Lateral, not medial, prefrontal cortex contributes to punishment and aversive instrumental learning

Abstract

Aversive outcomes punish behaviors that cause their occurrence. The prefrontal cortex (PFC) has been implicated in punishment learning and behavior, although the exact roles for different PFC regions in instrumental aversive learning and decision-making remain poorly understood. Here, we assessed the role of the orbitofrontal (OFC), rostral agranular insular (RAIC), prelimbic (PL), and infralimbic (IL) cortex in instrumental aversive learning and decision-making. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused mild punishment (punished lever) but continued pressing the other lever that did not cause punishment (unpunished lever). Inactivations of OFC, RAIC, IL, or PL via the GABA agonists baclofen and muscimol (BM) had no effect on the acquisition of instrumental learning. OFC inactivations increased responding on the punished lever during expression of well-learned instrumental aversive learning, whereas RAIC inactivations increased responding on the punished lever when both levers were presented simultaneously in an unpunished choice test. There were few effects of medial PFC (PL and IL) inactivation. These results suggest that lateral PFC, notably OFC and RAIC, have complementary functions in aversive instrumental learning and decision-making; OFC is important for using established aversive instrumental memories to guide behavior away from actions that cause punishment, whereas RAIC is important for aversive decision-making under conditions of choice.

Figure 1.

Effects of orbitofrontal cortex (OFC) inactivations. (A) OFC cannula placements as verified by Nissl-stained sections. Black dots represent the ventral point of the cannula tract, indicated on coronal sections adapted from Paxinos and Watson (2007). (B) Mean ± SEM lever-presses on the punished and unpunished levers during the last day of lever-press training (T) and punishment acquisition (sessions 1–5). Arrows indicate days that rats received infusions of either saline (n = 6) or baclofen and muscimol (BM) (n = 9) immediately prior to the session. (C) Mean ± SEM latency to initially press the punished and unpunished lever (averaged across trials) during punishment acquisition. (D) Mean ± SEM lever-press ratios of BM on lever pressing during punishment expression (n = 15). (E) Mean ± SEM latency to initially press the punished and unpunished lever (averaged across trials) during punishment expression after infusions of saline or BM. (F) Mean ± SEM magazine entries during punishment expression after infusions of saline or BM. (G) Mean ± SEM lever–press ratios of BM on lever pressing during aversive choice (n = 15). (H) Mean ± SEM latency to initially press the punished and unpunished levers during choice test after infusions of saline or BM. (I) Mean ± SEM magazine entries during choice test after infusions of saline or BM. (*) P < 0.05.

Figure 2.

Effects of insular cortex (RAIC) inactivations. (A) RAIC cannula placements as verified by Nissl-stained sections. Black dots represent the ventral point of the cannula tract, indicated on coronal sections adapted from Paxinos and Watson (2007). (B) Mean ± SEM lever-presses on the punished and unpunished levers during the last day of lever-press training (T) and punishment acquisition (sessions 1–5). Arrows indicate days that rats received infusions of either saline (n = 7) or baclofen and muscimol (BM) (n = 7) immediately prior to the session. (C) Mean ± SEM latency to initially press the punished and unpunished levers (averaged across trials) during punishment acquisition. (D) Mean ± SEM lever-press ratios of BM on lever pressing during punishment expression (n = 15). (E) Mean ± SEM latency to initially press the punished and unpunished levers (averaged across trials) during punishment expression after infusions of saline or BM. (F) Mean ± SEM magazine entries during punishment expression after infusions of saline or BM. (G) Mean ± SEM lever-press ratios of BM on lever pressing during aversive choice (n = 15). (H) Mean ± SEM latency to initially press the punished and unpunished levers during choice test after infusions of saline or BM. (I) Mean ± SEM magazine entries during choice test after infusions of saline or BM. (*) P < 0.05.

Figure 3.

Effects of prelimbic cortex (PL) inactivations. (A) PL cannula placements as verified by Nissl-stained sections. Black dots represent the ventral point of the cannula tract, indicated on coronal sections adapted from Paxinos and Watson (2007). (B) Mean ± SEM lever-presses on the punished and unpunished levers during the last day of lever-press training (T) and punishment acquisition (sessions 1–5). Arrows indicate days that rats received infusions of either saline (n = 7) or baclofen and muscimol (BM) (n = 8) immediately prior to the session. (C) Mean ± SEM latency to initially press the punished and unpunished levers (averaged across trials) during punishment acquisition. (D) Mean ± SEM lever-press ratios of BM on lever pressing during punishment expression (n = 15). (E) Mean ± SEM latency to initially press the punished and unpunished lever (averaged across trials) during punishment expression after infusions of saline or BM. (F) Mean ± SEM magazine entries during punishment expression after infusions of saline or BM. (G) Mean ± SEM lever-press ratios of BM on lever pressing during aversive choice (n = 15). (H) Mean ± SEM latency to initially press the punished and unpunished levers during choice test after infusions of saline or BM. (I) Mean ± SEM magazine entries during choice test after infusions of saline or BM.

Figure 4.

Effects of infralimbic cortex (IL) inactivations. (A) IL cannula placements as verified by Nissl-stained sections. Black dots represent the ventral point of the cannula tract, indicated on coronal sections adapted from Paxinos and Watson 2007. (B) Mean ± SEM lever-presses on the punished and unpunished levers during the last day of lever-press training (T) and punishment acquisition (sessions 1–5). Arrows indicate days that rats received infusions of either saline (n = 7) or baclofen and muscimol (BM) (n = 11) immediately prior to the session. (C) Mean ± SEM latency to initially press the punished and unpunished levers (averaged across trials) during punishment acquisition. (D) Mean ± SEM lever-press ratios of BM on lever pressing during punishment expression (n = 18). (E) Mean ± SEM latency to initially press the punished and unpunished levers (averaged across trials) during punishment expression after infusions of saline or BM. (F) Mean ± SEM magazine entries during punishment expression after infusions of saline or BM. (G) Mean ± SEM lever-press ratios of BM on lever pressing during aversive choice (n = 18). (H) Mean ± SEM latency to initially press the punished and unpunished levers during choice test after infusions of saline or BM. (I) Mean ± SEM magazine entries during choice test after infusions of saline or BM. (*) P < 0.05.