Biomedical subjects

Cornelius Schwarz

Publications and source records attributed to Cornelius Schwarz.

11 recordsLinked to original sources

PubMed2006

Two psychophysical channels of whisker deflection in rats align with two neuronal classes of primary afferents.

The rat whisker system has evolved into in an excellent model system for sensory processing from the periphery to cortical stages. However, to elucidate how sensory processing finally relates to percepts, methods to assess psychophysical performance pertaining to precise stimulus kinematics are needed. Here, we present a head-fixed, behaving rat preparation that allowed us to measure detectability of a single whisker deflection as a function of amplitude and peak velocity. We found that velocity thresholds for detection of small-amplitude stimuli (<3 degrees) were considerably higher than for detection of large-amplitude stimuli (>3 degrees). This finding suggests the existence of two psychophysical channels mediating detection of whisker deflection: one channel exhibiting high amplitude and low velocity thresholds (W1), and the other channel exhibiting high velocity and low amplitude thresholds (W2). The correspondence of W1 to slowly adapting (SA) and W2 to rapidly adapting (RA) neuronal classes in the trigeminal ganglion was revealed in acute neurophysiological experiments. Neurometric plots of SA and RA cells were closely aligned to psychophysical performance in the corresponding W1 and W2 parameter ranges. Interestingly, neurometric data of SA cells fit the behavior best if it was based on a short time window integrating action potentials during the initial phasic response, in contrast to integrating across the tonic portion of the response. This suggests that detection performance in both channels is based on the assessment of very few spikes in their corresponding groups of primary afferents.

Afferent Pathways↗

PubMed2006

Effects of electrically coupled inhibitory networks on local neuronal responses to intracortical microstimulation.

Using in vivo multielectrode electrophysiology in mice, we investigated the underpinnings of a local, long-lasting firing rate suppression evoked by intracortical microstimulation. Synaptic inhibition contributes to this suppression as it was reduced by pharmacological blockade of gamma-aminobutyric acid type B (GABAB) receptors. Blockade of GABAB receptors also abolished the known sublinear addition of inhibitory response duration after repetitive electrical stimulation. Furthermore, evoked inhibition was weaker and longer in connexin 36 knockout (KO) mice that feature decoupled cortical inhibitory networks. In supragranular layers of KO mice even an unusually long excitatory response (< or = 50 ms) appeared that was never observed in wild-type (WT) mice. Furthermore, the spread and duration of very fast oscillations (> 200 Hz) evoked by microstimulation at a short latency were strongly enhanced in KO mice. In the spatial domain, lack of connexin 36 unmasked a strong anisotropy of inhibitory spread. Although its reach along layers was almost the same as that in WT mice, the spread across cortical depth was severely hampered. In summary, the present data suggest that connexin 36-coupled networks significantly shape the electrically evoked cortical inhibitory response. Electrical coupling renders evoked cortical inhibition more precise and strong and ensures a uniform spread along the two cardinal axes of neocortical geometry.

Animals↗

PubMed2006

Functional unity of the ponto-cerebellum: evidence that intrapontine communication is mediated by a reciprocal loop with the cerebellar nuclei.

The majority of cerebral signals destined for the cerebellum are handed over by the pontine nuclei (PN), which thoroughly reorganize the neocortical topography. The PN maps neocortical signals of wide-spread origins into adjacent compartments delineated by spatially precise distribution of cortical terminals and postsynaptic dendrites. We asked whether and how signals interact on the level of the PN. Intracellular fillings of rat PN cells in vitro did not reveal any intrinsic axonal branching neither within the range of the cells' dendrites nor farther away. Furthermore, double whole cell patch recordings did not show any signs of interaction between neighboring pontine cells. Using simultaneous unit recording in the PN and cerebellar nuclei (CN) in rats in vivo, we investigated whether PN compartments interact via extrinsic reciprocal connections with the CN. Repetitive electrical stimulation of the cerebral peduncle of < or = 40 Hz readily evoked rapid sequential activation of PN and CN, demonstrating a direct connection between the structures. Stimulation of the PN gray matter led to responses in neurons < or = 600 microm away from the stimulation site at latencies compatible with di- or polysynaptic pathways via the CN. Importantly, these interactions were spatially discontinuous around the stimulation electrode suggesting that reciprocal PN-CN loops in addition reflect the compartmentalized organization of the PN. These findings are in line with the idea that the cerebellum makes use of the compartmentalized map in the PN to orchestrate the composition of its own neocortical input.

