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. 2018 Feb 12;145(2):111–124. doi: 10.1111/jnc.14290

Figure 6.

Figure 6

Illustrative diagram showing putative mechanisms underlying the effects of NMDA receptor antagonism and allosteric mGluR5 modulation on glutamate efflux in the mPFC. (a) NMDA receptor antagonism inhibits GABA‐ergic neurons leading to a disinhibition of glutamatergic neurons and increased glutamate efflux. (b) Positive allosteric mGluR5 modulation activates GABA‐ergic neurons and glutamatergic neurons via the activation of pre‐ and post‐synaptic mGluR5 resulting in increased glutamate efflux. (c) NMDA receptor antagonism and positive allosteric mGluR5 modulation leads to a reversal of (i) NMDA receptor antagonist‐induced disinhibition; (ii) post‐synaptic mGluR5 activation of glutamatergic neurons; (iii) pre‐synaptic mGluR5 autoreceptor activation, leading to increased glutamate efflux. (d) Negative allosteric mGluR5 modulation inhibits GABA‐ergic neurons and glutamatergic neurons leading to decreased glutamate efflux. This is a hypothesized proposal since we did not assess GABA‐ergic mechanisms.