Karolina Szokol

Publications of Karolina Szokol

• Organization of functional synaptic connections between medullary reticulospinal neurons and lumbar descending commissural interneurons in the neonatal mouse.

  Authors: Karolina Szokol, Joel C Glover, Marie-Claude Perreault

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 03/2011; 31(12):4731-42.

  The medullary reticular formation (MRF) of the neonatal mouse is organized so that the medial and lateral MRF activate hindlimb and trunk motoneurons (MNs) with differential predominance. The goal ofThe medullary reticular formation (MRF) of the neonatal mouse is organized so that the medial and lateral MRF activate hindlimb and trunk motoneurons (MNs) with differential predominance. The goal of the present study was to investigate whether this activation is polysynaptic and mediated by commissural interneurons with descending axons (dCINs) in the lumbar spinal cord. To this end, we tested the polysynapticity of inputs from the MRF to MNs and tested for the presence of selective inputs from medial and lateral MRF to 574 individual dCINs in the L2 segment of the neonatal mouse. Reticulospinal-mediated postsynaptic Ca(2+) responses in MNs were reduced in the presence of mephenesin and after a midline lesion, suggesting the involvement of dCINs in mediating the responses. Consistent with this, stimulation of reticulospinal neurons in the medial or lateral MRF activated 51% and 57% of ipsilateral dCINs examined (255 and 352 dCINs, respectively) and 52% and 46% of contralateral dCINs examined (166 and 133 dCINs, respectively). The proportion of dCINs that responded specifically to stimulation of medial or lateral MRF was similar to the proportions of dCINs that responded to both MRF regions or to neither. The three responsive dCIN populations had largely overlapping spatial distributions. We demonstrate the existence of dCIN subpopulations sufficient to mediate responses in lumbar motoneurons from reticulospinal pathways originating from the medial and lateral MRF. Differential control of trunk and hindlimb muscles by the medullary reticulospinal system may therefore be mediated in part by identifiable dCIN populations.

• Imaging synaptically mediated responses produced by brainstem inputs onto identified spinal neurons in the neonatal mouse.

  Authors: Karolina Szokol, Marie-Claude Perreault

  Journal of neuroscience methods. 06/2009; 180(1):1-8.

  Descending inputs to spinal cord neurons in mammals have previously been characterized functionally using microelectrode recording of single neurons, a technique with high spatial and temporalDescending inputs to spinal cord neurons in mammals have previously been characterized functionally using microelectrode recording of single neurons, a technique with high spatial and temporal resolution but low yield. Consequently our knowledge about the functional connections between the brain and the spinal cord has been accumulating at a very low pace. Here we describe a high throughput optical recording approach in an ex vivo brainstem-spinal cord preparation of the neonatal mouse that permits screening many spinal neurons simultaneously for synaptic inputs from descending axons. The fluorescent calcium indicator calcium green dextran amine was loaded retrogradely into specific spinal neuron populations, including motoneurons (MNs) of the medial and lateral motor columns and two populations of interneurons with descending axons (dINs) in the ventral funiculus. Focal electrical stimulation of brainstem neuron populations with descending axons generated synaptic responses revealed by transient increases in intracellular calcium concentration in all four populations of spinal neurons. The resultant fluorescence signals could be readily visualized in individual MNs directly through the ventral white matter. In the more deeply located dINs, responses could be readily visualized in individual neurons from the surface of an oblique cut through the spinal cord. The rapid optical investigation of functional connections between brainstem descending neurons and various populations of spinal neurons in the living mammalian preparation should help uncover some of the key features of supraspinal sensory and motor control and provide a valuable tool for examining the re-innervation of spinal neurons by descending axons after spinal cord regeneration.

• Differential origin of reticulospinal drive to motoneurons innervating trunk and hindlimb muscles in the mouse revealed by optical recording.

