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.