Archaic Pentatonic Melodies in Pindus Mountain –Range in Northern Greece. The hemitonic and anhemitonic pentatonic tunings in Greece and their contribution to the interpretation of early Ancient Greek musical forms

The hemitonic pentatonic tuning in Western Greece attested by the author and the anhemitonic tuning previously documented in the area of Epirus but apparently present in all Western Greece, were two main reasons for the investigation and classification of the co-related micro-scales found in the wider area of Pindus. Though many scholars both Greeks and others managed to explain the peculiarities of this musical system found in Western Greece and today’s Southern Albania (Northern Epirus), they failed to do so, as they attributed specific functionalities of the system to simple imitations of instrumental practices. Nonetheless extensive field research in the area of Pindus and in Northern Epirus reveal important correspondences between the function of the melodies of this contemporary system and the “obscure” information about the evolution of the musical system in Greek (and one might generally say) in Balkan antiquity. Two dimensions of this musical system are of great importance in relation to the ancient sources. The first is that hemitonic pentatonism (a tuning responsible for the genesis of the enharmonic genus in Antiquity) is still a part of the contemporary musical system in the Greek mainland. The other is that the combination of the two pentatonic tunings reveals a process that can come to a heptachord system existing in its on right. The functionality of the micro-scales also reveal in a unique way the importance of the witness of Nichomachus regarding the evolutionary process for the genesis of the octachord out of the heptachord system and the witness of Aristotle regarding the co-existence of two heptachord systems one “diatonic” and the other anhemitonic. Apart from the above conclusions, evaluating this data makes clear that it was possible for a diatonic heptachord system to appear by a combination of the two systems: the hemitonic and anhemitonic pentatonic. This information deviates from the theory of the blown fifths as it is based on vocal music

“Shifting” Identities or “Hidden” Messages? A Musical Ethnohistory of Northwestern Greece (An Introductory Note)

This research explores the musical culture of an unknown area of Northwestern Greece (Western Macedonia and Epirus) and its neighboring areas in the State of North Macedonia and Northern Epirus in Southern Albania. It reveals that areas considered alien and linguistically distinguished from each other, belong to the same musical culture despite the difference of language. Thus the conventional division of the area of Western Macedonia in Greece into three zones, the Greek-speaking part (the largest one), the Vlach-speaking part (on the Pindus Mountains), and the Slav-speaking, on the Northern part of the area, is seriously disputed. Emic comments of the locals about their language and identity, justify these findings and are confirmed by historical research in the Byzantine past of the area

Arhaični elementi u vokalnoj muzičkoj tradiciji planinskog stanovništva severne Grčke - rezultati istraživanja sprovedenog među Vlasima i Grcima iz oblasti severnog Pinda u Grčkoj

In the region of Pindus (Epirus) we find, among others, hemitonic pentatonic scales in which the semitone is below a major third. Such melodic movements bear marked similarities with the description in the pseudo-Plutarch of the birth of the enharmonic genus. These data from history are confirmed in practical form by ethno musicological research into the vocal music of the northern Pindus, both Grecophone and Vlachophone. Comparative research into other musical idioms of the Balkans and central Europe might enlighten us as to the existence of a common, older European substratum.U oblasti Pinda i šire, Epira, zapadne Makedonije i Tesalije osim pentatonskih nepolustepenih lestvica nalazimo i polustepene pentatonske skale. U ovim poslednjim zapažamo da se polustepen nalazi ispod velike terce i to, posebno, u silaznom melodijskom pokretu - u glisandu. Polustepen ponekad ostaje nedeljen, no mnogo češće, pri silaznom kretanju zapažamo naglašeni skok glasa u predelu polustepena, koji ga u suštini deli na četvrt tona. Ovakvi melodijski pokreti ukazuju na nesumnjive analogije sa opisom Pseudoplutarha u vezi sa obrazovanjem enharmonskog lestvičnog roda koji je proizašao iz arhaičnog polustepenog pentatonskog tetrahorda ili pentahorda čiji je, pak, suštinski razvoj bio u vezi sa podelom prvobitno nedeljivog polustepena u njegovoj osnovi. Informacije Pseudoplutarha se odnose na razvoj arhaične muzike jelinskog podneblja i one svedoče o konkretnim melodijskim pokretima kojima su se odlikovale prve arhaične melodije. Ovi elementi, do kojih dolazimo na osnovu muzikološko-istorijskih istraživanja bivaju posvedočeni i razumljivi u praktičnim etnomuzikološkim proučavanjima vlaške i grčke vokalne muzike u oblasti severnog Pinda. U melodijama Epira zapadne Makedonije i Tesalije, naime, polustepen u osnovi polustepenog pentatonskog tetrahorda biva razdeljen karakterističnim glisandima. Uporedna istraživanja i drugih muzičkih idioma u planinskim oblastima Balkana i centralne Evrope mogla bi da dovedu do starijeg i ujedno zajedničkog muzičkog sloja