Action Potentials↗

PubMed2005

Employing ICA and SOM for spike sorting of multielectrode recordings from CNS.

For classification of action potential shapes in multineuron recordings, we present a spike sorting system employing independent component analysis (ICA) and an unsupervised artificial neural network (Kohonen's self-organizing map, SOM). We focus on how ICA in the first stage of the spike sorting system can be used to address specific problems arising in recordings using multielectrode arrays in the CNS. Using real data recorded from the pontine nuclei in rats and simulated data, we evaluate the performance of several ICA algorithms to remove cross-talk between electrodes using data from continuous recording (or simulation). When using cut-out data, the standard format of extracellular spike recordings, new problems emerge and robust algorithms are needed. We demonstrate that several ICA algorithms show a good performance on cut-out data from multielectrode array recordings (simulated and real data). In tetrode recordings the same neuron is purposely recorded by several electrodes simultaneously and we show, how independent component analysis can be used in this case to identify redundant information and hence to compress relevant information, improving subsequent clustering of a SOM.

Action Potentials↗

PubMed2005

Central signals rapidly switch tactile processing in rat barrel cortex during whisker movements.

Palpatory movements ('active' touch) are an integral part of tactile sensing. It is known that tactile signals can be modulated in certain behavioral contexts, but it is still unresolved to what degree this modulation is related to movement kinematics and whether it stems from tactile receptors or from central sources. Using awake, head-fixed rats, trained to contact an object, we measured trajectories of muscle-propelled whisker movement precisely and compared tactile responses to contacts thus accomplished with 'passive' contacts (motionless whisker contacted by object). Multielectrode extracellular recordings in deep layers of barrel cortex revealed that when the animals moved their whiskers actively, tactile processing switched from high response amplitudes, wide cortical representation and low background firing, to low response amplitudes, narrow spatial representation and elevated background firing. Switching was fast (<100 ms) and unrelated to the degree of alertness as assessed by spectral analysis of pre-contact field potentials. Switching persisted when information about whisker kinematics was interrupted by transection of the infraorbital nerve and contacts were mimicked by peripheral electrical stimulation. Taken together, these characteristics render central signals derived from the motor system a likely contributor to the processing of active touch.

Adaptation, Physiological↗

PubMed2005

Organization of tectopontine terminals within the pontine nuclei of the rat and their spatial relationship to terminals from the visual and somatosensory cortex.

We investigated the spatial relationship of axonal and dendritic structures in the rat pontine nuclei (PN), which transfer visual signals from the superior colliculus (SC) and visual cortex (A17) to the cerebellum. Double anterograde tracing (DiI and DiAsp) from different sites in the SC showed that the tectal retinotopy of visual signals is largely lost in the PN. Whereas axon terminals from lateral sites in the SC were confined to a single terminal field close to the cerebral peduncle, medial sites in the SC projected to an additional dorsolateral one. On the other hand, axon terminals originating from the two structures occupy close but, nevertheless, totally nonoverlapping terminal fields within the PN. Furthermore, a quantitative analysis of the dendritic trees of intracellularly filled identified pontine projection neurons showed that the dendritic fields were confined to either the SC or the A17 terminal fields and never extended into both. We also investigated the projections carrying cortical somatosensory inputs to the PN as these signals are known to converge with tectal ones in the cerebellum. However, terminals originating in the whisker representation of the primary somatosensory cortex and in the SC were located in segregated pontine compartments as well. Our results, therefore, point to a possible pontocerebellar mapping rule: Functionally related signals, commonly destined for common cerebellar target zones but residing in different afferent locations, may be kept segregated on the level of the PN and converge only later at specific sites in the granular layer of cerebellar cortex.

Animals↗

PubMed2005

Spatial segregation of different modes of movement control in the whisker representation of rat primary motor cortex.