  Authors: Karolina Szokol, Joel Clinton Glover, Marie-Claude Perreault

  The Journal of physiology. 10/2008;

  To better understand how the brainstem reticular formation controls and coordinates trunk and hindlimb muscle activity, we used optical recording to characterize the functional connections betweenTo better understand how the brainstem reticular formation controls and coordinates trunk and hindlimb muscle activity, we used optical recording to characterize the functional connections between medullary reticulospinal neurons and lumbar motoneurons of the L2 segment in the neonatal mouse. In an isolated brain stem-spinal cord preparation, synaptically induced calcium transients were visualized in individual MNs of the ipsilateral and contralateral medial and lateral motor columns (MMC, LMC) following focal electrical stimulation of the medullary reticular formation (MRF). Stimulation of the MRF elicited differential responses in MMC and LMC, according to a specific spatial organization. Stimulation of the medial MRF elicited responses predominantly in the LMC whereas stimulation of the lateral MRF elicited responses predominantly in the MMC. This reciprocal response pattern was observed on both the ipsilateral and contralateral sides of the spinal cord. To ascertain whether the regions stimulated contained reticulospinal neurons, we retrogradely labeled MRF neurons with axons coursing in different spinal funiculi, and compared the distributions of the labeled neurons to the stimulation sites. We found a large number of retrogradely labeled neurons within regions of the gigantocellularis reticular nucleus (including its pars ventralis and alpha) where most stimulation sites were located. The existence of a mediolateral organization within the MRF, whereby distinct populations of reticulospinal neurons predominantly influence medial or lateral motoneurons, provides an anatomical substrate for the differential control of trunk and hindlimb muscles. Such an organization introduces flexibility in the initiation and coordination of activity in the two sets of muscles that would satisfy many of the functional requirements that arise during postural and non-postural motor control in mammals.

• Ionic basis of tonic firing in spinal substantia gelatinosa neurons of rat.

  Authors: Igor V Melnick, Sónia F A Santos, Karolina Szokol, Péter Szûcs, Boris V Safronov

  Journal of neurophysiology. 03/2004; 91(2):646-55.

  Ionic conductances underlying excitability in tonically firing neurons (TFNs) from substantia gelatinosa (SG) were studied by the patch-clamp method in rat spinal cord slices. Ca(2+)-dependent K(+)Ionic conductances underlying excitability in tonically firing neurons (TFNs) from substantia gelatinosa (SG) were studied by the patch-clamp method in rat spinal cord slices. Ca(2+)-dependent K(+) (K(CA)) conductance sensitive to apamin was found to prolong the interspike intervals and stabilize firing evoked by a sustained membrane depolarization. Suppression of Ca(2+) and K(CA) currents, however, did not abolish the basic pattern of tonic firing, indicating that it was generated by voltage-gated Na(+) and K(+) currents. Na(+) and K(+) channels were further analyzed in somatic nucleated patches. Na(+) channels exhibited fast activation and inactivation kinetics and followed two-exponential time course of recovery from inactivation. The major K(+) current was carried through tetraethylammonium (TEA)-sensitive rapidly activating delayed-rectifier (K(DR)) channels with a slow inactivation. The TEA-insensitive transient A-type K(+) (K(A)) current was very small in patches and was strongly inactivated at resting potential. Block of K(DR) rather than K(A) conductance by 1 mM TEA lowered the frequency and stability of firing. Intracellular staining with biocytin revealed at least three morphological groups of TFNs. Finally, on the basis of present data, we created a model of TFN and showed that Na(+) and K(DR) currents are sufficient to generate a basic pattern of tonic firing. It is concluded that the balanced contribution of all ionic conductances described here is important for generation and modulation of tonic firing in SG neurons.

• Neurons with distinctive firing patterns, morphology and distribution in laminae V-VII of the neonatal rat lumbar spinal cord.

  Authors: Péter Szûcs, Francis Odeh, Karolina Szokol, Miklós Antal

  The European journal of neuroscience. 03/2003; 17(3):537-44.

  It is generally accepted that neurons in the ventral spinal grey matter, a substantial proportion of which can be regarded as constituents of the spinal motor apparatus, receive and integrateIt is generally accepted that neurons in the ventral spinal grey matter, a substantial proportion of which can be regarded as constituents of the spinal motor apparatus, receive and integrate synaptic inputs arising from various peripheral, spinal and supraspinal sources. Thus, a profound knowledge concerning the integrative properties of interneurons in the spinal ventral grey matter appears to be essential for a fair understanding of operational principles of spinal motor neural assemblies. Using the whole cell patch clamp configuration in a correlative physiological and morphological experimental approach, here we demonstrate that the intrinsic membrane properties of neurons vary widely in laminae V-VII of the ventral grey matter of the neonatal rat lumbar spinal cord. Based on their firing patterns in response to depolarizing current steps, we have classified the recorded neurons into four categories: 'phasic', 'repetitive', 'single' and 'slow'. Neurons with firing properties characteristic of the 'phasic', 'repetitive' and 'single' cells have previously been reported also in the superficial and deep spinal dorsal horn, but this is the first account in the literature in which 'slow' neurons have been recovered and described in the spinal cord. The physiological heterogeneity in conjunction with the morphological correlation and distribution of neurons argues that different components of motor neural assemblies in the spinal ventral grey matter possess different signal processing characteristics.

