Synaptic mechanisms of the action of subcortical formations on motoneurons in cat facial nerve

Characteristics of the synaptic processes produced by stimulating the head of the caudate nucleus, theglocus pallidus, and the central amygaloid nucleus were investigated in motoneurons of the facial nerve during acute experiments on cats using intracellular recording techniques. It was found that stimulating the first two of these structures causes polysynaptic activation, while both mono- and polysynaptic excitation of facial nerve motoneurons are produced by stimulation of the central amygdaloid nucleus.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 17, No. 6, pp. 800–809, November–December, 1985.     

Electrophysiological features of facial motoneurons in cats

Antidromic activation of facial motoneurons in cats during stimulation of different branches of the facial nerve was studied by intracellular recording. Time and amplitude characteristics of individual components of the antidromic action potentials were analyzed and fast and slow after-potentials distinguished. Correlation was found between the duration of the descending phase of the SD spike, duration of its after-hyperpolarization, and the spike conduction time along the axon. Data were obtained to show absence of a recurrent collateral pathway in motoneurons of the facial nucleus. The functional significance of the after-potentials is discussed.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 10, No. 3, pp. 261–270, May–June, 1978.     

Synaptic mechanisms of central control of motoneuronal activity in the facial nerve nucleus

The responses of motoneurons of the facial nerve nucleus (FNN), evoked by stimulations of the oculomotor nerve nucleus, Edinger-Westphal's nucleus,substantia nigra, and entopeduncular nucleus, were studied in acute experiments on anesthetized and immobilized cats. The FNN motoneurons were identified by their antidromic activation after stimulation of various branches of the facial nerve. Stimulation of the oculomotor nerve nucleus, Edinger-Westphal's nucleus, and ipsi- or contralateral parts of thesubstantia nigra evoked mono- and polysynaptic EPSP in the FNN motoneurons, while stimulation of the entopeduncular nucleus elicited only polysynaptic EPSP. The influences from the above structures were shown to converge on the same FNN motoneurons. The findings are discussed considering morphological peculiarities of the afferent inputs to the FNN.Neirofiziologiya/Neurophysiology, Vol. 27, No. 2, pp. 116–125, March–April, 1995.     

Synaptic processes in facial motoneurons evoked by stimulation of the caudal trigeminal nucleus

Field potentials and postsynaptic potentials of facial motoneurons evoked by stimulation of the caudal trigeminal nucleus were investigated in acute experiments on cats by extra- and intra-cellular recording. Pre- and postsynaptic components of field potentials were found. Four types of motoneuron response were distinguished: EPSP with generation of single action potentials; a gradual shift of depolarization inducing grouped action potentials; a rhythmic discharge of action potentials arising at a low level of depolarization; and EPSPs or EPSP-IPSP sequences. The monosynaptic and (chiefly) polysynaptic nature of these responses was demonstrated. The possible mechanism of afferent control over facial motoneurons are discussed.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 12, No. 3, pp. 272–282, May–June, 1980.     

Involvement of the chemokine-like receptor GPR33 in innate immunity

Chemokine receptors control leukocyte chemotaxis and cell-cell communication but have also been associated with pathogen entry. GPR33, an orphan member of the chemokine-like receptor family, is a pseudogene in most humans. After the appearance of GPR33 in first mammalian genomes, this receptor underwent independent pseudogenization in humans, other hominoids and some rodent species. It was speculated that a likely cause of GPR33 inactivation was its interplay with a rodent-hominoid-specific pathogen. Simultaneous pseudogenization in several unrelated species within the last 1 million years (myr) caused by neutral drift appears to be very unlikely suggesting selection on the GPR33 null-allele. Although there are no signatures of recent selection on human GPR33 we found a significant increase in the pseudogene allele frequency in European populations when compared with African and Asian populations. Because its role in the immune system was still hypothetical expression analysis revealed that GPR33 is highly expressed in dendritic cells (DC). Murine GPR33 expression is regulated by the activity of toll-like receptors (TLR) and AP-1/NF-κB signaling pathways in cell culture and in vivo. Our data indicate an important role of GPR33 function in innate immunity which became dispensable during human evolution most likely due to past or balancing selection.     