What is mapped on the surface of the primary motor cortex (M1)? The classic somatotopic map holds true on the level of limb representations. However, on the small scale (at within-limb representations), neither somatotopy nor movement dynamics/kinematics seem to be organizational principles. We investigated the hypothesis that integrated into the body representation of M1 there may be separate representation of different modes of motor control, using different subcortical computations but sharing the same motor periphery. Using awake rats and long intracortical stimulation trains in M1 whisker representation (wM1) revealed that natural-like, rhythmic whisking (normally used for tactile exploration) can be evoked from a posteromedial subregion of wM1. Nonrhythmic whisker retraction, on the other hand, was evoked in an adjacent but more anterolaterally located region within wM1. Evoked whisker retraction was always accompanied by complex movements of the face, suggesting that the respective subregion is able to interact with other representations in specific behavioral contexts. Such associations were absent for evoked rhythmic whisking. The respective subregion rather seemed to activate a downstream central pattern generator, the oscillation frequency of which was dependent on the average evoked cortical activity. Nevertheless, joint stimulation of the two neighboring subregions demonstrated their potency to interact in a functionally useful way. Therefore, we suggest that the cause of cortical separation is the specific drive of subcortical structures needed to generate different types of movements rather than different behavioral contexts in which the movements are performed.

Animals↗

PubMed2005

Neocortex is the major target of sedative concentrations of volatile anaesthetics: strong depression of firing rates and increase of GABAA receptor-mediated inhibition.

General anaesthetics cause sedation, amnesia and hypnosis. Although these clinically desired actions are indicative of an impairment of neocortical information processing, it is widely held that they are to a large part mediated by subcortical neural networks. Anaesthetic action on brain stem, basal forebrain and thalamus, all of which are known to modulate cortical excitability, would thus ultimately converge on neocortex, perturbing and reducing action potential activity therein. However, as neocortex harbours molecular targets of anaesthetics in high densities, notably GABA(A) receptors, neocortex itself should be very sensitive to anaesthetics. Here, we performed experiments to reveal the extent to which neocortex proper is a relevant target of the low concentrations of volatile anaesthetics causing sedation and hypnosis. We compared the effects of isoflurane, enflurane and halothane on spontaneous action potential activity of rat neocortical neurons in vivo and in isolated cortical networks in vitro, i.e. in the presence and absence of subcortical arousal systems. We observed that the anaesthetics decreased spontaneous firing of neurons via intracortical mechanisms; concentrations inducing hypnosis in humans reduced discharge rates both in vivo and in vitro to the same extent, approximately 50%. This decrease in neuronal activity was paralleled by a significant enhancement of neocortical GABA(A) receptor-mediated inhibition. These findings challenge the notion of predominantly subcortical effects of volatile anaesthetics and suggest that intracortical targets, among them neocortical GABA(A) receptors, mediate the sedative and hypnotic properties of volatile anaesthetics.

Action Potentials↗

PubMed2003

Spatiotemporal effects of microstimulation in rat neocortex: a parametric study using multielectrode recordings.

Using microstimulation to imprint meaningful activity patterns into intrinsically highly interconnected neuronal substrates is hampered by activation of fibers of passage leading to a spatiotemporal "blur" of activity. The focus of the present study was to characterize the shape of this blur in the neocortex to arrive at an estimate of the resolution with which signals can be transmitted by multielectrode stimulation. The horizontal spread of significant unit activity evoked by near-threshold focal electrical stimulation (charge transfer 0.8-4.8 nC) and multielectrode recording in the face representation of the primary somatosensory cortex of ketamine anesthetized rats was determined to be about 1,350 microm. The evoked activity inside this range consisted in a sequence of fast excitatory response followed by an inhibition lasting >100 ms. These 2 responses could not be separated by varying the intensity of stimulation while a slow excitatory rebound after the inhibitory response was restricted to higher stimulus intensities (>2.4 nC). Stimulation frequencies of 20 and 40 Hz evoked repetitive excitatory response standing out against a continuous background of inhibition. At 5- and 10-Hz stimulation, the inhibitory response showed a complex interaction pattern attributed to highly sublinear superposition of individual inhibitory responses. The present data help to elucidate the neuronal underpinnings of behavioral effects of microstimulation. Furthermore, they provide essential information to determine spatiotemporal constraints for purposeful multielectrode stimulation in the neocortex.