Cortical circuit and behavioural pathophysiology in rodent models of SYNGAP1 haploinsufficiency

SYNGAP1 haploinsufficiency is one of the most common monogenic causes of nonsyndromic moderate to severe intellectual disability (NSID) and autism (Hamdan et al., 2009; Pinto et al., 2010). De novo truncating or frameshift mutations in the SYNGAP1 gene lead to the loss of the encoded protein Synaptic GTPase activating protein (SynGAP), one of the most abundant of postsynaptic proteins (Hamdan et al., 2011). SynGAP, present at excitatory and inhibitory synapses (Kim et al., 1998), acts as a key regulator of highly conserved signaling pathways linked to AMPA- and NMDA-receptor dependent plasticity at the post synaptic density (Krapivisky et al., 2004; Vazquez et al., 2004). The Syngap mouse model has been extensively used to understand the pathophysiology underlying abnormal SynGAP-mediated signaling. Syngap heterozygous (het) mice demonstrate a range of physiological and behavioural abnormalities from development to adulthood (Komiyama et al., 2002; Muhia et al., 2010). However, recent advances in techniques for genome manipulation have allowed for the generation of rat models of neurodevelopmental disorders, including Syngap; enabling phenotypes to be validated across species and to address cognitive and social dysfunction, using paradigms that are more difficult to assess in mice. In this study, we examined the pathophysiology associated with a heterozygous deletion of the C2 and catalytic GAP domain of the protein, in Long-Evans rats (het). In contrast with het mice, het rats do not present with hyperactivity and can be habituated to an open field environment. To examine associative recognition memory, we tested the rats in five spontaneous exploration tasks for short-term and long-term memory, object-recognition (OR), object-location (OL), object-place (OP), object-context (OC) and object-place-context (OPC). Both groups were able to perform short-term memory tasks, but only wild type rats performed above chance in OL with a 24hour delay, suggesting deficits in long- term spatial memory. We also tested if partial loss of the GAP domain in SynGAP affects social behaviour in rats and we found that het rats exhibited impaired short- term social memory, with no signs of social isolation. These findings do not fully recapitulate previous abnormalities reported in the mouse model of SYNGAP1 haploinsufficiency, suggesting that some key behavioural phenotypes may be species-specific. Furthermore, based on physiological deficits that Syngap het mice exhibit, such as alterations in mEPSC/mIPSC amplitude and frequency and evoked cortical hyperexcitability in vitro (Guo et al., 2009; Ozkan et al., 2014), we also aimed to test if in vivo neuronal activity and circuit properties are altered. Using two-photon calcium imaging in awake mice, we focused on two areas of the cortex; a primary sensory area, the binocular region of the visual cortex (V1), and an association area, the medial posterior parietal cortex (PPC). Both areas have been found to maintain activity during visual discrimination tasks but to present with divergent activity trajectories (Harvey et al., 2012; Goard et al., 2016). We found preliminary evidence that neurons in layer 2-3 of the PPC of Syngap mice are hypoactive in basal conditions when animals are still in the dark, compared to wild type controls. When we assessed whether that changes when animals are running, we found that during locomotion neurons of both genotypes increase their activity, consistent with previous findings in wild type mice (McGinley et al., 2015; Pakan et al., 2016). However, this response gain is exaggerated in Syngap het neurons of the PPC. In contrast to above findings in PPC, results in V1 show that layer 2-3 neurons are hyperactive during both behavioural states, suggesting seemingly different computations of these two cortical areas. This work provides the first evidence for a dysregulated neuronal circuit in vivo in both visual and parietal cortex of Syngap mice, two areas critical for sensory processing that has been found to be affected in individuals with NSID and autism (Joosten and Bundy, 2010). We also provide first evidence of the effect of loss of SynGAP activity in behaviour of rats, complimenting existing data in the literature in a species-specific manner and providing greater insight into sensory and cognitive dysfunction associated with dysregulation in SynGAP-mediated signaling

Attentional effects on local V1 microcircuits explain selective V1-V4 communication

