Projekcja oreksynowa (hipokretynowa) nowym układem niespecyficznym mózgowia ssaków

Odkrycie w okolicach podwzgórza ssaków w końcu lat 90. ubiegłego wieku neuropeptydu oreksyny (hipokretyny) dało nowe spojrzenie na układy niespecyficzne mózgowia. Okazało się bowiem, że neurony oreksynowe posiadają rozsianą, dyfuzyjną projekcję do wielu bardzo ważnych obszarów mózgowia, w tym przede wszystkim do głównych źródeł klasycznej projekcji niespecyficznej zlokalizowanej w pniu mózgu. Dalsze badania wykazały, że projekcja oreksynowa jes t nadrzędna i reguluje aktywność neuronów cholinergicznych, noradrenergicznych, dopaminergicznych, histaminergicznych i serotninergicznych, stając się tym samym podstawową w reakcji wzbudzenia mózgowia (arousal). Główna rola, tego nowo odkrytego układu niespecyficznego mózgowia polega na regulacji najważniejszego i podstawowego rytmu naszego ciała - snu i czuwania. Istnieją wstępne doniesienia sugerujące obecność włókien neuronów oreksynowych w okolicach jąder nadskrzyżowaniowych podwzgórza i listka ciała kolankowatego bocznego wzgórza, dwu głównych elementach neuronalnego mechanizmu zegara biologicznego ssaków. Odkrycie neuropeptydu oreksynowgo jego kliniczne i biologiczne znaczenie to kolejny krok milowy w neurobiologii.Zadanie pt. „Digitalizacja i udostępnienie w Cyfrowym Repozytorium Uniwersytetu Łódzkiego kolekcji czasopism naukowych wydawanych przez Uniwersytet Łódzki” nr 885/P-DUN/2014 dofinansowane zostało ze środków MNiSW w ramach działalności upowszechniającej naukę

Light-Induced Responses of Slow Oscillatory Neurons of the Rat Olivary Pretectal Nucleus

Background: The olivary pretectal nucleus (OPN) is a small midbrain structure responsible for pupil constriction in response to eye illumination. Previous electrophysiological studies have shown that OPN neurons code light intensity levels and therefore are called luminance detectors. Recently, we described an additional population of OPN neurons, characterized by a slow rhythmic pattern of action potentials in light-on conditions. Rhythmic patterns generated by these cells last for a period of approximately 2 minutes. Methodology: To answer whether oscillatory OPN cells are light responsive and whether oscillatory activity depends on retinal afferents, we performed in vivo electrophysiology experiments on urethane anaesthetized Wistar rats. Extracellular recordings were combined with changes in light conditions (light-dark-light transitions), brief light stimulations of the contralateral eye (diverse illuminances) or intraocular injections of tetrodotoxin (TTX). Conclusions: We found that oscillatory neurons were able to fire rhythmically in darkness and were responsive to eye illumination in a manner resembling that of luminance detectors. Their firing rate increased together with the strength of the light stimulation. In addition, during the train of light pulses, we observed two profiles of responses: oscillationpreserving and oscillation-disrupting, which occurred during low- and high-illuminance stimuli presentation respectively. Moreover, we have shown that contralateral retina inactivation eliminated oscillation and significantly reduced the firin

Circadian Clock and Nutrition

Rhythmicity is a fundamental characteristic of every living organism [...

Repeated measures factorial ANOVA analysis of oscillatory neurons responses to light flashes of different intensities.

<p>(<b>A</b>) Average firing rates during peri-stimulation times of different light intensities (indicated on <i>x</i>-axis). Repeated measures factorial ANOVA analysis revealed a highly significant effect of light on neuronal firing (n = 11; <i>p</i><0.00001; <i>F</i> = 223.18; Tukey post hoc test; * <i>p</i><0.05, ***<i>p</i><0.001, ^###<i>p</i><0.00005) and strong interaction between the state and light intensities (<i>p</i><0.00001, <i>F</i> = 12.38). (<b>B</b>) The average sum of spikes generated during the response and (<b>C</b>) average maximal amplitude of the transient component of recorded responses to different illumination strength calculated from PSTHs and plotted on semi-logarithmic scale. Note the nearly linear relationship between obtained averages and log of light intensity. Dashed line corresponds to trend-line.</p

Responses of oscillatory OPN cell to white light pulses of different intensities.

<p>Recordings were taken from the right OPN and when oscillatory cell was encountered contralateral eye was stimulated with light pulses of different intensity delivered with white light-emitting diode. Each stimulus lasted for 3 s and given light intensity was presented 10 times at 20 s interval. (<b>A–G</b>) Raster displays (top) and peri-stimulus time histograms (bottom) generated for one recorded cell. Each dash in the raster plot corresponds to an action potential and each row to a trial. Trials are time-locked with respect to the onset of stimulus (indicated by time = 0) and stimulus latency is marked with dashed blue line. The activity (summed across all trials of raster display) is shown as frequency histograms, in 100 ms bin width. In the left upper corner of each PSTH light intensity that was used during stimulation is indicated. Note that amplitude of the response increase together with stimulus intensity. (<b>H</b>) A composite average PSTH constructed from composite PSTHs obtained for individual light intensity stimulations across all analyzed cells (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033083#pone.0033083.s002" target="_blank">Fig. S2</a>); the <i>x</i>-axis denotes peri-stimulation time, the <i>y</i>-axis stimulus strength and neuronal firing (100 ms bin width) is colour-coded (inset on the right side).</p

Effects of light-dark-light transitions on oscillatory activity in the OPN neurons.

