Encoding and storage of spatial information in the retrosplenial cortex

Abstract

The retrosplenial cortex (RSC) is part of a network of interconnected cortical, hippocampal, and thalamic structures harboring spatially modulated neurons. The RSC contains head direction cells and connects to the parahippocampal region and anterior thalamus. Manipulations of the RSC can affect spatial and contextual tasks. A considerable amount of evidence implicates the role of the RSC in spatial navigation, but it is unclear whether this structure actually encodes or stores spatial information. We used a transgenic mouse in which the expression of green fluorescent protein was under the control of the immediate early gene c-fos promoter as well as timelapse two-photon in vivo imaging to monitor neuronal activation triggered by spatial learning in the Morris water maze. We uncovered a repetitive pattern of cell activation in the RSC consistent with the hypothesis that during spatial learning an experience-dependent memory trace is formed in this structure. In support of this hypothesis, we also report three other observations. First, temporary RSC inactivation disrupts performance in a spatial learning task. Second, we show that overexpressing the transcription factor CREB in the RSC with a viral vector, a manipulation known to enhance memory consolidation in other circuits, results in spatial memory enhancements. Third, silencing the viral CREB-expressing neurons with the allatostatin system occludes the spatial memory enhancement. Taken together, these results indicate that the retrosplenial cortex engages in the formation and storage of memory traces for spatial information. S patial navigation, learning, and memory depend on several interconnected brain regions. The hippocampus is known to have a central role in spatial learning and memory. Place cells in this structure form a spatial map of an animal's environment (1). The main input to the hippocampus comes from the entorhinal cortex, an area that integrates cortical inputs before forwarding them into the hippocampal formation. The dorsal medial entorhinal cortex (MEC) contains spatially modulated cells (grid cells) that fire at the nodes of a hexagonal lattice as the animal traverses its environment (2). Beyond hippocampal place cells and MEC grid cells, there is also extensive evidence for another type of spatially modulated neurons that increase firing when the animal's head points in a specific direction [head direction (HD) cells] (3). These cells reside in several subcortical and cortical regions, including the retrosplenial cortex (RSC). The RSC is one of the most important cortical afferents to MEC (4, 5). It is the most caudal part of the cingulate cortex, positioned between anterior cingulate, parietal/visual, and parahippocampal cortices. It is further subdivided into areas A29a-c (granular cortex) and area A30 (dysgranular cortex) (6). The RSC has been implicated in a number of cognitive tasks, including navigation based on external spatial (allothetic) information (7). Human functional MRI (fMRI) studies showed that the RSC is activated duri...

The cannabinoid system in the retrosplenial cortex modulates fear memory consolidation, reconsolidation, and extinction

“…The RSC also projects to the entorhinal cortex (Wyss and Van Groen 1992), another region functionally linked to the hippocampus. Previous results have already shown its involvement in emotional (Mello e Souza et al 1999;Souza et al 2002;Corcoran et al 2011;Katche et al 2013a,b) and spatial memory modulation (Czajkowski et al 2014). This is the first study to show that cannabinoid receptors in the RSC may modulate aversive memory.…”

“…The rat RSC is a very integrative area, since (a) it intermediates many signals between the hippocampal formation, thalamic regions, and the prefrontal cortex, (b) receiving information from neocortical visual, auditory, and motor areas (Hedberg and Stanton 1995;Maddock 1999;Vann et al 2009). For these reasons, it is not surprising that it is involved in emotional and spatial memory processing in both humans and rodents (Maddock 1999;Mello e Souza et al 1999;Souza et al 2002;Vogt et al 2000;Vann et al 2009;Corcoran et al 2011;Katche et al 2013a,b;Czajkowski et al 2014).…”

“…RSC activity is strongly related to the consolidation and maintenance of spatial (Czajkowski et al 2014) and aversive memories (Mello e Souza et al 1999;Souza et al 2002;Corcoran et al 2011;Katche et al 2013a,b). Our results strongly suggest that the cannabinoid receptors activation in the RSC improves contextual fear memory consolidation, since the agonist CP55940 increased freezing levels while the antagonist AM251 was amnestic.…”

Simultaneous Two-photon <em>In Vivo </em>Imaging of Synaptic Inputs and Postsynaptic Targets in the Mouse Retrosplenial Cortex

“…In this paper we propose the implantation of the cranial window above the retrosplenial cortex (RSC) as another possible region of interest for two-photon in vivo microscopy 6 . RSC is an important element of the brain circuit responsible for spatial memory formation.…”

“…Anatomically, RSC is a part of a neuronal network connecting cortical, hippocampal, and thalamic regions 7 . It is heavily involved in a range of behaviors, such as spatial learning and extinction as well as spatial navigation 6 .…”