Uncertainty-Dependent Extinction of Fear Memory in an Amygdala-mPFC Neural Circuit Model
Fig 1
Partial reinforcement effect and the neural circuit models.
(A, B) During fear conditioning, a CS, e.g., a tone, was fully (in the full reinforcement schedule (A)) or partially (in the partial reinforcement schedule (B)) paired several times with a US, e.g., electric foot shock (left panels). The fear memory formed during fear conditioning can be diminished by extinction training, during which the CS is repeatedly presented alone, without the US (right panels). (C) Conditioned responses to the CS, which are usually measured as the degree of behavioral freezing responses, are depicted during fear conditioning and extinction. The fear memory (measured as the degree of behavioral freezing responses) that was acquired through the partial reinforcement schedule with P(US|CS)<1 exhibits a PREE (blue line), which is evident as increased resistance to extinction compared to that of the fear memory acquired through the full reinforcement schedule with P(US|CS) = 1 (black line). (D, E) The two neural circuit models are shown as schematics. Black and blue lines describe synaptic connections and the learning signals that regulate plasticity at synapses indicated by black open circles, respectively. (D) The basic model based on fear, persistent and extinction neural units (F, P and E). CS-related input activates all the units, and the extinction neural unit inhibits the fear neural unit, the activity of which represents the strength of the fear memory (black lines) (eqs (1–3)). The efficacy of CS-related input to the fear, persistent and extinction neural units changes based on the learning signals (blue lines) (eqs (4–6)). (E) Extended model including subregions of the amygdala (the LA, CEA and ITC) as well as the vmPFC. In this model, the LA and CEA correspond to persistent and fear neural units, respectively, and there are two extinction neural units: the ITC and vmPFC. CS-related input activates all subregions, and the ITC receives excitatory input from the vmPFC and inhibits the CEA (black lines) (eqs (7–10)). A behavioral fear response was triggered by the CEA. The efficacy of plastic synapses (black open circles) changed based on learning signals (blue lines) (eqs (11–14)). Parameter values are listed in S1 Table.