<p>(<b>A</b>) Firing rate histogram of a multi-unit recording of OPN oscillatory cells under light-on and light-off conditions. Period of darkness is indicated by black rectangle. Numbers (<b>1</b>, <b>2</b> and <b>3</b>) above the histogram correspond to the baseline light, darkness and recovery of light conditions respectively. (<b>B</b>) Average firing rates (per second) and (<b>C</b>) mean period of oscillation during different stages. After turning off the light firing rate decreased, however not significantly (n = 14; <i>p</i> = 0.27; <i>F</i> = 1.33) and the period lengthened after dark-to-light transition (<i>p</i> = 0.2; <i>F</i> = 1.64). Note, that dark-light transition caused transient disruption of the oscillations.</p

A schematic representation of the modulatory effect of light conditions on oscillatory activities in visual system structures.

<p>The coloured drawing illustrates reciprocal connections between the OPN, SCN, LGN and IGL and their innervations originating in the retina. Black and white schemes show slow oscillatory modes of firing and its dependence on light in the OPN (<b>A</b>), SCN (<b>B</b>), LGN (<b>C</b>) and IGL (<b>D</b>). Amplitude of the peaks corresponds to activity level and width of the peaks reflects period of oscillations. Light conditions are indicated with rectangles below the schemes: white rectangles correspond to periods of light, black rectangles correspond to darkness. As explained in the text, our assumption is that SOA in the OPN are driven by the retinal excitatory input. Our previous results showed that oscillations in the OPN persist in presence of GABAergic antagonist and therefore, they can not be driven by SCN or IGL neurons, which are GABAergic. On the contrary, the LGN projections are glutamatergic and indirectly convey retinal information to the OPN. Based on the fact that SOA in the LGN occur only in darkness (<b>B</b>) it is rather unlikely that LGN drives the rhythm in the OPN because occurrence of the latter one does not depend on the light conditions (<b>A</b>).</p

Response profiles of oscillatory cell to a train of light stimuli.

<p>(<b>A</b>, <b>B</b>) Firing rate histograms of oscillatory OPN neuron during train stimulation with 3 second long light flashes (•).Grey dashed sinusoid lines superimposed on histograms reflect baseline oscillation periods. (<b>A</b>) The oscillation-preserving response profile was characterized by low responsiveness during active phase of oscillatory cycle and marked augmentation of activity during silent phase of oscillation. Occurrence of this profile was associated with low-intensity light stimulations and does not interrupted slow oscillatory pattern. The oscillation-disrupting response profile (<b>B</b>) was characterized by similar responsiveness to each stimulus and was apparent at high-intensity light stimulations. Spectral analysis of the 260 second long segment of the histogram (marked with blue dashed line) using FFT algorithm confirmed oscillation-preserving (<b>C</b>) or oscillation-disrupting (<b>D</b>) modes of response. Note that the peak location in <b>C</b> (115 s) correspond to observed period of oscillation. Plot <b>D</b> is lacking the peak at a similar location but instead significant periodicity was detected at 20 second (indicated by an arrow), matching rhythmicity of the stimulation and reflecting responses of the cell. (<b>E</b> and <b>F</b>) individual light-induced activity changes calculated from respective activity histograms and measured as a number of spikes generated during 3 seconds preceding a stimulus (1) and during a light flash (2). Note that activity changes plotted in <b>E</b> are not consistent and when high baseline activity takes place, the response is dampened (red lines).</p

The effect of intraocular injections of TTX on slow oscillatory activities in the OPN.

<p>Firing rate histograms of simultaneous recordings of multiunit oscillatory activities in right (OPN(R), <b>A</b>) and left (OPN(L), <b>B</b>) OPN. After recording baseline activity intravitreal injections (10 µl/eye) of tetrodotoxin were performed. TTX(I) and TTX(C) on the inset graphs denotes injection to ipsilateral and contralateral eye respectively. Note that blockage of contralateral retina (relative to recording site) caused pronounced decrease in firing rate in addition to disappearance of rhythmic spike generation. If contralateral eye was intact, inactivation of ipsilateral retina did not disturb oscillatory pattern. Insets on each plot shows mean ± S.E.M. and results of one-way ANOVA tests (for <b>A</b>: n = 12; <i>p</i> = 0.0004; <i>F</i> = 9.85; for <b>B</b>: n = 9; <i>p</i> = 0.00001; <i>F</i> = 18.19; Tukey post hoc tests; *** <i>p</i><0.001).</p