Fig. 1
From: Oxytocin modulates hippocampal perfusion in people at clinical high risk for psychosis
Simplified schematic of proposed neural circuit mechanisms of hippocampal pathophysiology in those at CHR-P. In (1), low glutamate signal/input from hypofunctioning NMDARs (akin to ‘faulty homeostatic sensors’) leads GABAergic interneurons to seek to homeostatically increase excitation by reducing inhibition (disinhibition) of glutamatergic pyramidal cells. However, by disinhibiting pyramidal cells (and thus increasing glutamate signalling) in this dysfunctional neural environment, the potential homeostatic adaptation becomes allostatic (2). In (3), enhanced excitation leads to an overdrive in the responsivity of midbrain dopamine neurons which project to the associative striatum (note that the connection between hippocampal pyramidal cells and midbrain dopamine neurons is presented as monosynaptic but is actually polysynaptic via the ventral striatum and ventral pallidum). Completing the (simplified) circuit, local glutamatergic tone is increased in (4) but is not detected as such by hypofunctioning NMDARs on GABAergic interneurons. For detailed original diagrams and discussion of evidence for this proposed circuit or its component processes, see [7, 11, 12, 14, 74]. Glu glutamate, NMDAR N-methyl-D-aspartate receptor, E/I excitation/inhibition
