Fig. 2.

Fear extinction circuitry.

Hypothetical model for the existence of CB1Rs in the known fear and extinction circuits. Connectivity from infralimbic (IL) subregion of the prefrontal cortex to the basolateral amygdala (BLA) is enhanced (extinction promoting glutamatergic neuron shown in green) with extinction training. Activation of prelimbic (PL) subregion of the prefrontal cortex to IL connection (extinction promoting glutamatergic neuron shown in green) increases fear extinction. Connectivity from BLA to the PL is enhanced (fear promoting glutamatergic neuron shown in red) with fear learning under the control of local parvalbumin interneurons (PV⁺ IN) (shown in blue) in PL. Extinction training increases perisomatic connections of the local BLA interneurons (PV⁺ IN) to the fear neurons. Extinction training increases perisomatic connections of CCK⁺ interneurons (shown in orange) to fear neurons thus CB1R mediated inhibition of GABA release to reduce fear. The ventral subunit of hippocampus (vHC) connections to BLA increases fear (fear promoting glutamatergic neuron shown in red). vHC connections to PL (fear reducing glutamatergic neuron shown in black) decreases fear. vHC connections to IL (fear promoting glutamatergic neuron shown in red) increases fear and innervations onto local PV⁺INs in IL control the feed forward inhibition thus the relapse of fear after extinction (renewal).