The human genome puzzle - the role of copy number variation in somatic mosaicism

The discovery of copy number variations (CNV) in the human genome opened new perspectives in the study of the genetic causes of inherited disorders and the etiology of common diseases. Differently patterned instances of somatic mosaicism in CNV regions have been shown to be present in monozygotic twins and throughout different tissues within an individual. A single-cell-level investigation of CNV in different human cell types led us to uncover mitotically derived genomic mosaicism, which is stable in different cell types of one individual. A unique study of immortalized B-lymphoblastoid cell lines obtained with 20 year interval from the same two subjects shows that mitotic changes in CNV regions may happen early during embryonic development and seem to occur only once, as levels of mosaicism remained stable. This finding has the potential to change our concept of dynamic human genome variation. We propose that further genomic studies should focus on the single-cell level, to understand better the etiology and physiology of aging and diseases mediated by somatic variations.     

Small Supernumerary Marker Chromosomes and Uniparental Disomy Have a Story to Tell

Small supernumerary maker chromosomes (sSMC) and uniparental disomy (UPD) are rare, and a combination of both is rarely encountered. Accordingly, only 46 sSMC cases UPD have been reported. Despite of its rareness, UPD has to be considered, especially in prenatal cases with sSMC. Here, the authors reviewed all sSMC cases with UPD (sSMC^U+) and compared them to sSMC without UPD (sSMC^U−), which resulted in the following correlations: 1) every sSMC, irrespective of its chromosomal origin, may be principally connected with UPD; 2) mixed hetero- and iso-UPD (hUPD/iUPD) can be observed most often in sSMC^U+ cases followed by complete iUPD, complete hUPD, and segmental iUPD; 3) UPD of chromosomes 6, 7, 14, 15, 16, and 20 is most often reported in sSMC^U+; 4) maternal UPD was approximately nine times more frequent than paternal UPD; 5) if mosaic with a normal cell line, acrocentric-derived sSMC had a three times higher chance of occurrence than the corresponding nonmosaic sSMC cases; 6) UPD in connection with a parentally inherited sSMC is, if existent at all, a rare event; and 7) the gender type and shape of sSMC had no effect on UPD formation. Overall, sSMC^U+ cases may have a story to tell about chromosome number control mechanisms in early embryogenesis.     

Early Embryonic Chromosome Instability Results in Stable Mosaic Pattern in Human Tissues

The discovery of copy number variations (CNV) in the human genome opened new perspectives on the study of the genetic causes of inherited disorders and the aetiology of common diseases. Here, a single-cell-level investigation of CNV in different human tissues led us to uncover the phenomenon of mitotically derived genomic mosaicism, which is stable in different cell types of one individual. The CNV mosaic ratios were different between the 10 individuals studied. However, they were stable in the T lymphocytes, immortalized B lymphoblastoid cells, and skin fibroblasts analyzed in each individual. Because these cell types have a common origin in the connective tissues, we suggest that mitotic changes in CNV regions may happen early during embryonic development and occur only once, after which the stable mosaic ratio is maintained throughout the differentiated tissues. This concept is further supported by a unique study of immortalized B lymphoblastoid cell lines obtained with 20 year difference from two subjects. We provide the first evidence of somatic mosaicism for CNV, with stable variation ratios in different cell types of one individual leading to the hypothesis of early embryonic chromosome instability resulting in stable mosaic pattern in human tissues. This concept has the potential to open new perspectives in personalized genetic diagnostics and can explain genetic phenomena like diminished penetrance in autosomal dominant diseases. We propose that further genomic studies should focus on the single-cell level, to better understand the aetiology of aging and diseases mediated by somatic mutations.