Whole-Brain Mapping the Direct Inputs of Dorsal and Ventral CA1 Projection Neurons

Abstract

The CA1, an important subregion of the hippocampus, is anatomically and functionally heterogeneous in the dorsal and ventral hippocampus. Here, to dissect the distinctions between the dorsal (dCA1) and ventral CA1 (vCA1) in anatomical connections, we systematically analyzed the direct inputs to dCA1 and vCA1 projection neurons (PNs) with the rabies virus-mediated retrograde trans-monosynaptic tracing system in Thy1-Cre mice. Our mapping results revealed that the input proportions and distributions of dCA1 and vCA1 PNs varied significantly. Inside the hippocampal region, dCA1 and vCA1 PNs shared the same upstream brain regions, but with distinctive distribution patterns along the rostrocaudal axis. The intrahippocampal inputs to the dCA1 and vCA1 exhibited opposite trends, decreasing and increasing gradually along the dorsoventral axis, respectively. For extrahippocampal inputs, dCA1 and vCA1 shared some monosynaptic projections from certain regions such as pallidum, striatum, hypothalamus, and thalamus. However, vCA1, not dCA1, received innervations from the subregions of olfactory areas and amygdala nuclei. Characterization of the direct input networks of dCA1 and vCA1 PNs may provide a structural basis to understand the differential functions of dCA1 and vCA1.

Bifurcating Neurons In The Anterior Thalamic Nuclei

“…Neuroanatomy has been used to support this difference. The Re has dense connections with hippocampal CA1, especially ventral CA1 (Hoover and Vertes, 2012; Tao et al, 2021) whereas the ATN has dense connections with the subicular cortex (Bubb et al, 2017; Mathiasen et al, 2020; Nelson, 2021). Nonetheless, the Re sends efferents to the subiculum.…”

“…Nonetheless, the Re sends efferents to the subiculum. Also, there is growing evidence that the ATN also has some projections to CA1 (de Lima et al, 2017; Prasad and Chudasama, 2013; Tao et al, 2021). In terms of memory function, not all lesion or inactivation studies are consistent, but the Re is most often associated with long-term memory consolidation rather than retrieval for spatial memory and contextual memory (de Vasconcelos and Cassel, 2015; Ferarris et al, 2021; Quet et al, 2020).…”

Transsynaptic Long-Term Potentiation in the Hippocampus of Behaving Mice

“…As far as we know, there is no report indicating the presence in mice of any noticeable direct axonal projection from the entorhinal cortex (via the PP) to the dorsal CA1 area of the contralateral hemisphere ( van Groen et al, 2003 ; Sun et al, 2018 ; Tao et al, 2021 ). Thus, the present results strongly suggest that a significant increase in synaptic strength is transsynaptically evoked by LTP induction in the PP-cCA1 synapse.…”

“…This is known to be a long-range projection (Yang and Sun, 2018), which is consistent with the larger latency observed in this study. Apparently, there is no significant direct axonal projection from the entorhinal cortex to the dorsal cCA1 area, as suggested in recently published works (van Groen et al, 2003;Sun et al, 2018;Tao et al, 2021). Consequently, for this study we focused on this disynaptic pathway to explore the transsynaptic effects of LTP.…”

All-viral tracing of monosynaptic inputs to single birthdate-defined neurons in the intact brain

“…As a result, the different hippocampal subfields and firing properties of the principal cell types within it, as well as the gross connectivity of the circuit, are well understood. Monosynaptic rabies tracing has been used previously to identify inputs to large populations of hippocampal neurons ( Nakashiba et al., 2012 ; Deshpande et al., 2013 ; Sun et al., 2014 , 2017 ; Tao et al., 2021 ) and, very recently, also inputs to individual CA1 pyramidal cells ( Geiller et al., 2021 ). However, the constellation of inputs that single cells in deeper hippocampal subfields receive remains unknown.…”