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...

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Emerging evidence suggests that the hippocampus can be anatomically and functionally dissociated along its septotemporal axis into dorsal and ventral subregions. With respect to function, we have recently demonstrated that pre-training excitotoxic lesions of ventral, but not dorsal, hippocampus impair the acquisition of trace fear conditioning, whereas post-training lesions of either dorsal or ventral hippocampus impair the subsequent expression of trace fear conditioning (Yoon and Otto (2007) Neurobiol Learn Mem 87:464-475). In addition to trace fear conditioning, dorsal and ventral hippocampus appear to be differentially involved in a number of spatial memory tasks. The present study examined the effects of temporary inactivation of dorsal or ventral hippocampus on the acquisition and expression of trace fear conditioning and on performance of a spatial delayed reinforced alternation task. The findings demonstrate a double dissociation of dorsal and ventral hippocampal function: inactivation of ventral, but not dorsal, hippocampus attenuated the acquisition and expression of trace fear conditioning, whereas inactivation of dorsal, but not ventral, hippocampus dramatically impaired performance in the delayed reinforced alternation task. These data further support the notion that dorsal and ventral hippocampus contribute differentially to performance in a variety of paradigms.

The medial prefrontal cortex (mPFC) has been studied for its role in various cognitive functions, but the roles of its subregions remain unclear. We performed tetrode recordings simultaneously from prelimbic (PL) and rostral (rACC) and caudal (cACC) anterior cingulate subregions of the rabbit mPFC to understand their interactions during learning and tests of remote memory retention for whiskersignaled trace eyeblink conditioning. cACC neurons exhibited an innate response to the conditioning stimulus (CS) that rapidly decreased across sessions, suggesting an attentional role for facilitating CS-US associations. rACC neurons from conditioned rabbits exhibited robust responses to the CS that decreased within each session, possibly evaluating its emotional salience. PL neurons exhibited robust persistent activity during the trace interval during tests of remote memory retention, suggesting its involvement in retrieval and execution of a consolidated response. Mechanistically, conditioning was associated with a greater percentage of persistently responsive neurons than neurons from pseudoconditioned control rabbits, and responses differed significantly between trials with and without conditioned responses. Collectively, these responses reflect a functional reorganization of neural activity within the prefrontal network from an attentional mode to one that orchestrates the retrieval and execution of the learned response.

Strain and sex differences in fear conditioning were investigated in two commonly used laboratory rats: Sprague Dawleys and Long-Evans. Twenty-two kHz ultrasonic vocalization (USV) distress calls and freezing behavior were used to measure fear responses to contextual and auditory conditioned stimuli (CSs), which were previously paired with a footshock unconditioned stimulus (US). Both strain and sex had significant effects on USVs and freezing during training and subsequent context and tone tests. Overall, the male Sprague Dawley rats froze and emitted USVs more than the other groups. Additionally, levels of freezing and USVs were differentially influenced by the type of CS (context or tone). These results suggest that species-specific defense responses in laboratory rats are highly influenced by the strain and sex of the subject, and that these factors should be considered in future fear conditioning studies.