Mechanisms affecting the temporal characteristics of retinal ganglion cell light responses: a study of transiency and oscillatory activity in the mammalian retina

Hagyományos érzékeink közül kétségtelenül a látás az, amelyre egy átlagember leginkább támaszkodik a mindennapok során, látórendszerünk működése éppen ezért hosszú ideje foglalkoztatja a tudományt. Régóta ismert, hogy az általunk vizsgált dúcsejtek adekvát fénystimulusra két specifikus időbeli karakterisztikával reagálnak (Werblin és Downling 1969; Kaneko 1970): bizonyos esetekben a fényválasz gyors, az akciós potenciálok száma hirtelen emelkedik és a csúcsaktivitás elérése után szintén gyors ütemben csökken (tranziens válasz), más esetekben azonban a sejt akár stimulus teljes ideje alatt fenntarthatja elektromos aktivitását (fenntartott válasz). A tranziens/fenntartott kettősség kialakulási mechanizmusa azonban jelenleg még nem tisztázott. A dolgozat elsődleges célja volt tehát a retinális dúcsejtek tranzienciájának vizsgálata. Munkánk során négy különböző számítási módszert hasonlítottunk össze, célunk egy megbízható és széles körben alkalmazható módszer megalkotása volt a tranziencia, mint karakterisztika számosítására. Úgy gondoljuk, az általunk PSTHτ néven jegyzett módszer, mely egyedülálló módon lehetővé tesz a dúcsejtek tranzienciájának összehasonlítását a bipoláris sejteken mért lassú potenciálokkal is (PSTHτ vs tau, mint időkonstans), megfelel a megbízhatóság és alkalmazhatóság szintjén támasztott elvárásainknak. Kísérletes eredményeink ugyanakkor arra engednek következtetni, hogy az ismert tranziens/fenntartott kettőség a dúcsejtek szintjén a feltételezettnél lényegesen összetettebb formában nyilvánul meg, ezért indokoltnak látjuk egy harmadik, korábban nem jegyzett átmeneti/köztes kategória bevezetését. Nem jelölhetünk ki továbbá egyértelmű meghatározó tényezőt a dúcsejt-tranziencia mögött: kutatómunkánk végkövetkeztetése, hogy az egyéni szabályozó mechanizmusokkal szemben a tranzienciát a dúcsejtre érkező bemenetek (vertikális parallel pályák és laterális inhibíció) együttesen és típus-specifikusan határozzák meg. A fényválasz kinetikáját tekintve vizsgáltuk még munkánk során a dúcsejtek oszcillációs aktivitását. Bár OFF válaszok szintjén az oszcillációt az egér retinában nem sikerült kimutatnunk, az ON válaszokat tekintve kijelenthetjük, hogy az oszcillációs mintázat kialakításért elsősorban az amakrin sejtek által létrehozott laterális hatások felelősek, ugyanakkor a retina különböző pontjaira kiterjedő szinkronizációt az elektromos szinapszisok hozzák létre

Connexin36 Expression in the Mammalian Retina: A Multiple-Species Comparison

Much knowledge about interconnection of human retinal neurons is inferred from results on animal models. Likewise, there is a lack of information on human retinal electrical synapses/gap junctions (GJ). Connexin36 (Cx36) forms GJs in both the inner and outer plexiform layers (IPL and OPL) in most species including humans. However, a comparison of Cx36 GJ distribution in retinas of humans and popular animal models has not been presented. To this end a multiple-species comparison was performed in retinas of 12 mammals including humans to survey the Cx36 distribution. Areas of retinal specializations were avoided (e.g., fovea, visual streak, area centralis), thus observed Cx36 distribution differences were not attributed to these species-specific architecture of central retinal areas. Cx36 was expressed in both synaptic layers in all examined retinas. Cx36 plaques displayed an inhomogenous IPL distribution favoring the ON sublamina, however, this feature was more pronounced in the human, swine and guinea pig while it was less obvious in the rabbit, squirrel monkey, and ferret retinas. In contrast to the relative conservative Cx36 distribution in the IPL, the labels in the OPL varied considerably among mammals. In general, OPL plaques were rare and rather small in rod dominant carnivores and rodents, whereas the human and the cone rich guinea pig retinas displayed robust Cx36 labels. This survey presented that the human retina displayed two characteristic features, a pronounced ON dominance of Cx36 plaques in the IPL and prevalent Cx36 plaque conglomerates in the OPL. While many species showed either of these features, only the guinea pig retina shared both. The observed similarities and subtle differences in Cx36 plaque distribution across mammals do not correspond to evolutionary distances but may reflect accomodation to lifestyles of examined species

