Figure 8.

DREADD-mediated inhibition of dorsal subiculum efferents to the ATN impairs spatial working memory. A, Sagittal schematic of rat forebrain. B, AAV5-hM4D(Gi)-mCherry expression in dorsal subiculum (coronal section, left hemisphere). All animals displayed robust expression within the dorsal subiculum as well as (C) anterograde label in the ATN (see also Fig. 6). D, Diagrammatic coronal reconstructions showing the locations of cannulae aimed at the ATN from the experimental group (ATN→SUB_iDRD) and the control group (ATN→SUB_Ctl). Numbers indicate the distance (mm) from bregma (adapted from Paxinos and Watson, 2005). The tips of the injector cannulae extend 0.5 mm beyond the end of the guide cannulae. E, DREADD activation did not reliably disrupt spatial working memory on the standard version of the alternation task, but performance was impaired on the modified version (maze rotation; Fig. 2). The DREADD group was selectively impaired relative to their performance under saline (p < 0.01) as well as to the performance of controls under clozapine (p < 0.05). Plots represent mean percentage correct. Error bars indicate SEM. AD, anterodorsal; AM, anteromedial nucleus; AV, anteroventral nucleus. *denotes statistically significant differences.