RGD Reference Report - Environmental manipulations early in development alter seizure activity, Ih and HCN1 protein expression later in life. - Rat Genome Database

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Environmental manipulations early in development alter seizure activity, Ih and HCN1 protein expression later in life.

Authors: Schridde, U  Strauss, U  Brauer, AU  Van Luijtelaar, G 
Citation: Schridde U, etal., Eur J Neurosci. 2006 Jun;23(12):3346-58.
RGD ID: 9686416
Pubmed: PMID:16820024   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1460-9568.2006.04865.x   (Journal Full-text)

Although absence epilepsy has a genetic origin, evidence from an animal model (Wistar Albino Glaxo/Rijswijk; WAG/Rij) suggests that seizures are sensitive to environmental manipulations. Here, we show that manipulations of the early rearing environment (neonatal handling, maternal deprivation) of WAG/Rij rats leads to a pronounced decrease in seizure activity later in life. Recent observations link seizure activity in WAG/Rij rats to the hyperpolarization-activated cation current (Ih) in the somatosensory cortex, the site of seizure generation. Therefore, we investigated whether the alterations in seizure activity between rats reared differently might be correlated with changes in Ih and its channel subunits hyperpolarization-activated cation channel HCN1, 2 and 4. Whole-cell recordings from layer 5 pyramidal neurons, in situ hybridization and Western blot of the somatosensory cortex revealed an increase in Ih and HCN1 in neonatal handled and maternal deprived, compared to control rats. The increase was specific to HCN1 protein expression and did not involve HCN2/4 protein expression, or mRNA expression of any of the subunits (HCN1, 2, 4). Our findings provide the first evidence that relatively mild changes in the neonatal environment have a long-term impact of absence seizures, Ih and HCN1, and suggest that an increase of Ih and HCN1 is associated with absence seizure reduction. Our findings shed new light on the role of Ih and HCN in brain functioning and development and demonstrate that genetically determined absence seizures are quite sensitive for early interventions.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
maternal behavior  IEP 9686416 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hcn1  (hyperpolarization-activated cyclic nucleotide-gated potassium channel 1)


Additional Information