D1 receptor modulation of hippocampal-prefrontal cortical circuits integrating spatial memory with executive functions in the rat

Abstract

Dopamine (DA) within the prefrontal cortex (PFC) plays an important role in modulating the short-term retention of information during working memory tasks. In contrast, little is known about the role of DA in modulating other executive aspects of working memory such as the use of short-term memory to guide action. The present study examined the effects of D1 and D2 receptor blockade in the PFC on foraging by rats on a radial arm maze under two task conditions: (1) a delayed task in which spatial information acquired during a training phase was used 30 min later to guide prospective responses, and (2) a nondelayed task that was identical to the test phase of the delayed task but lacked a training phase, thereby depriving rats of previous information about the location of food on the maze. In experiment 1, microinjections of the D1 antagonist SCH-23390 (0.05, 0.5, or 5 microg/&microl), but not the D2 antagonist sulpiride (0.05, 0.5, or 5 microg/microl), into the prelimbic region of the PFC before the test phase disrupted performance of the delayed task without affecting response latencies. In contrast, neither drug affected performance of the nondelayed task. In the present study, we also investigated the role of D1 receptors in modulating activity in hippocampal-PFC circuits during delayed responding. Unilateral injections of SCH-23390 into the PFC in the hemisphere contralateral to a microinjection of lidocaine into the hippocampus severely disrupted performance of the delayed task. Thus, the ability to use previously acquired spatial information to guide responding 30 min later on a radial arm maze requires D1 receptor activation in the PFC and D1 receptor modulation of hippocampal inputs to the PFC. These data suggest that D1 receptors in the PFC are involved in working memory processes other than just the short-term active retention of information and also provide direct evidence for DA modulation of limbic-PFC circuits during behavior.

Fig. 1.

Schematic representation of the SCH-23390 injection sites for rats in experiment 1. Black dotsrepresent the location of cannula tips. Illustrated brain sections are computer-generated adaptations from Paxinos and Watson (1997).

Fig. 2.

The effects of bilateral injections of D₁ or D₂ antagonists into the PL on performance of the delayed SWSh task. A, Number of errors (mean ± SEM) made during the test phase by rats receiving saline (hatched bar): 0.05, 0.5, and 5 μg of SCH-23390 (black bars) into the PL. B, Number of errors (mean ± SEM) made during the test phase by rats receiving PBS (hatched bar): 0.05, 0.5, and 5 μg of sulpiride (black bars) into the PL. *p < 0.05 compared with saline injections.

Fig. 3.

The effects of bilateral injections of D₁ or D₂ antagonists into the PL on performance of the nondelayed RF task. A, Number of errors (mean ± SEM) made during the nondelayed RF task by rats receiving saline (hatched bar): 0.05, 0.5, and 5 μg of SCH-23390 (black bars) into the PL. B, Number of errors (mean ± SEM) made during the nondelayed RF task by rats receiving PBS (hatched bar): 0.05, 0.5, and 5 μg of sulpiride (black bars) into the PL.

Fig. 4.

The effects of unilateral inactivation of the vSub in combination with unilateral injections of SCH-23390 into the PL of the contralateral hemisphere. A, Number of errors (mean ± SEM) made during the delayed SWSh task by rats on the day before the first injection (open bar), after unilateral infusions of saline into both the PL and vSub (hatched bar), unilateral infusions of SCH-23390 (SCH, 0.5 μg) into the PL and contralateral infusions of saline into the vSub (gray bar), unilateral infusions of saline into the PL and contralateral infusions of lidocaine into the vSub (vertical stripe bar), and unilateral injections of SCH-23390 (SCH, 0.5 μg) into the PL and contralateral injections of lidocaine into the vSub (black bar). **p < 0.01 versus all other treatment conditions.Inset shows the number of across-phase (cross-hatched bar) and within-phase (horizontal-striped bar) errors made by rats after the SCH/lidocaine injection condition. B, Schematic representation of the SCH-23390 injection sites into the PL and lidocaine injection sites into the vSub for rats in the SCH/lidocaine condition. Black dots represent the location of cannula tips. Illustrated brain sections are computer-generated adaptations from Paxinos and Watson (1997).