Medial prefrontal cortex circuit function during retrieval and extinction of associative learning under anesthesia

Abstract

Associative learning is encoded under anesthesia and involves the medial prefrontal cortex (mPFC). Neuronal activity in mPFC increases in response to a conditioned stimulus (CS+) previously paired with an unconditioned stimulus (US) but not during presentation of an unpaired stimulus (CS-) in anesthetized animals. Studies in conscious animals have shown dissociable roles for different mPFC subregions in mediating various memory processes, with the prelimbic (PL) and infralimbic (IL) cortex involved in the retrieval and extinction of conditioned responding, respectively. Therefore PL and IL may also play different roles in mediating the retrieval and extinction of discrimination learning under anesthesia. Here we used in vivo electrophysiology to examine unit and local field potential (LFP) activity in PL and IL before and after auditory discrimination learning and during later retrieval and extinction testing in anesthetized rats. Animals received repeated presentations of two distinct sounds, one of which was paired with footshock (US). In separate control experiments animals received footshocks without sounds. After discrimination learning the paired (CS+) and unpaired (CS-) sounds were repeatedly presented alone. We found increased unit firing and LFP power in PL and, to a lesser extent, IL after discrimination learning but not after footshocks alone. After discrimination learning, unit firing and LFP power increased in PL and IL in response to presentation of the first CS+, compared to the first CS-. However, PL and IL activity increased during the last CS- presentation, such that activity during presentation of the last CS+ and CS- did not differ. These results confirm previous findings and extend them by showing that increased PL and IL activity result from encoding of the CS+/US association rather than US presentation. They also suggest that extinction may occur under anesthesia and might be represented at the neural level in PL and IL.

Neural Oscillatory Correlates for Conditioning and Extinction of Fear

“…Due to their physical proximity and similar input, it was surprising that LFPs were drastically different between the two regions. Interestingly, such theta power effect was not seen in female mice as they displayed heightened freezing and persistently increased mPFC theta in both PL and IL [ 39 ].…”

An Emergent Discriminative Learning Is Elicited During Multifrequency Testing

“…Previous studies have demonstrated the involvement of the mPFC in the regulation of conditioned fear learning (Resstel et al, 2006; Almada et al, 2013; Marek et al, 2018; Spalding, 2018). Although mPFC neurons respond to noise (Bubser and Koch, 1994; Kim et al, 2009; Likhtik et al, 2014), clicks (Mihalick et al, 2001; Martin-Cortecero and Nunez, 2016; Janetsian-Fritz et al, 2018) and pure tones (Sierra-Mercado et al, 2006; Fenton et al, 2014; Likhtik et al, 2014), iso-frequency pure tones such as 3 kHz (Fenton et al, 2014), 4 kHz (Sierra-Mercado et al, 2006), and 8 kHz (Likhtik et al, 2014) have been used as CSs in conditioned fear learning. Since there has been no further study on the frequency response properties of mPFC neurons to pure tones, the pure tone responses of mPFC neurons and whether they change after auditory fear conditioning, as well as the connection between the sound responses of mPFC neurons and any hypothetical emergent discriminative learning, remain unclear.…”

Odor Modulates the Temporal Dynamics of Fear Memory Consolidation

“…In rodent studies, the PL has been implicated in the expression and renewal of fear responses (Corcoran and Quirk, 2007;Sierra-Mercado et al, 2011;Orsini and Maren, 2012;Courtin et al, 2014;Fenton et al, 2014;Corches et al, 2019) and increased activity in this region is associated with extinction deficits (Burgos-Robles et al, 2009) as well as increased input to the basolateral amygdala (BLA) (Likhtik et al, 2005;Maren et al, 2013), an output which promotes freezing behavior and fear (Vidal- Gonzalez et al, 2006).…”