INTRODUCTION
The retrosplenial cortex (RSC) plays a critical role in learning, memory, and spatial navigation. In humans, damage to the RSC via hemorrhage or tumor resulted in both anterograde and retrograde amnesia spanning up to multiple years (Chrastil, 2018; Heilman and Sypert, 1977; Ironside and Guttmacher, 1929; Todd and Bucci, 2015; Valenstein et al., 1987). Similar impacts on memory are also seen in animal studies in which the RSC is lesioned or silenced. In macaque monkeys, recall of learned images as well as the ability to learn new images was impaired when the RSC was lesioned, suggesting both retrograde and anterograde amnesic effects (Buckley and Mitchell, 2016). In rodents, lesioning the RSC worsens performance on spatial learning tasks such as the Morris Water Maze and radial arm maze, and impairs conditional learning such as tone discrimination of fear conditioned responses, suggesting the RSC is necessary for normal learning (Keene and Bucci, 2008; Sigwald et al., 2016; Todd et al., 2017, 2015; van Groen et al., 2004; Vann et al., 2003; Yamawaki et al., 2019).
Apart from its well-established contributions to memory functions, the RSC is also critical for spatial navigation (Epstein, 2008; Maguire, 2001). Human case studies show that damage to the RSC leads to disorientation in space in addition to memory impairments (Bottini et al., 1990; Ino et al., 2007; Osawa et al., 2007; Takahashi et al., 1997). Such patients can identify known scenes or locations but are unable to extract any orientation or location information from them and thus experience difficulties navigating even familiar environments (Bottini et al., 1990; Ino et al., 2007; Takahashi et al., 1997). A neuroimaging study identified the coding of head direction information in the RSC while participants navigated a novel virtual environment, suggesting that the visual cues of orientation are processed in part by the RSC during navigation (Shine et al., 2016). Many animal studies also report encoding of spatial information within the RSC, including that of head direction, position, and turning behavior (Alexander & Nitz, 2015; Cho & Sharp, 2001; Vedder et al., 2016).
The RSC’s role in memory and spatial navigation processes is accentuated in part by its extensive connections with other brain regions critical to these functions. Specifically, the granular region of the RSC (RSG) is highly interconnected with the subicular complex, CA1 of the hippocampus, the entorhinal cortex, and the anterior thalamic nuclei (van Groen and Michael Wyss, 1990; Van Groen and Wyss, 2003; Wyass and Van Groen, 1992). Regions “a” and “b” of RSG also have extensive connections with each other across the cortical layers and hemispheres. Despite the well-established dense connectivity of the RSC with other brain regions, the precise nature and properties of the neuronal subtypes involved in these connections is largely unknown (Sugar et al., 2011).
Layers 2/3 of the RSG consist of densely packed neurons (Kurotani et al., 2013; Michael et al., 1990). Here, we perform a detailed characterization of the local cell types within the superficial layers of RSG to gain insight into the local connectivity of this region and decode its computational properties. We recorded from retrosplenial slice preparations of the mouse brain to characterize the intrinsic physiology of L2/3 neurons, their local synaptic connectivity, and the computational coding schemes they are capable of. We find that the majority of neurons within this region are a distinct subtype of small pyramidal neuron that are excitatory and highly intrinsically excitable but, surprisingly, very rarely excite their neighboring inhibitory or excitatory neurons. Instead, local inhibition from fast-spiking L2/3 neurons onto these highly excitable neurons is the dominant local connectivity. Our results highlight a unique cell type and connectivity pattern that is optimally suited to selectively respond to sustained high-activity input, and likely to support the learning and memory functions of the retrosplenial cortex.