Tonically Active Kainate Receptors (tKARs) : A Novel Mechanism Regulating Neuronal Function in the Brain

Fast excitatory transmission between neurons in the central nervous system is mainly mediated by L-glutamate acting on ligand gated (ionotropic) receptors. These are further categorized according to their pharmacological properties to AMPA (2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid), NMDA (N-Methyl-D-aspartic acid) and kainate (KAR) subclasses. In the rat and the mouse hippocampus, development of glutamatergic transmission is most dynamic during the first postnatal weeks. This coincides with the declining developmental expression of the GluK1 subunit-containing KARs. However, the function of KARs during early development of the brain is poorly understood. The present study reveals novel types of tonically active KARs (hereafter referred to as tKARs) which play a central role in functional development of the hippocampal CA3-CA1 network. The study shows for the first time how concomitant pre- and postsynaptic KAR function contributes to development of CA3-CA1 circuitry by regulating transmitter release and interneuron excitability. Moreover, the tKAR-dependent regulation of transmitter release provides a novel mechanism for silencing and unsilencing early synapses and thus shaping the early synaptic connectivity. The role of GluK1-containing KARs was studied in area CA3 of the neonatal hippocampus. The data demonstrate that presynaptic KARs in excitatory synapses to both pyramidal cells and interneurons are tonically activated by ambient glutamate and that they regulate glutamate release differentially, depending on target cell type. At synapses to pyramidal cells these tKARs inhibit glutamate release in a G-protein dependent manner but in contrast, at synapses to interneurons, tKARs facilitate glutamate release. On the network level these mechanisms act together upregulating activity of GABAergic microcircuits and promoting endogenous hippocampal network oscillations. By virtue of this, tKARs are likely to have an instrumental role in the functional development of the hippocampal circuitry. The next step was to investigate the role of GluK1 -containing receptors in the regulation of interneuron excitability. The spontaneous firing of interneurons in the CA3 stratum lucidum is markedly decreased during development. The shift involves tKARs that inhibit medium-duration afterhyperpolarization (mAHP) in these neurons during the first postnatal week. This promotes burst spiking of interneurons and thereby increases GABAergic activity in the network synergistically with the tKAR-mediated facilitation of their excitatory drive. During development the amplitude of evoked medium afterhyperpolarizing current (ImAHP) is dramatically increased due to decoupling tKAR activation and ImAHP modulation. These changes take place at the same time when the endogeneous network oscillations disappear. These tKAR-driven mechanisms in the CA3 area regulate both GABAergic and glutamatergic transmission and thus gate the feedforward excitatory drive to the area CA1. Here presynaptic tKARs to CA1 pyramidal cells suppress glutamate release and enable strong facilitation in response to high-frequency input. Therefore, CA1 synapses are finely tuned to high-frequency transmission; an activity pattern that is common in neonatal CA3-CA1 circuitry both in vivo and in vitro. The tKAR-regulated release probability acts as a novel presynaptic silencing mechanism that can be unsilenced in response to Hebbian activity. The present results shed new light on the mechanisms modulating the early network activity that paves the way for oscillations lying behind cognitive tasks such as learning and memory. Kainate receptor antagonists are already being developed for therapeutic use for instance against pain and migraine. Because of these modulatory actions, tKARs also represent an attractive candidate for therapeutic treatment of developmentally related complications such as learning disabilities.