Selective attention implements preferential routing of attended stimuli, likely through increasing the influence of the respective synaptic inputs on higher-area neurons. As the inputs of competing stimuli converge onto postsynaptic neurons, presynaptic circuits might offer the best target for attentional top-down influences. If those influences enabled presynaptic circuits to selectively entrain postsynaptic neurons, this might explain selective routing. Indeed, when two visual stimuli induce two gamma rhythms in V1, only the gamma induced by the attended stimulus entrains gamma in V4. Here, we modeled induced responses with a Dynamic Causal Model for Cross-Spectral Densities and found that selective entrainment can be explained by attentional modulation of intrinsic V1 connections. Specifically, local inhibition was decreased in the granular input layer and increased in the supragranular output layer of the V1 circuit that processed the attended stimulus. Thus, presynaptic attentional influences and ensuing entrainment were sufficient to mediate selective routing

Conventional Epi-LASIK and Lamellar Epithelial Debridement in Myopic Patients with Dermatologic Keloids

We report the outcome of conventional epipolis laser in situ keratomileusis (Epi-LASIK, flap-on) and lamellar epithelial debridement (LED; Epi-LASIK, flap-off) in myopic patients with dermatologic keloids. Three patients, who were all noted to be susceptible to keloid scarring, received conventional Epi-LASIK in their right eyes and LED in their left eyes. The patients were followed-up for 6 to 21 months after their surgeries, and the outcomes were then evaluated. In case 1, the preoperative spherical equivalent (SE) was -6.5 diopters (D) in the right eye (OD) and -6.25 D in the left eye (OS). At 21 months postoperatively, the uncorrected visual acuity (UCVA) was 20 / 12.5 in both eyes. In case 2, the preoperative SE was -5.25 (OD) / -6.00 (OS). After six months, the postoperative UCVA was 20 / 12.5 in both eyes. In case 3, the preoperative SE was -4.5 (OD) / -2.0 (OS). The UCVA at the six-month follow-up was 20 / 12.5 in both eyes. No adverse events, including corneal haze, occurred in any of the patients. All three of our patients reported excellent visual outcomes following both conventional Epi-LASIK and LED, despite their histories of keloid formation. The present cases suggest that both Epi-LASIK and LED may be safe and effective techniques for myopic patients with dermatologic keloids

Modelling fragile X syndrome in rats: new directions in translational research

Fragile X syndrome (FXS) is the leading single gene cause of intellectual disability and Autism Spectrum Disorder (ASD). It is caused by epigenetic silencing of the fragile X mental retardation gene (FMR1), causing a loss of Fragile-X Mental Retardation Protein (FMRP). Over the last 2 decades, much has been learned about the pathophysiology related to the loss of FMRP from mouse models of FXS. The recent generation of a rat model of FXS opens the door to: validate phenotypes across mammalian species, address cognitive dysfunction using paradigms that are more difficult to address in mice and explore candidate therapeutics more accurately. This thesis explored the validity of a new rat model for FXS (Fmr1 KO rat). I showed that Fmr1 KO rats exhibit normal spatial navigation memory, social interactions and anxiety levels. On the contrary, when subjects were tested in a battery of spontaneous exploration tasks: object recognition (OR), object-context (OC), object-place (OP), and object-place-context (OPC) recognition, which assess associative memory, Fmr1 KO rats showed a severe deficit in remembering the most complex (episodic-like) associations. Following these results, I sought to explore the development of associative memory from postnatal day 25 (P25) to adulthood (P71). Subjects were tested in the four spontaneous exploration tasks, previously mentioned, 8 times between P25 and P71 to assess the development of their ability to discriminate novel from familiar associations between objects, contexts and places. Fmr1 KO rats’ ability to discriminate novel from familiar object-place (spatial) and object-place-context (episodic-like) associations was significantly impaired (OP was delayed, and OPC ability did not develop). In the last part of this thesis I examined whether early therapeutic intervention with lovastatin can restore the cognitive deficits I observed. Subjects were fed either a diet containing lovastatin (“lovachow”) or an identically looking control diet, between P29 and P64, and tested in the four spontaneous exploration tasks, previously mentioned. Fmr1 KO rats demonstrated a developmental profile of associative memory indistinguishable from that of WT animals. At P64, lovachow was replaced with standard laboratory chow and the animals were tested 1 and 3 months later. Surprisingly, lovastatin treated Fmr1 KO animals maintained the ability to perform the OPC task even at 3 months after the end of treatment, whereas Fmr1 KO animals on control chow showed no improvement with age. The findings of this work indicate that transgenic rats can complement existing mouse models of FXS, providing valuable insights into the effects of FMRP loss on cognitive function. Furthermore, the results from the treatment study show that not only can lovastatin treatment prevent the emergence of cognitive deficits associated with Fragile X Syndrome but also that lovastatin (and perhaps pharmaceutical interventions more generally) may prevent the developmental deficits in neuronal circuit formation which can be maintained into adulthood