Hippocampus (Brain)

Experimentally naive rats show variance in their locomotor reactivity to novelty, some displaying higher (HR) while others displaying lower (LR) reactivity, associated with vulnerability to stress. LRHR phenotype is proposed as an antecedent to the development of stress hyper responsiveness. Results presented here show emergence of antidepressive-like behavior following peripubertal-juvenile exposure to chronic variable physical (CVP) and chronic variable social stress (CVS) in HR rats, and depressive-like behavior following CVP in the LRs. The antidepressive-like behavior in HR rats was accompanied by increased levels of acetylated Histone3 (acH3) and acetylated Histone4 (acH4) at the hippocampal brain-derived neurotrophic factor (BDNF) P2 and P4 promoters respectively. This effect may mediate increased mossy fibre (MF) terminal field size, particularly the suprapyramidal mossy fibre projection volume (SP-MF), in the HR animals following both stress regimens. These findings show that chronic variable stress during adolescence induces individual differences in molecular, neuromorphological and behavioral parameters between LRs and HRs, which provides further evidence that individual differences in stress responsiveness is an important factor in resistance or vulnerability to stress-induced depression and/or anxiety.

Male C7BL/6J mice were implanted with bilateral dorsal CA1 guide cannulae. After confirming that intrahippocampal microinfusion of muscimol impaired hippocampal function, demonstrated by impaired performance in the Morris water maze, the influence of intrahippocampal muscimol was tested in the Novel Object Recognition paradigm. During a test session 24 h after the last habituation/sample session, mice were presented with one familiar object and one novel object. Successful retention of object memory was inferred if mice spent more time exploring the novel object than the familiar object. Results demonstrate that muscimol infused into dorsal CA1 region prior to the test session eliminates novel object preference, indicating that the hippocampus is necessary for the retrieval of this non-spatial memory - a topic that has garnered much debate. Understanding the similarities between rodent and human hippocampal function could enable future animal studies to effectively answer questions about diseases and disorders affecting human learning and memory.

Experimentally naive rats exhibit varying degrees of novelty exploration. Some rats display high rates of locomotor reactivity to novelty (high responders; HR), and others display low rates (low responders; LR). The novelty-seeking phenotype (LRHR) is introduced as a model of stress responsiveness. In this thesis I examined effects of chronic variable physical and social stress or control handling on the levels of various neurotrophins in the hippocampus, and changes in mossy fibre terminal fields in LRHR rats. A positive correlation is seen between histone deacetylase 2 and brain-derived neurotrophic factor (BDNF) levels both of which are oppositely regulated in LRHR CA3 fields in response to chronic social stress. Increase in BDNF levels in CA3 field accompanied increase in supra-pyramidal mossy fibre terminal field size (SP-MF) in HRs, and decrease in BDNF levels accompanied decrease in SP-MF volume in LRs. Epigenetic regulation of neurotrophic support underlying these structural changes is discussed.