Abstracts

RATIONALE: Galanin is a widely distributed neuroendocrine peptide with a variety of physiological functions, including the modulation of excitability in hippocampal circuits. Recently, three galanin receptor subtypes were cloned, and related mRNA expression for GALR1 and GALR2 localized to distinct brain areas. In the hippocampal formation, GALR2 mRNA has been found predominantly in the dentate gyrus, and GALR1 particularly in the CA1 subfield and subiculum. However, no detailed cellular-level description of galanin receptor protein distribution has yet been provided. METHODS: In the present study, we used pre- and post-embedding immunocytochemistry (GALR2 antibody from Alpha Diagnostic Intl., Inc., San Antonio, Texas) to examine the electron microscopic localization of GALR2 protein in the hippocampal formation of adult mice. RESULTS: Electron microscopic examination of brain tissue immunoreacted against GALR2 antibody revealed the following: (1) GALR2 protein is found in various brain areas, particularly hippocampal formation, entorhinal and piriform cortex, amygdala, hypothalamus and cerebellum. (2) In all regions, GALR2 immunoreactivity (IR) at the cellular level is localized within dendritic spines and dendrites-- often near the postsynaptic density, and occasionally in the cytoplasm of neuronal cell bodies associated with the endoplasmic reticulum membrane. (3) In the hippocampal formation, GALR2 IR is observed particularly in granule cell dendritic spines and dendrites, and also in hilar interneurons. Dendritic spines of hippocampal CA1 and CA3 neurons stain also for GALR2, but more sparsely. Changes in GALR2 numbers and localization, in galanin knockout and over-expressing mice, are currently under investigation. CONCLUSIONS: These observations demonstrate that GALR2 is postsynaptically localized on principal neurons of hippocampus and dentate gyrus. This pattern of GALR2 distribution and cellular localization is consistent with a role for GALR2 in modulating neuronal activity. Supported by NIH grant NS18895 and a grant from the UW Pediatric Epilepsy Research Center.