Glutamatergic neurotransmission in the first retinal synapse mediated by metabotropic receptors--electroretinographic study.

AIM: The aim of this study was to better characterize glutamatergic synaptic transmission between photoreceptors and retinal ON-bipolar cells. For this purpose we investigated the effect of L-serine orthophosphate (L-SOP) (an agonist of the group III metabotropic receptors) on the mass (electroretinographic) response of the ON-bipolar cells, which was obtained by isolated stimulation of the rods or the cones. MATERIALS AND METHODS: Isolated frog eyecup preparations (Rana ridibunda) were subjected to perfusion with L-SOP solution in various concentrations--10, 30, 100, 300, 500 and 1000 micromol/l. The effects of the agonist on the electroretinographic ON-response (b-wave) at isolated stimulation of the rods (adaptation to the dark, light stimuli of low intensity) or the cones (bright background illumination, stimuli of high intensity) were followed up. RESULTS: As a result of the effect of L-SOP we observed a dose-dependent decrease in amplitude and increase in peak latency of the electroretinographic (ERG) b-wave. This effect was better expressed in the responses which were mediated by the rods and even in some of the experiments the b-wave disappeared completely. As an additional effect we observed an increase of the OFF-response (the d-wave), which did not depend on the photoreceptor input. CONCLUSIONS: The mass response of the ON-bipolar cells (the b-wave in the ERG) elicited by isolated stimulation of the two kinds of photoreceptors (rods and cones) shows different sensitivity to the group III metabotropic receptor agonist L-serine-ortho-phosphate. This is indicative of a difference in the glutamatergic transmission in the synapses between the two types of photoreceptors and the retinal ON-bipolar cells.

Chromosomal microarray analysis of Bulgarian patients with epilepsy and intellectual disability.

High resolution chromosomal microarray analysis (CMA) has facilitated the identification of small chromosomal rearrangements throughout the genome, associated with various neurodevelopmental phenotypes, including ID/DD. Recently, it became evident that intellectual disability (ID)/developmental delay (DD) can occur with associated co-morbidities like epileptic seizures, autism and additional congenital anomalies. These observations require whole genome approach in order to detect the genetic causes of these complex disorders. In this study, we examined 92 patients of Bulgarian origin at age between 1 and 22 years with ID, generalized epilepsy, autistic signs and congenital anomalies. CMA was carried out using SurePrint G3 Human CGH Microarray Kit, 4 × 180 K and SurePrint G3 Unrestricted CGH ISCA v2, 4 × 180 K oligo platforms. Referral indications for selection of the patients were the presence of generalized refractory seizures disorders and co-morbid ID. Clearly pathogenic copy number variations (CNVs) were detected in eight patients (8.7%) from our cohort. Additionally, possibly pathogenic rearrangements of unclear clinical significance were detected in six individuals (6.5%), which make for an overall diagnostic yield of 15.2% among our cohort of patients. We report here the patients with clearly pathogenic CNVs, discuss the potential causality of the possibly pathogenic CNVs and make genotype - phenotype correlations. One novel possibly pathogenic heterozygous deletion in 15q22.31 region was detected in a case with ID/DD. Additionally, whole APBA2 gene duplication in 15q13.1 was found in three generations of a family with epilepsy, ID and psychiatric abnormalities. The results from this study allow us to define the genetic diagnosis in a subset of Bulgarian patients and improve the genetic counseling of the affected families. To our knowledge, this is the first aCGH evaluation of a Bulgarian cohort of children with epilepsy and ID so far.