Valokuvallistettu luonto : I. K. Inhan tuotanto luonnon merkityksellistäjänä

Photographized nature I. K. Inha s work as a signification of nature The dissertation examines, through the work of the Finnish photographer and writer I. K. Inha (formerly Konrad Into Nyström) (1865 1930), the different ways in which the signification of nature is achieved. The principal material consists of Inha s work from 1890 to 1925, from which a number of photographs and texts are considered and upon which the photographization of nature is contemplated. The dissertation addresses the issue of how nature is conceived and how the act of photographizing it can be defined. The methodical context of the study is composed of three thematic baskets that structure the material and which consist of narrations on Finnish national perception, nature conservation and understanding the world. In the first case nature is seen as the natural environment encompassing lakes, seashores, forests, and hills, which at the time were often perceived from a utilitarian viewpoint. By the photographization they generated a pictorial narrative that could be shared. The natural environment was thus turned into landscape by means of photography, following the global pictorial concepts picturesque and sublime, as well as the national canons that had been developed in literature and the visual arts. In the narrations concerning nature conservation, the photographization did not merely occur within the limits of presuppositions, but rather nature was given the opportunity to unfold itself. While the photograph was being established as a basis for supporting nature conservation or to highlight the destruction of nature at the hand of Man, an attempt was made to represent subjects that were difficult to convey in photographs, such as nature s power or the miracle of growth. The thesis suggests, that in the third case the concept of nature broke away from its strict interconnection with the natural environment and led to a contemplation of nature that is perceivable in a person. In this context the photograph and the photographization are interpreted as an attempt to understand a person and his or her very existence in the world, while this same existential wonder is seen as being embodied in Inha s portrait of a rune singer and in his photographs of forest interior and water. Further, the thesis asks whether photographing nature could be interpreted as an action similar to the idea of the phenomenological reduction as a means of bypassing the photographer s prevailing way of being.

Myymälämarkkinointi osana markkinointiviestintää – Kuluttajien arvostamat tekijät päivittäistavarakaupassa. CASE: K-supermarket Torpparinmäki

Tässä tutkimuksessa tarkastellaan K-supermarket Torpparinmäen asiakkaiden arvostuksia myymälän sisäisiin toimiin liittyen. Myymälän sisäisiin toimiin lasketaan tässä tutkimuksessa kuuluvan laaja kirjo asioita kuten hinnat, tarjoukset, valikoiman laajuus eri tuoteryhmissä, elämyksellisyys, hyllysijoittelu, kaupan selkeys, asiakaspalvelu sekä viihtyisyys. Myös merkityksellisten ja vähemmän merkityksellisten asioiden toteutumisesta kyseisessä myymälässä halutaan vastauksia. Tutkimuksessa nostetaan esille myös erilaiset tiedotuskanavat kaupan markkinoinnissa. Tämän lisäksi sivutaan aihetta kuluttajien päivittäistavarakaupan valintakriteereistä. Tutkimusote on kvantitatiivinen ja kysely suoritettiin survey-tutkimuksena. Tutkimuksessa haluttiin tämän lisäksi kerätä mahdollisimman paljon myös avoimia kommentteja sekä myymälästä että päivittäistavarakaupan valintaan liittyvistä kriteereistä. K-supermarket Torpparinmäen pahin kilpailija alueellaan on S-market Torpparinmäki. Asiakkailta haluttiin kysyä avoimesti, miksi asioivat juuri kyseisessä myymälässä. Kysely suoritettiin lauantaipäivänä K-supermarket Torpparinmässä asioineille 18-89-vuotiaille henkilöille. Kyselyyn vastasi 80 asiakasta, joista 65 % oli naisia ja 35 % miehiä. Tutkimuksen viitekehys jakaa myymälämarkkinoinnin neljään pääkategoriaan: viihtyvyystekijä, palvelutekijä, hintatekijä sekä valikoimatekijä. Näiden tekijöiden merkityksiä asiakkaille haluttiin tutkimuksessa asettaa tärkeysjärjestykseen. Myös näiden tekijöiden toteumaa K-supermarket Torpparinmäessä haluttiin selvittää. Tulosten analysoinnin perusteella edellä mainituista pääkategorioista tärkeimmäksi muodostui valikoimatekijä. Valikoimien monipuolisuutta pidettiin kaikista tärkeimpänä tekijänä myymälässä. Myös luomu- ja lähiruoan valikoimia pidettiin tärkeäpänä kuin valmisruokien. Toiseksi eniten asiakkaat arvostivat asiakaspalvelua ja vasta kolmannelle sijalle päätyi hintatekijä. Neljänneksi tärkeimpänä asiakkaat pitivät viihtyvyystekijää. Mikään tekijöistä ei erottunut suuresti toisistaan, mutta erot olivat kuitenkin selkeitä.