Hippocampal Growth Hormone Modulates Relational Memory and the Dendritic Spine Density in CA1

Growth hormone (GH) deficiency is associated with cognitive decline which occur both in normal aging and in endocrine disorders. Several brain areas express receptors for GH although their functional role is unclear. To determine how GH affects the capacity for learning and memory by specific actions in one of the key areas, the hippocampus, we injected recombinant adeno-associated viruses (rAAVs) in male rats to express green fluorescent protein (GFP) combined with either GH, antagonizing GH (aGH), or no hormone, in the dorsal CA1. We found that aGH disrupted memory in the Morris water maze task, and that aGH treated animals needed more training to relearn a novel goal location. In a one-trial spontaneous location recognition test, the GH treated rats had better memory performance for object locations than the two other groups. Histological examinations revealed that GH increased the dendritic spine density on apical dendrites of CA1, while aGH reduced the spine density. GH increased the relative amount of immature spines, while aGH decreased the same amount. Our results imply that GH is a neuromodulator with strong influence over hippocampal plasticity and relational memory by mechanisms involving modulation of dendritic spines. The findings are significant to the increasing aging population and GH deficiency patients.