TY  - JOUR
AB  - Spatial representations enable navigation from early life on. However, the brain regions essential to form spatial representations, like the hippocampus, are considered functionally immature before weaning. Here, we examined the formation of representations of space in rat pups on postnatal day (PD) 16, using a simple habituation paradigm where the pups were exposed to an arena on three occasions, separated by ~140 min. Whereas on the first two occasions the arena was the same, on the third “test” occasion either proximal cues (Prox group), or distal cues (Dist group), or proximal and distal cues (Prox-Dist group), or no cues (No-change group) were rearranged. Locomotion (distance traveled) was used as behavioral measure of habituation, and c-Fos expression to measure regional brain activity at test. Locomotion generally decreased across the first two occasions. At test, it reached a minimum in the No-change group, indicating familiarity with the spatial conditions. By contrast, the Prox-Dist group displayed a significant increase in locomotion which was less robust in the Prox group and absent in the Dist group, a pattern suggesting that the pups relied more on proximal than distal cues during spatial exploration. c-Fos activity in the No-change group was significantly suppressed in the hippocampus (CA1, CA3, dentate gyrus) but simultaneously enhanced in the prelimbic area (PL) of the medial prefrontal cortex, compared with untreated Home-cage controls, pointing to a possible involvement of the PL in regulating locomotion in familiar spaces. By contrast, in both Prox-Dist and Prox groups c-Fos activity was enhanced in hippocampal CA1 and CA3 regions, suggesting these regions might be particularly involved in regulating exploration of spatial novelty. Our findings show that functional representations of space at a systems level are formed already in pre-weanling rats.
AU  - Shan, X.*
AU  - Contreras, M.P.*
AU  - Mendez, M.*
AU  - Born, J.
AU  - Inostroza, M.*
C1  - 63554
C2  - 51580
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Unfolding of spatial representation at systems level in infant rats.
JO  - Hippocampus
PB  - Wiley
PY  - 2021
SN  - 1050-9631
ER  - 

TY  - JOUR
AB  - Expression of the lacZ-sequence is a widely used reporter-tool to assess the transgenic and/or transfection efficacy of a target gene in mice. Once activated, lacZ is permanently expressed. However, protein accumulation is one of the hallmarks of neurodegenerative diseases. Furthermore, the protein product of the bacterial lacZ gene is ß-galactosidase, an analog to the mammalian senescence-associated ß-galactosidase, a molecular marker for aging. Therefore we studied the behavioral, structural and molecular consequences of lacZ expression in distinct neuronal sub-populations. lacZ expression in cortical glutamatergic neurons resulted in severe impairments in hippocampus-dependent memory accompanied by marked structural alterations throughout the CNS. In contrast, GFP expression or the expression of the ChR2/YFP fusion product in the same cell populations did not result in either cognitive or structural deficits. GABAergic lacZ expression caused significantly decreased hyper-arousal and mild cognitive deficits. Attenuated structural and behavioral consequences of lacZ expression could also be induced in adulthood, and lacZ transfection in neuronal cell cultures significantly decreased their viability. Our findings provide a strong caveat against the use of lacZ reporter mice for phenotyping studies and point to a particular sensitivity of the hippocampus formation to detrimental consequences of lacZ expression.
AU  - Reichel, J.M.*
AU  - Bedenk, B.T.*
AU  - Gassen, N.*
AU  - Hafner, K.*
AU  - Bura, S.A.*
AU  - Almeida-Correa, S.*
AU  - Genewsky, A.*
AU  - Dedic, N.*
AU  - Giesert, F.
AU  - Agarwal, A.*
AU  - Nave, K.A.*
AU  - Rein, T.*
AU  - Czisch, M.*
AU  - Deussing, J.M.*
AU  - Wotjak, C.T.*
C1  - 48463
C2  - 41161
CY  - Hoboken
SP  - 1250-1264
TI  - Beware of your Cre-Ation: lacZ expression impairs neuronal integrity and hippocampus-dependent memory.
JO  - Hippocampus
VL  - 26
IS  - 10
PB  - Wiley-blackwell
PY  - 2016
SN  - 1050-9631
ER  - 

TY  - JOUR
AB  - Radial glia-like cells (RGCs) are the hypothesized source of adult hippocampal neurogenesis. However, the current model of hippocampal neurogenesis does not fully incorporate the in vivo heterogeneity of RGCs. In order to better understand the contribution of different RGC subtypes to adult hippocampal neurogenesis, we employed widely used transgenic lines (Nestin-CreERT2 and GLAST::CreERT2 mice) to explore how RGCs contribute to neurogenesis under basal conditions and after stimulation and depletion of neural progenitor cells. We first used these inducible fate-tracking transgenic lines to define the similarities and differences in the contribution of nestin- and GLAST-lineage cells to basal long-term hippocampal neurogenesis. We then explored the ability of nestin- and GLAST-lineage RGCs to contribute to neurogenesis after experimental manipulations that either ablate neurogenesis (i.c.v. application of the anti-mitotic AraC, cytosine-β-D-arabinofuranoside) or stimulate neurogenesis (wheel running). Interestingly, in both ablation and stimulation experiments, labeled RGCs in GLAST::CreERT2 mice appear to contribute to neurogenesis, whereas RGCs in Nestin-CreERT2 mice do not. Finally, using NestinGFP reporter mice, we expanded on previous research by showing that not all RGCs in the adult dentate gyrus subgranular zone express nestin, and therefore RGCs are antigenically heterogeneous. These findings are important for the field, as they allow appropriately conservative interpretation of existing and future data that emerge from these inducible transgenic lines. These findings also raise important questions about the differences between transgenic driver lines, the heterogeneity of RGCs, and the potential differences in progenitor cell behavior between transgenic lines. As these findings highlight the possible differences in the contribution of cells to long-term neurogenesis in vivo, they indicate that the current models of hippocampal neurogenesis should be modified to include RGC lineage heterogeneity.
AU  - DeCarolis, N.A.*
AU  - Mechanic, M.*
AU  - Petrik, D.*
AU  - Carlton, A.*
AU  - Ables, J.L.*
AU  - Malhotra, S.*
AU  - Bachoo, R.*
AU  - Götz, M.
AU  - Lagacen, D.C.*
AU  - Eisch, A.J.*
C1  - 24712
C2  - 31647
SP  - 708-719
TI  - In vivo contribution of nestin- and GLAST-lineage cells to adult hippocampal neurogenesis.
JO  - Hippocampus
VL  - 23
IS  - 8
PB  - Wiley-Blackwell
PY  - 2013
SN  - 1050-9631
ER  -