actual alterations is a much more complex phenomena.