Action Potentials↗

PubMed2003

Efficacy and short-term plasticity at GABAergic synapses between Purkinje and cerebellar nuclei neurons.

Although the entire output of the cerebellar cortex is conveyed to the deep cerebellar nuclei neurons (DCNs) via the GABAergic synapses established by Purkinje cells (PCs), very little is known about the strength and dynamic properties of PC-DCN connections. Here we show that activation of PC-DCN unitary connections induced large conductance changes (11.7 nS) in DCNs recorded in whole cell patch configuration in acute slices, suggesting that activity of single PCs might significantly affect the output of its target neurons. Based on the large unitary quantal content (18) inferred from calculations of PC-DCN quantal size (0.65 nS) and the near absence of failures in synaptic transmission during control conditions, we conclude that PC-DCN connections are highly multi-sited. The analysis of dynamic properties of PC-DCN synapses demonstrated remarkable paired pulse depression (PPD), maximal at short intervals (paired pulse ratio of 0.15 at 7-ms interval). We provide evidence that PPD is presynaptic in origin and release-independent. In addition, multiple pulse stimulation revealed that PC-DCN synapses exhibited larger sensitivity to dynamic than to steady signals. We postulate that the, otherwise paradoxical, combination of marked short-term depression with strong multi-sited connections is optimal to transfer dynamic information at unitary level by performing spatial average of release probability across the numerous release sites. This feature could enable these synapses to encode presynaptic time-varying signals of single PCs as moment-to-moment changes in synaptic strength, a capacity well suited to the postulated role of cerebellum in control of temporal aspects of motor or cognitive behaviors.

Animals↗

PubMed2002

Serotonergic control of cerebellar mossy fiber activity by modulation of signal transfer by rat pontine nuclei neurons.

Serotonergic modulation of precerebellar nuclei may be crucial for the function of the entire cerebellar system. To study the effects of serotonin (5-HT) on neurons located within the pontine nuclei (PN), the main source of cerebellar mossy fibers, we performed standard intracellular recordings from PN neurons in a slice preparation of the rat pontine brain stem. Application of 5 microM 5-HT significantly altered several intrinsic membrane properties of PN neurons. First, it depolarized the somatic membrane potential by 6.5 +/- 3.5 mV and increased the apparent input resistance from 49.5 +/- 14.6 to 62.7 +/- 21.1 MOmega. Second, 5-HT altered the I-V relationship of PN neurons: it decreased the inward rectification in hyperpolarizing direction, but increased it when depolarizing currents were applied. Third, it decreased the rheobase from 0.32 +/- 0.14 to 0.24 +/- 0.14 nA without affecting the firing threshold. Finally, the amplitude of medium-duration after hyperpolarizations was reduced from -14.9 +/- 2.0 to -12.3 +/- 2.4 mV. Together, these 5-HT effects on the intrinsic membrane properties result in an increase in excitability and instantaneous firing rate. In addition, application of 5 microM 5-HT also modulated postsynaptic potentials (PSPs) evoked by electric stimulations within the cerebral peduncle. The amplitude, maximal slope, and integral of these PSPs were reduced to 46.2 +/- 23.4%, 45.7 +/- 23.7%, and 61.4 +/- 28.4% of the control value, respectively. In contrast, we found no change in the decay and voltage dependence of PSPs. To test modulatory effects on short-term synaptic facilitation, we applied pairs of electrical stimuli at intervals between 10 and 1,000 ms. 5-HT selectively enhanced the paired-pulse facilitation for interstimulus-intervals >20 ms. The alteration of paired-pulse facilitation points to a presynaptic site of action for 5-HT effects on synaptic transmission. Pharmacological experiments suggested that pre- and postsynaptic effects of 5-HT were mediated by two different kinds of 5-HT receptors: changes in intrinsic membrane properties were blocked by the 5-HT(2) receptor antagonist cinanserin while the reduction of PSPs was prevented by the 5-HT(1) receptor antagonist cyanopindolol. In conclusion, 5-HT increases the excitability of PN neurons but decreases the synaptic transmission on them. The selective enhancement of synaptic facilitation may, however, allow high-frequency inputs to effectively drive PN neurons, thus the PN may act as a high-pass filter during periods of 5-HT release.

Animals↗