Transient inactivation of the medial prefrontal cortex impairs performance on a working memory-dependent conditional discrimination task.

Abstract

The rodent medial prefrontal cortex (mPFC) has been implicated in working memory function; lesions and inactivation of this region have been shown to result in impairments in spatial working memory tasks. Our laboratory has developed a tactile-visual conditional discrimination task, which uses floor insert cues to signal the correct goal-arm choice in a T-maze. This task can be manipulated by altering the floor insert cues to be present throughout the trial (CDSTANDARD) or present only at the beginning of the trial (CDWM), thus making the task either working-memory independent or working-memory dependent, respectively. This ability to manipulate the working memory demand of the task while holding all other task features constant allows us to rule out the possibility that confounding performance variables contributed to the observed impairment. A previous study from our lab showed that mPFC inactivation did not impair performance on CDSTANDARD, confirming that mPFC inactivation does not induce sensori-motor or motivational deficits which could impact task performance. In order to examine whether mPFC inactivation impairs CDWM, the current study transiently inactivated the mPFC with bilateral microinfusions of muscimol immediately prior to testing on the CDWM task. As predicted, CDWM task performance was significantly impaired during the muscimol-infusion session compared to the control saline-infusion sessions. Together with our previous demonstration that the mPFC in not required for CDSTANDARD, these results not only confirm that the mPFC is crucial for working memory, but also set the stage for using the task-comparison approach to investigate cortico-limbic interactions during working memory.

Inactivation of nucleus reuniens impairs spatial working memory and behavioral flexibility in the rat

“…In alternation paradigms, hippocampal lesions do not affect the ability of rats to alternate continuously in T or Y mazes, but produce delay dependent deficits—with delays ranging from seconds to several minutes (Ainge et al, ; Czerniawski et al, ; Hock and Bunsey, ; Rawlins and Olton, ; Sapiurka et al, ; Yoon et al, ). By contrast, lesions or inactivation of the medial prefrontal cortex produce delay independent effects on SWM tasks, altering performance on both continuous and delayed versions of spatial and nonspatial working memory tasks (Delatour and Gisquet‐Verrier, ; Floresco et al, ; Granon et al, ; Horst and Laubach, ; Kinoshita et al, ; Rossi et al, ; Sanchez‐Santed et al, ; Sapiurka et al, ; Shaw et al, ; Urban et al, ). The comparable effects of disruption of the HF or the mPFC on SWM are consistent with findings showing that SWM involves the interaction/cooperation of these two structures (Churchwell and Kesner, ; Spellman et al, ; Wang and Cai, ).…”

Spatial encoding in dorsomedial prefrontal cortex and hippocampus is related during deliberation

“…Also, dmPFC has been found to play an active role in the storage and recall of working memories (Cowen & McNaughton, 2007;Delatour & Gisquest-Verrier, 1999;Euston, Gruber, & McNaughton, 2012;Fuster & Alexander, 1971;Horst & Laubach, 2009;Preston & Eichenbaum, 2013;Ragozzino & Kesner, 1998;Tronel & Sara, 2003;Urban, Layfield, & Griffin, 2014;Yoon, Okada, Jung, & Kim, 2008), which may also translate to the storage of internally simulated outcome valuations. Some have theorized that dmPFC may initiate the internal construction of hypothetical situations, and use valuations of hypothetical outcomes to perform action selection (Hassabis & Maguire, 2009;van der Meer et al, 2012;Wang, Cohen, & Voss, 2015).…”

Inactivation of the nucleus reuniens/rhomboid causes a delay-dependent impairment of spatial working memory

“…One brain region involved in working memory is the medial prefrontal cortex (mPFC) (Euston et al, 2012). Lesions of the mPFC produce deficits in tasks that are thought to require the maintenance of relevant action-guiding information (Eichenbaum et al 1983; Kolb et al1994; Floresco et al 1997; Urban et al 2014). The hippocampus is another important structure for working memory in addition to its role in declarative memory (Squire, 1992; Squire, 2004) and spatial cognition (O'Keefe and Nadel, 1978; Morris et al, 1982; for review see Hartley et al, 2014).…”