WITHDRAWN: Excitatory effects of dentate gyrus mossy cells on granule cells and area CA3: an vitro and in vivo study in adult mice

Abstract

Glutamatergic dentate gyrus (DG) mossy cells (MCs) innervate the primary cell type, granule cells (GCs), and GABAergic neurons which inhibit GCs. Prior studies suggest that the net effect of MCs is mainly to inhibit GCs, leading one to question why direct excitation of GCs is often missed. We hypothesized that MCs do have excitatory effects, but each GC is only excited weakly, at least under most experimental conditions. To address this hypothesis, MC axons were stimulated optogenetically in slices. A brief optogenetic stimulus to MC axons in the inner molecular layer (IML) led to a short-latency field EPSP (fEPSP) in the IML, suggesting there was a direct excitatory effect on GCs. Population spikes were negligible however, consistent with weak excitation. FEPSPs reflected AMPA/NMDA receptor-mediated EPSPs in GCs. EPSPs reached threshold after GC depolarization or facilitating NMDA receptors. GABAA and GABAB receptor-mediated IPSPs often followed EPSPs. At the network level, an conditions. This view is consistent with a network where there is selective activation of GCs, optimal for a function of the DG that has received much attention: pattern separation (Leutgeb et al.

Dorsal and ventral mossy cells differ in their long-range axonal projections throughout the dentate gyrus of the mouse hippocampus

“…Consistent with previous reports (Bernstein et al, 2020;Botterill et al, 2019), hilar GFP cell bodies near the injection site strongly colocalized with the glutamatergic marker GluR2/3 ( Figure S1). GFP axons in dorsal DG were primarily restricted to the IML ( Figure 1C1-C3).…”

“…In contrast, the MOPP cell and neurogliaform cells have an axon that is localized to the area around their somata and this includes both the OML and MML (Armstrong et al, 2011;Halasy and Somogyi, 1993). Notably, the Drd2-Cre mouse has been suggested to show expression of Cre not only in MCs but also some hippocampal GABAergic neurons (Puighermanal et al, 2015), but we have found this rare (Bernstein et al, 2020;Botterill et al, 2019). Nevertheless, in the present paper we used two markers of GABAergic neurons and asked if there was colocalization of viral expression of MCs with GABAergic neuron labeling.…”

“…In Crlr-Cre mice, it has been suggested that ventral CA3 pyramidal cells can be labeled by virus (Bernstein et al, 2020;Jinde et al, 2012). Therefore, the potential expression of virus in CA3 pyramidal cells was important to consider.…”

“…The robust nature of Cre-dependent viral labeling in both of these lines is well documented (Azevedo et al, 2019;Botterill et al, 2019;Jung et al, 2019;Oh et al, 2019;Puighermanal et al, 2015;Senzai and Buzsaki, 2017;Yeh et al, 2018). Several studies have now used these Cre lines to evaluate effects of MC manipulations in vivo or in vitro (Azevedo et al, 2019;Bernstein et al, 2020;Botterill et al, 2019;Jinde et al, 2012;Jung et al, 2019;Oh et al, 2019;Puighermanal et al, 2015;Senzai and Buzsaki, 2017;Yeh et al, 2018). However, these mouse lines are also useful to address the MC axon projections in the adult mouse.…”

Bidirectional regulation of cognitive and anxiety-like behaviors by dentate gyrus mossy cells in male and female mice

“…Viral expression in Drd2-Cre +/mice was characterized by large hilar mCherry + cells proximal to the injection site and a dense band of mCherry + labeling in the inner molecular layer (IML) throughout the septotemporal axis of the DG, consistent with the location of MCs and their major axon projection ( Figure 1C-D; Scharfman, 2016). The pattern of viral expression has been validated in previous work by our laboratory (Botterill et al, 2019;Bernstein et al, 2020) and confirmed by others (Danielson et al, 2017;Bui et al, 2018;Yeh et al, 2018;Azevedo et al, 2019;Oh et al, 2019).…”