Prefrontal cortex and hippocampus subserve different components of working memory in rats

Abstract

Both the medial prefrontal cortex (mPFC) and hippocampus are implicated in working memory tasks in rodents. Specifically, it has been hypothesized that the mPFC is primarily engaged in the temporary storage and processing of information lasting from a subsecond to several seconds, while the hippocampal function becomes more critical as the working memory demand extends into longer temporal scales. Although these structures may be engaged in a temporally separable manner, the extent of their contributions in the "informational content" of working memory remains unclear. To investigate this issue, the mPFC and dorsal hippocampus (dHPC) were temporarily inactivated via targeted infusions of the GABA A receptor agonist muscimol in rats prior to their performance on a delayed alternation task (DAT), employing an automated figure-eight maze that required the animals to make alternating arm choice responses after 3-, 30-, and 60-sec delays for water reward. We report that inactivation of either the mPFC or dHPC significantly reduced DAT at all delay intervals tested. However, there were key qualitative differences in the behavioral effects. Specifically, mPFC inactivation selectively impaired working memory (i.e., arm choice accuracy) without altering reference memory (i.e., the maze task rule) and arm choice response latencies. In contrast, dHPC inactivation increased both reference memory errors and arm choice response latencies. Moreover, dHPC, but not mPFC, inactivation increased the incidence of successive working memory errors. These results suggest that while both the mPFC and hippocampus are necessarily involved in DAT, they seem to process different informational components associated with the memory task.Working memory is generally defined as cognitive entities (or "central executive" mechanisms) relating to temporary storage and operation of information in both humans and animals (Baddeley and Hitch 1974;Goldman-Rakic 1996;Fuster 2001;Dudchenko 2004). The memory may be about simple sensory stimulus, relatively complex objects, or spatial location (Olton et al. 1979;Delatour and Gisquet-Verrier 1996;Floresco et al. 1997;Hampson et al. 1999). Evidence from primate studies originally implicated the prefrontal cortex (PFC) as being crucial for working memory (Baddeley 1986;Goldman-Rakic 1987;Miller et al. 1991). For instance, damage to the PFC produces impairments in various working memory tasks in humans and non-human primates (Kolb 1990;Fuster 1997;Stuss and Alexander 2000). Additionally, recording and brain imaging studies found neural activity correlates of working memory, i.e., increased PFC activity during the delay period (Fuster and Alexander 1971;Kubota and Niki 1971;Funahashi et al. 1989).In rodents, a delayed alternation task (DAT; employing T, radial-arm, and figure-eight mazes) has been widely used to further investigate the PFC-working memory hypothesis (Murphy et al. 1996;Zahrt et al. 1997;Baeg et al. 2003Baeg et al. , 2007Schoenbaum et al. 2003;Birnbaum et al. 2004;Clinton et al. 2006). In this t...

Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes

“…Working memory requires a reciprocal network connection between the prefrontal cortex and hippocampus (45,46). Conversely, reference memory is hippocampal-dependent and persists even in the presence of prefrontal cortical inactivation (45).…”

“…Working memory requires a reciprocal network connection between the prefrontal cortex and hippocampus (45,46). Conversely, reference memory is hippocampal-dependent and persists even in the presence of prefrontal cortical inactivation (45). Because spines contribute to synaptic connectivity in cortical networks (47), the contribution of the frontal cortex to cognition may be reduced in KALRN KO mice.…”

Dysfunctional Prefrontal Cortical Network Activity and Interactions following Cannabinoid Receptor Activation

“…In rats, both hippocampus and prefrontal cortex appear to be required for working memory tasks, albeit through processing of different informational components (Yoon et al, 2008); while dorsal hippocampus is adapted to encode and process spatial information, prelimbic cortex coordinates signaling about current spatial goals (Hok et al, 2005). In essence, the exchange of information between these two structures seems to be necessary when spatial memory guides goal-directed behavior, as suggested by the hippocampal-prefrontal cortical disconnection studies (Floresco et al, 1997;Wang and Cai, 2006).…”

Age-related cognitive impairments in mice with a conditional ablation of the neural cell adhesion molecule

“…On the third day, all animals were tested for their delayed reinforced alternation performance in the T-maze, a working memory task that critically depends on both the hippocampus and the mPFC (Lalonde 2002;Runyan et al 2005;Yoon et al 2008). In this task, the animal had to choose between entering one of two arms in which a food reinforcer was present in the end of one arm.…”

“…First, we assessed their anxiety-related behaviors and locomotor activity. Next, we tested their performance in two working/episodic-like memory tests (a delayed matching-to-place [DMP] task in the Morris water maze and a delayed reinforced alternation task in the T-maze) that critically rely on the functional integrity of the hippocampus and PFC (Steele and Morris 1999;Chen et al 2000;Runyan et al 2005;Yoon et al 2008). Finally, we measured their NCAM expression levels in the hippocampus and medial PFC.…”