Magasabbrendű talamikus magvak serkentő és gátló kontrollja = Excitatory and inhibitory control of higher order thalamic nuclei

Az OTKA pályázat során leírtunk és karakterizáltunk egy új gátlás-típust a talamuszban. E gátlórendszer axonvégződései és az általuk közvetített gátlás különbözött a talamuszban jól ismert gátlórendszerek tulajdonságaitól. Az axonterminálisok ultrastruktúrája és az általuk beidegzett célelemek hatékony gátlásra utaltak. Élettani kísérletek igazolták az anatómiai predikciókat és kimutatták, hogy ez a gátlás típus hatékony információ átvitelre képes magas frekvenciás impulzusok esetén is, mikor az ismert gátlópálya hatékonysága jelentősen csökken. Az új gátlás-típus képes megakadályozni a beidegzett talamikus sejtek működését, illetve képes kiváltani a karaterisztikus visszacsapó választ. Az új gátlás-típust sikerült azonosítani több pálya esetén, köztük főemlősökben a Parkinson-kórban érintett talamikus bemenetek esetében is. A pályázat során részletesen vizsgáltuk az új gátló pálya eredő sejtjeinek szerkezetét és működését. Egy új gátlópálya leírása, melyet egyedi működési mechanizmusok jellemeznek felveti a lehetőségét e pálya szelektív modulációjának. Olyan drogok, melyek ezen a speciális gátlóterminálison hatnak segíthetnek azon tünetek enyhítésén, melyeket e pályák aberráns aktivitása okoz (pl. Parkinson-kór, krónikus fájdalom). | During the OTKA project we discovered and characterized a novel inhibitory element in the thalamus. The structure of the nerve endings, their mode of action and the activity of the nerve cells were all different from the previously described inhibitory pathways in this brain centre. The anatomy of the nerve terminals and the nerve elements they contacted indicated powerful inhibitory action. Physiological measurements verified the anatomical predictions and demonstrated that these connections faithfully transfer inhibitory signals even at very high frequency, when the effectiveness of other inhibitory pathways is much reduced. We demonstrated that these inhibitory inputs are indeed able to silence thalamic neurons or induce strong, so-called, ?postinhibitory rebound? activity. The morhology and the actvity of the parent cells of these pathways has also been extensively characterized. We described several of these pathways in different thalamic nuclei most importantly in those known to be involved in Parkinson's disease. Discovering a separate class of inhibitory pathways in the thalamus with distinct mode of action raises the hope for their selective modulation. Drugs which acts on these terminals can help to alleviate the symptoms linked to the aberrant activity of these specialized inhibitory pathways

Optogenetic activation of septal cholinergic neurons suppresses sharp wave ripples and enhances theta oscillations in the hippocampus

Theta oscillations in the limbic system depend on the integrity of the medial septum. The different populations of medial septal neurons (cholinergic and GABAergic) are assumed to affect different aspects of theta oscillations. Using optogenetic stimulation of cholinergic neurons in ChAT-Cre mice, we investigated their effects on hippocampal local field potentials in both anesthetized and behaving mice. Cholinergic stimulation completely blocked sharp wave ripples and strongly suppressed the power of both slow oscillations (0.5-2 Hz in anesthetized, 0.5-4 Hz in behaving animals) and supratheta (6-10 Hz in anesthetized, 10-25 Hz in behaving animals) bands. The same stimulation robustly increased both the power and coherence of theta oscillations (2-6 Hz) in urethane-anesthetized mice. In behaving mice, cholinergic stimulation was less effective in the theta (4-10 Hz) band yet it also increased the ratio of theta/slow oscillation and theta coherence. The effects on gamma oscillations largely mirrored those of theta. These findings show that medial septal cholinergic activation can both enhance theta rhythm and suppress peri-theta frequency bands, allowing theta oscillations to dominate

Histological and electrophysiological evidence on the safe operation of a sharp-tip multimodal optrode during infrared neuromodulation of the rat cortex

Infrared neuromodulation is an emerging technology in neuroscience that exploits the inherent thermal sensitivity of neurons to excite or inhibit cellular activity. Since there is limited information on the physiological response of intracortical cell population in vivo including evidence on cell damage, we aimed to create and to validate the safe operation of a microscale sharp-tip implantable optrode that can be used to suppress the activity of neuronal population with low optical power continuous wave irradiation. Effective thermal cross-section and electric properties of the multimodal microdevice was characterized in bench-top tests. The evoked multi-unit activity was monitored in the rat somatosensory cortex, and using NeuN immunocytochemistry method, quantitative analysis of neuronal density changes due to the stimulation trials was evaluated. The sharp tip implant was effectively used to suppress the firing rate of neuronal populations. Histological staining showed that neither the probe insertion nor the heating protocols alone lead to significant changes in cell density in the close vicinity of the implant with respect to the intact control region. Our study shows that intracortical stimulation with continuous-wave infrared light at 1550 nm using a sharp tip implantable optical microdevice is a safe approach to modulate the firing rate of neurons

Infrared neural stimulation and inhibition using an implantable silicon photonic microdevice

Brain is one of the most temperature sensitive organs. Besides the fundamental role of temperature in cellular metabolism, thermal response of neuronal populations is also significant during the evolution of various neurodegenerative diseases. For such critical environmental factor, thorough mapping of cellular response to variations in temperature is desired in the living brain. So far, limited efforts have been made to create complex devices that are able to modulate temperature, and concurrently record multiple features of the stimulated region. In our work, the in vivo application of a multimodal photonic neural probe is demonstrated. Optical, thermal, and electrophysiological functions are monolithically integrated in a single device. The system facilitates spatial and temporal control of temperature distribution at high precision in the deep brain tissue through an embedded infrared waveguide, while it provides recording of the artefact-free electrical response of individual cells at multiple locations along the probe shaft. Spatial distribution of the optically induced temperature changes is evaluated through in vitro measurements and a validated multi-physical model. The operation of the multimodal microdevice is demonstrated in the rat neocortex and in the hippocampus to increase or suppress firing rate of stimulated neurons in a reversible manner using continuous wave infrared light (λ = 1550 nm). Our approach is envisioned to be a promising candidate as an advanced experimental toolset to reveal thermally evoked responses in the deep neural tissue

Dynamics of sleep oscillations is coupled to brain temperature on multiple scales

Sleep spindle frequency positively, duration negatively correlates with brain temperature. Local heating of the thalamus produces similar effects in the heated area. Thalamic network model corroborates temperature dependence of sleep spindle frequency. Brain temperature shows spontaneous microfluctuations during both anesthesia and natural sleep. Larger fluctuations are associated with epochs of REM sleep. Smaller fluctuations correspond to the alteration of spindling and delta epochs of infra-slow oscillation.Every form of neural activity depends on temperature, yet its relationship to brain rhythms is poorly understood. In this work we examined how sleep spindles are influenced by changing brain temperatures and how brain temperature is influenced by sleep oscillations. We employed a novel thermoelectrode designed for measuring temperature while recording neural activity. We found that spindle frequency is positively correlated and duration negatively correlated with brain temperature. Local heating of the thalamus replicated the temperature dependence of spindle parameters in the heated area only, suggesting biophysical rather than global modulatory mechanisms, a finding also supported by a thalamic network model. Finally, we show that switches between oscillatory states also influence brain temperature on a shorter and smaller scale. Epochs of paradoxical sleep as well as the infra-slow oscillation were associated with brain temperature fluctuations below 0.2°C. Our results highlight that brain temperature is massively intertwined with sleep oscillations on various time scales