Effect of juvenile pretraining on adolescent structural hippocampal attributes as a substrate for enhanced spatial performance

Abstract

Research has demonstrated that Long -Evans rats (LER) display superior mnemonic function over Wistar rats (WR). These differences are correlated with endogenous and input-dependent properties of the hippocampus. The present work sought to determine if juvenile pretraining might enhance hippocampal structural markers and if this would be associated with spatial processing improvements. Male and female WR and LER were either handled or trained on a water maze task from postnatal day 16 (p16) to p26 (pretraining). All animals were then trained on the task from p40 to p44 followed by immunohistochemical assessment of synaptophysin (to mark presynaptic terminals), MAP-2 (to mark dendrites), and the phosphorylated (activated) form of the extracellular signal-regulated kinase-1 (pERK1) in the hippocampus. From p19 to p20, LER (both male and female) showed a dramatic improvement in locating the hidden platform compared to their WR counterparts. On the first day of training at p40, all pretrained groups showed shorter latencies to locate the platform compared to groups without pretraining. Over the next 4 d, only pretrained male LER showed enhanced memory. Immunohistochemical analysis revealed fewer pERK1-labeled neurons in the CA3 hippocampal region in all pretrained groups and fewer pERK1-labeled neurons in the CA1 region of pretrained male LER. Pretrained male LER also showed more MAP-2 staining in CA1 and dentate gyrus regions. Synaptophysin staining revealed a pattern of axonal redistribution in the CA3 region in the pretrained groups. Results suggest a pattern of structural hippocampal alterations that may help to identify network malleability following pretraining protocols.

Part II: Strain- and sex-specific effects of adolescent exposure to THC on adult brain and behaviour: Variants of learning, anxiety and volumetric estimates

“…One possible explanation may be the use of different laboratory rat strains, which can differ drastically in both behaviour and drug response. For example, the Long-Evans hooded (LER) strain outperforms the Wistar (WR) strain in the standard Morris water task (MWT) [39], displays differential cytoarchitecture in the hippocampus [39] and benefits from juvenile MWT pretraining [40]. Rat strain and sex can also interact.…”

“…Rat strain and sex can also interact. For example, only LER males, and not females, benefit from juvenile pretraining in the MWT [40]. Also, LER females reach puberty earlier than WR females, but this is not observed in males [30].…”

Structural Development of Hippocampal CA3 Pyramidal Neurons and Relation to the Development of Spatial Learning and Memory in Rats

“…Thus presynaptic component of DG-CA3 thorny excrescences may enhance spatial processing on a variety of spatial tasks such as the MWM task. In addition, it is speculated that juvenile rats at p24 would exhibit more and larger thorny excrescences than that of rats in p18, p20, and p22 as it is the time 10 that rats reach maturity in spatial learning and memory (Rudy, Stadler-Morris & Albert, 1987;Keeley, Wartman, Hausler & Holahan, 2010).…”

“…The sensitive developmental period of the dentate gyrus-CA3 (from p16 to p24) in LER has been behaviorally tested (Rudy, Stadler-Morris & Albert, 1987;Keeley, Wartman, Hausler & Holahan, 2010). The development of spatial navigation behaviors using proximal and distal cues was examined in LER rats (Rudy, Stadler-Morris & Albert, 1987).…”

The Effects of Early-Life Phthalate Exposure on Prefrontal Cortex Mediated Behaviours

“…The PFC is one of the last brain regions to mature (Teffer and Semendeferi, 2012), with ongoing dopaminergic innervation occurring throughout adolescence (Kalsbeek et al, 1988). The sensitive hippocampal period of development is marked by extensive synaptic growth and remodeling, with increases in mossy fiber projections from the dentate gyrus (DG) to the pyramidal neurons (Holahan et al, 2007;Keeley et al, 2010). As will be discussed in further detail in the following sections, exposure to environmental insults during any of these critical periods could disrupt these developmental processes, resulting in long-lasting deficits.…”