Aberrant expression of neuropeptide Y in hippocampal mossy fibers in the absence of local cell injury following the onset of spike-wave synchronization

• Published in: Brain research. Molecular brain research. Vol. 31; no. 1; pp. 111 - 121
• Main Authors: Chafetz, Ross S., Nahm, Walter K., Noebels, Jeffrey L.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-07-1995; Elsevier
• Subjects: Action Potentials - physiology; Age of Onset; Animals; Biological and medical sciences; Cell Count; Cortical Synchronization; Dentate granule cell; Gene Expression Regulation - physiology; Glial fibrillary acidic protein; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Heat shock protein; Medical sciences; Mice; Mice, Neurologic Mutants; NADPH-diaphorase; Nerve Fibers - metabolism; Nervous system (semeiology, syndromes); Neurology; Neurons - pathology; Neuropeptide Y; Neuropeptide Y - analysis; Neuropeptide Y - genetics; Peptide trafficking; Phenotype; Point Mutation; Seizures - genetics; Seizures - pathology; Single gene mutation; Stargazer; Subcellular Fractions - chemistry; Transcriptional Activation; Neuropeptide Y; Dentate granule cell; Peptide trafficking; Single gene mutation; NADPH-diaphorase; Glial fibrillary acidic protein; Heat shock protein; Stargazer; Mossy fiber; Nervous system diseases; Epilepsy; Rodentia; Central nervous system; Gene expression; Synchronization; Cerebral disorder; Vertebrata; Mammalia; Mouse; Animal; Central nervous system disease; Spike wave; Hippocampus; Brain (vertebrata)
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/0169-328X(95)00041-P

Stargazer mutant mice inherit a recessive neuronal excitability phenotype featuring frequent non-convulsive spike-wave seizures that arise from synchronous bursting in neocortical, thalamic and hippocampal networks. Immunocytochemistry reveals that granule cells in the mutant dentate gyrus aberrantly express neuropeptide Y (NPY) at multiple ages following the developmental onset of seizures. The ectopic NPY is selectively concentrated in the mossy fibers, co-localizing with the releasable dense core vesicle pool. The NPY content of native NPY + local circuit neurons is also elevated in the mutant CNS. There is no concurrent elevation of hippocampal 72 kDa heat shock protein (HSP72), glial fibrillary acidic protein (GFAP) or NADPH-diaphorase, three markers that are induced during cellular injury, and no evidence of granule cell loss. Since mossy fiber NPY expression appears after the developmental onset of spike-wave discharges and can be induced in wild type granule cells by electrical stimulation, the altered peptide phenotype is likely to reflect transynaptic gene induction triggered by synchronous bursting. These results link a specific pattern of repetitive synaptic input with selective molecular plasticity in dentate granule cells that may contribute to dynamic modifications in hippocampal network excitability.