Behavior‐driven arc expression is reduced in all ventral hippocampal subfields compared to CA1, CA3, and dentate gyrus in rat dorsal hippocampus

Abstract

Anatomical connectivity and lesion studies reveal distinct functional heterogeneity along the dorsal-ventral axis of the hippocampus. The immediate early gene Arc is known to be involved in neural plasticity and memory and can be used as a marker for cell activity that occurs, for example, when hippocampal place cells fire. We report here, that Arc is expressed in a greater proportion of cells in dorsal CA1, CA3, and dentate gyrus (DG), following spatial behavioral experiences compared to ventral hippocampal subregions (dorsal CA1 = 33%; ventral CA1 = 13%; dorsal CA3 = 23%; ventral CA3 = 8%; and dorsal DG = 2.5%; ventral DG = 1.2%). The technique used here to obtain estimates of numbers of behavior-driven cells across the dorsal-ventral axis, however, corresponds quite well with samples from available single unit recording studies. Several explanations for the two- to-threefold reduction in spatial behavior-driven cell activity in the ventral hippocampus can be offered. These include anatomical connectivity differences, differential gain of the self-motion signals that appear to alter the scale of place fields and the proportion of active cells, and possibly variations in the neuronal responses to non-spatial information within the hippocampus along its dorso-ventral axis.

Place navigation in the Morris water task results in greater nuclear Arc mRNA expression in dorsal compared to ventral CA1

“…It is possible that the differences in our results might be due to the IEG marker quantified, the subregion assessed, the task used to promote IEG expression, or how the active population was estimated using design‐based stereology, rather than using selective and exhaustive counting methods. Although, we have not found evidence in the MWT that goal location or global context affect the number of active cells in CA1, we did observe reliably greater activation in dorsal compared to ventral regions across groups—corroborating previous findings that dorsal hippocampus has a greater activation than the ventral hippocampus in dry‐land navigation tasks and random spatial sampling in rats (Chawla et al, ). While we have investigated how changes to global context affect the number of active cells across the CA1 dorsal–ventral axis, future work might investigate how changes to goal location or global context in a similar task affect rate and population coding schemes in CA1 using more fine‐grained tools for observation to characterize remapping effects in these subregions.…”

“…When the platform was moved to the opposite pool quadrant (PLACE group) animals took significantly longer to navigate to the newly correct location than if the platform remained in the same location (SAME group; p < .0001) or if the platform was relocated in a new room (ROOM group; p < .0001). The ROOM group also took significantly longer to navigate to the new goal location compared to SAME rats (p < .05; Two-way ANOVA: d) Session F(1, 21) = 39.86, p < .0001; Group F(2, 21) = 18.43, p < .0001; Interaction F(2, 21) = 30.47, p < .0001) memory representation is greater in dorsal compared to ventral CA1, which is based on observations of smaller place field size in the dorsal hippocampus, and the impaired precision in place navigation memory following dorsal hippocampal damage (Chawla et al, 2018;Jung et al, 1994;Strange et al, 2014). This view implies that more cells are active in dorsal regions due to a fine-grained representation that requires more cells, representing less information, are active when a memory is retrieved.…”

“…The MWT is the most popular behavioral assay of place navigation memory in rodents. While many dorsal–ventral functional differences in hippocampal lesion studies have been reported in the MWT (Ferbinteanu & McDonald, , ; McDonald et al, ; Moser et al, , ; Ruediger et al, ), differences in cellular activation were found during random spatial sampling and navigation in dry‐land tasks (Chawla et al, ). Here, we sought to determine if dorsal–ventral activation differs in CA1 during place navigation in the MWT by measuring nuclear Arc mRNA expression, which has previously been found to increase following spatial navigation (Guzowski, Setlow, Wagner, & McGaugh, ), and whether changes to goal location or spatial context affect cellular activation probability as previously suggested (Bye & McDonald, ; Vann et al, ).…”

“…Two accounts of dorsal–ventral hippocampal functional differences might explain our observations of activation patterns in dorsal and ventral CA1 in the MWT. One account is that the granularity of memory representation is greater in dorsal compared to ventral CA1, which is based on observations of smaller place field size in the dorsal hippocampus, and the impaired precision in place navigation memory following dorsal hippocampal damage (Chawla et al, ; Jung et al, ; Strange et al, ). This view implies that more cells are active in dorsal regions due to a fine‐grained representation that requires more cells, representing less information, are active when a memory is retrieved.…”

Increased molecular plasticity along the septotemporal axis of the hippocampus is associated with network functioning

“…These, represent endogenous mechanistic aspects of the more general concept of functional segregation along the dorsoventral axis of hippocampus postulating that specific behavioral functions can be ascribed to distinct segments along the hippocampal formation, usually and shortly expressed by a dichotomy between cognition and emotionality related processes undertaken by the dorsal (DH) and the ventral hippocampus (VH) respectively (Bannerman et al 2014;Strange et al 2014;Gulyaeva 2018). The recently revealed striking diversification in patterns of gene expression along the hippocampus (Sotiriou et al 2005;Pandis et al 2006;Gusev et al 2005;Leonardo et al 2006; Thompson et al 2008;Dong et al 2009;Snyder et al 2011;Cembrowski et al 2016;Lee et al 2017;Chawla et al 2018;Floriou-Servou et al 2018), may have profound functional implications for the hippocampal circuitry and the higher-level functional diversification along hippocampus. However, though some dorsal-ventral differences, for instance in synaptic and cell level have been successfully linked to molecular diversity along the hippocampus (Pandis et al 2006;Dubovyk and Manahan-Vaughan 2018a;Snyder et al 2011;Zhu et al 2018;Floriou-Servou et al 2018;Dubovyk and Manahan-Vaughan 2018b), the functional implications of diversified patterns of gene expression are largely unknown (Tushev and Schuman 2016).…”