Expression of Ca²⁺-Binding Buffer Proteins in the Human and Mouse Retinal Neurons

Ca2+-binding buffer proteins (CaBPs) are widely expressed by various neurons throughout the central nervous system (CNS), including the retina. While the expression of CaBPs by photoreceptors, retinal interneurons and the output ganglion cells in the mammalian retina has been extensively studied, a general description is still missing due to the differences between species, developmental expression patterns and study-to-study discrepancies. Furthermore, CaBPs are occasionally located in a compartment-specific manner and two or more CaBPs can be expressed by the same neuron, thereby sharing the labor of Ca2+ buffering in the intracellular milieu. This article reviews this topic by providing a framework on CaBP functional expression by neurons of the mammalian retina with an emphasis on human and mouse retinas and the three most abundant and extensively studied buffer proteins: parvalbumin, calretinin and calbindin

Transience of the Retinal Output Is Determined by a Great Variety of Circuit Elements

Retinal ganglion cells (RGCs) encrypt stimulus features of the visual scene in action potentials and convey them toward higher visual centers in the brain. Although there are many visual features to encode, our recent understanding is that the ~46 different functional subtypes of RGCs in the retina share this task. In this scheme, each RGC subtype establishes a separate, parallel signaling route for a specific visual feature (e.g., contrast, the direction of motion, luminosity), through which information is conveyed. The efficiency of encoding depends on several factors, including signal strength, adaptational levels, and the actual efficacy of the underlying retinal microcircuits. Upon collecting inputs across their respective receptive field, RGCs perform further analysis (e.g., summation, subtraction, weighting) before they generate the final output spike train, which itself is characterized by multiple different features, such as the number of spikes, the inter-spike intervals, response delay, and the rundown time (transience) of the response. These specific kinetic features are essential for target postsynaptic neurons in the brain in order to effectively decode and interpret signals, thereby forming visual perception. We review recent knowledge regarding circuit elements of the mammalian retina that participate in shaping RGC response transience for optimal visual signaling

Obtaining PSTHτ transiency values in this study.

<p><b>(A).</b> Extracellular spike recordings (middle trace) were detected upon photopic light stimuli (bottom trace). Spikes were sorted offline by using the appropriate threshold line (dashed line) to determine spike timestamps (top trace). <b>(B).</b> To quantify transiency, peristimulus time histograms were created upon light response timestamps using the light onset as reference. PSTHτ values were obtained by determining the peak time (t_peak) and the peak amplitude (A1) and then A1*1/e was calculated and that gave the time constant itself (τ).</p

Comparison of PTSHτ and slow potential τ values.

<p><b>(A).</b> Intracellular recording from an ON center RGC in the mouse retina that displays both slow potentials and spikes (upper trace). Spikes (second trace) and slow potentials (lower two traces) were obtained from the same recording by applying either a high-pass (>100 Hz) or a low-pass filter (<50 and 100 Hz for the third and fourth traces), respectively. Spike trains and slow potentials were then utilized to calculate both PTSHτ and τ values for the same light responses. <b>(B).</b> Bar-graph shows PTSHτ and τ triplets for randomly selected RGCs. In each column PTSHτ and τ values appeared comparable for the tested cells.</p

PSTHτ values depict the stimulus dependency of RGC responses.

<p><b>(A).</b> Selected RGC (n = 6) PSTHτ values obtained upon full-field light evoked responses were stable (cells 1, 2, 5 and 6) while those of others (cells 3 and 4) displayed some intensity dependent change. <b>(B).</b> PSTHτ values of selected RGCs (n = 4) were obtained by a series of light spots with varying diameters (10, 20, 40, 60, 80, 140, 180, 270 and 360 μm). RGC PSTHτ values change according to the size of the presented stimulus. <b>(C).</b> Histogram is showing PSTHτ values for RGC (n = 6) responses. PSTHτ values were calculated for PSTHs obtained with different bin sizes (10, 20 and 30 ms) for each cell.</p