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

Supporting online material is available on Science Online

To determine how spatial scale is represented in the pyramidal cell population of the hippocampus, we recorded neural activity at multiple longitudinal levels of this brain area while rats ran back and forth on an 18-meter-long linear track. CA3 cells had well-defined place fields at all levels. The scale of representation increased almost linearly from <1 meter at the dorsal pole to~10 meters at the ventral pole. The results suggest that the place-cell map includes the entire hippocampus and that environments are represented in the hippocampus at a topographically graded but finite continuum of scales. A lthough the basic intrinsic circuitry of the hippocampus is similar along the entire dorsoventral axis of the structure (1), dorsal and ventral regions may not have similar functions. Dorsal and intermediate regions are preferentially connected, via the dorsolateral and intermediate bands of the entorhinal cortex, to visual and somatosensory cortices important for accurate spatial navigation (2-5), and selective lesions in these hippocampal regions can lead to impairments in spatial learning Conventional recording environments may be too small to visualize the most extended hippocampal representations (figs. S2 to S4 and supporting online text). Thus, we tested the animals on an 18-m-long linear track. Well-delineated place fields, defined as spatially stable contiguous regions with firing above 20% of the peak rate, could be found at all longitudinal levels of the hippocampu