• Gerincvelői neuronhálózatok szerveződése, pre- és posztnatális fejlődése, és plasztikus változásai neuropátiás és gyulladásos fájdalom modellekben = Organization, pre- and postnatal development of spinal neural circuits, and their plasticity in neuropathic and inflammatory pain states

  Authors: Miklós Antal, Mária Eördögh, Dóra Muszil, Ildikó Papp, Mihály Petkó, Zoltán Szabó, Karolina Szokol, Péter Szűcs, Gábor Veress

  A pályázat célul tűzte ki a gerincvelői nociceptív ingerületfeldolgozást végző és a gerincvelői szintű motoros működéseket irányító neuronhálózatok szerveződésének, kémiai tulajdonságainak, ésA pályázat célul tűzte ki a gerincvelői nociceptív ingerületfeldolgozást végző és a gerincvelői szintű motoros működéseket irányító neuronhálózatok szerveződésének, kémiai tulajdonságainak, és fájdalom modellekben mutatott plaszticitásának vizsgálatát. Ennek megfelelően vizsgáltuk a nociceptív primer afferensek és a gerincvelői hátsó szarvi másodlagos érző neuronok közötti szinaptikus kapcsolatok molekuláris anatómiáját; a gerincvelő hátsó szarvi propriospinalis neuronok szinaptikus kapcsolatait, fiziológiai és neurokémiai tulajdonságait; a gerincvelő hátsó szarvi neuronhálózatok plaszticitását gyulladásos fájdalom modellben; és a gerincvelői motoros működések szabályozásában résztvevő premotor interneuronok neurokémiai tulajdoságait. Eredményeink jelentős mértékben hozzájárultak a gerincvelői neuronok morfológia, fiziológiai és neurokémiai tulajdonságainak pontosabb megértéséhez, és ezen keresztül ahhoz, hogy pontosabb képet alkothassunk a gerincvelői neuronoknak a nociceptív és motoros feladatok kivitelezésében betöltött szerepéről. Eredményeink hozzájárultak a fájdalomérzet kiváltásában szerepet játszó gerincvelői szintű szenzoros ingerület feldolgozási folyamatok pontosabb megértéséhez. Rávilágítottuk a figyelmet olyan molekulákra, amelyek eddig nem kaptak megfelelő figyelmet a fájdalomkutatásban. Eredeti megfigyeléseink kiindulópontul szolgálhatnak újabb, az eddigieknél hatékonyabb és kevésbe addiktív fájdalomcsillapító eljárások kidolgozásához. | The aim of the project was to investigate the organization and neurochemical properties of spinal neural circuits underlying nociceptive information processing and motor control. In addition, we also intended to study the plasticity of sensory neural microcircuits of the superficial spinal dorsal horn evoked by inflammatory chronic pain. Thus, we investigated the molecular anatomy of synaptic contacts between axon terminals of nociceptive primary afferents and secondary sensory spinal neurons; synaptic interconnectivity, physiological and neurochemical properties of propriospinal neuron in the superficial spinal dorsal horn; plasticity of spinal neural microcircuits evoked by chronic subcutaneous inflammation; and the chemical properties of premotor interneurons participating in the coordination of spinal motor activities. Our results provided a substantial contribution to the understanding of the morphological, physiological and neurochemical properties of spinal neurons, and also enabled us to obtain a better understanding about nociceptive and motor activities at the level of the spinal cord. We provided new insights into the organization of pain processing spinal microcircuits, fundamental mechanisms of activity-evoked neural plasticity. We have described molecular mechanisms that have not received enough attention in pain research till now. Our original observations may assist in developing effective therapeutic strategies for chronic pain syndromes.