Opposing and Complementary Topographic Connectivity Gradients Revealed by Quantitative Analysis of Canonical and Noncanonical Hippocampal CA1 Inputs

Abstract

Physiological studies suggest spatial representation gradients along the CA1 proximodistal axis. To determine the underlying anatomical basis, we quantitatively mapped canonical and noncanonical inputs to excitatory neurons in dorsal hippocampal CA1 along the proximal-distal axis in mice of both sexes using monosynaptic rabies tracing. Our quantitative analyses show comparable strength of subiculum complex and entorhinal cortex (EC) inputs to CA1, significant inputs from presubiculum and parasubiculum to CA1, and a threefold stronger input to proximal versus distal CA1 from CA3. Noncanonical subicular complex inputs exhibit opposing topographic connectivity gradients whereby the subiculum-CA1 input strength systematically increases but the presubiculum-CA1 input strength decreases along the proximal-distal axis. The subiculum input strength cotracks that of the lateral EC, known to be less spatially selective than the medial EC. The functional significance of this organization is verified physiologically for subiculum-to-CA1 inputs. These results reveal a novel anatomical framework by which to determine the circuit bases for CA1 representations.

The fasciola cinereum subregion of the hippocampus is important for the acquisition of visual contextual memory

“…The more laterally extended boundaries of the FC toward the CA1 would inevitably shift the boundaries of the distal CA1 more toward the proximal CA1, possibly causing an erroneous characterization of the functions of the distal CA1. This is because it has been demonstrated that proximal and distal divisions of the CA1 receive differential inputs from the MEC and LEC, respectively; moreover, several prior studies characterized differences in the firing properties of cells along the proximodistal axis in the CA1 13,25,26 . Therefore, it is very important to clearly define the boundaries between the FC and CA1 so as to avoid mischaracterization of the physiological and functional properties of the most distal CA1 region of the hippocampus.…”

New viral‐genetic mapping uncovers an enrichment of corticotropin‐releasing hormone‐expressing neuronal inputs to the nucleus accumbens from stress‐related brain regions

“…Whereas rAAV2‐retro approach does not indicate the presence of synapses onto neurons in the NAc, it reflects the presence of axons from projecting neurons. Monosynaptic rabies tracing approaches (Sun et al, ; Sun, Nitz, Holmes, & Xu, ) can be used to label global direct synaptic inputs to NAc; immunocytochemistry could then be employed to identify the subset of those inputs that are CRH + , to determine whether NAc neurons receive direct synaptic inputs from CRH + neurons.…”

“…Monosynaptic rabies tracing approaches (Sun et al, 2014;Sun, Nitz, Holmes, & Xu, 2018) can be used to label global direct synaptic inputs to NAc; immunocytochemistry could then be employed to identify the subset of those inputs that are CRH + , to determine whether NAc neurons receive direct synaptic inputs from CRH + neurons.…”

The Neurobiology of Mammalian Navigation

“…Importantly, recent evidence shows very substantial direct projections from subiculum to CA1: in fact, the largest cortical input to distal CA1 is from the subiculum (denoted by thickest black line, Figure 4Cix) [110,111]. Moreover, while traditional lamellar slice preparations indicate information flow from CA3 towards CA1 and subiculum, more realistic (larger, longitudinal) slice preparations show theta-related information flow from subiculum towards CA3 and CA1 [112], consistent with subiculum acting as input to hippocampus.…”

“…In one speculative model, grid cells are formed from inputs involving interactions between place cells and boundary cells involving a [98], all found in medial entorhinal cortex. The strongest hippocampal formation inputs to distal CA1 come from subiculum and lateral entorhinal cortex (Cix); in turn, these regions provide the weakest inputs to proximal CA1, where instead CA3 and medial entorhinal cortex input dominate (Cx) [111]. Thickness of arrows denotes strength of projection, normalised to strongest input (subiculum strongest for distal CA1, CA3 strongest for proximal CA1), based on [111].…”