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Biomedical subjects

Michael Rudolph

Publications and source records attributed to Michael Rudolph.

15 recordsLinked to original sources

Biophysical and phenomenological models of multiple spike interactions in spike-timing dependent plasticity.

Spike-timing dependent plasticity (STDP) is a form of associative synaptic modification which depends on the respective timing of pre- and post-synaptic spikes. The biophysical mechanisms underlying this form of plasticity are currently not known. We present here a biophysical model which captures the characteristics of STDP, such as its frequency dependency, and the effects of spike pair or spike triplet interactions. We also make links with other well-known plasticity rules. A simplified phenomenological model is also derived, which should be useful for fast numerical simulation and analytical investigation of the impact of STDP at the network level.

Action Potentials↗

Inferring network activity from synaptic noise.

During intense network activity in vivo, cortical neurons are in a high-conductance state, in which the membrane potential (V(m)) is subject to a tremendous fluctuating activity. Clearly, this "synaptic noise" contains information about the activity of the network, but there are presently no methods available to extract this information. We focus here on this problem from a computational neuroscience perspective, with the aim of drawing methods to analyze experimental data. We start from models of cortical neurons, in which high-conductance states stem from the random release of thousands of excitatory and inhibitory synapses. This highly complex system can be simplified by using global synaptic conductances described by effective stochastic processes. The advantage of this approach is that one can derive analytically a number of properties from the statistics of resulting V(m) fluctuations. For example, the global excitatory and inhibitory conductances can be extracted from synaptic noise, and can be related to the mean activity of presynaptic neurons. We show here that extracting the variances of excitatory and inhibitory synaptic conductances can provide estimates of the mean temporal correlation-or level of synchrony-among thousands of neurons in the network. Thus, "probing the network" through intracellular V(m) activity is possible and constitutes a promising approach, but it will require a continuous effort combining theory, computational models and intracellular physiology.

Animals↗

Characterization of synaptic conductances and integrative properties during electrically induced EEG-activated states in neocortical neurons in vivo.

The activation of the electroencephalogram (EEG) is paralleled with an increase in the firing rate of cortical neurons, but little is known concerning the conductance state of their membrane and its impact on their integrative properties. Here, we combined in vivo intracellular recordings with computational models to investigate EEG-activated states induced by stimulation of the brain stem ascending arousal system. Electrical stimulation of the pedonculopontine tegmental (PPT) nucleus produced long-lasting (approximately 20 s) periods of desynchronized EEG activity similar to the EEG of awake animals. Intracellularly, PPT stimulation locked the membrane into a depolarized state, similar to the up-states seen during deep anesthesia. During these EEG-activated states, however, the input resistance was higher than that during up-states. Conductance measurements were performed using different methods, which all indicate that EEG-activated states were associated with a synaptic activity dominated by inhibitory conductances. These results were confirmed by computational models of reconstructed pyramidal neurons constrained by the corresponding intracellular recordings. These models indicate that, during EEG-activated states, neocortical neurons are in a high-conductance state consistent with a stochastic integrative mode. The amplitude and timing of somatic excitatory postsynaptic potentials were nearly independent of the position of the synapses in dendrites, suggesting that EEG-activated states are compatible with coding paradigms involving the precise timing of synaptic events.

Animals↗

Quality of life in mothers of speech impaired children.

Today, health-related quality of life (HRQOL) is an important outcome parameter in medicine. As a mother's well-being is important for the development of her child it is assumed that her HRQOL influences her child. In children with developmental disorders mothers may experience a reduction of their HRQOL. This study focused on HRQOL in mothers of speech impaired children. In 91 mothers the SF-36 questionnaire revealed lower scores of all subscales except for 'bodily pain' and 'mental health'. Although the data allow for no conclusion on whether the speech impairment is the reason or the consequence of a reduced HRQOL, the results indicate the necessity to take into account the mothers' well-being when dealing with speech impaired children.

Adult↗

A method to estimate synaptic conductances from membrane potential fluctuations.

In neocortical neurons, network activity can activate a large number of synaptic inputs, resulting in highly irregular subthreshold membrane potential (V(m)) fluctuations, commonly called "synaptic noise." This activity contains information about the underlying network dynamics, but it is not easy to extract network properties from such complex and irregular activity. Here, we propose a method to estimate properties of network activity from intracellular recordings and test this method using theoretical and experimental approaches. The method is based on the analytic expression of the subthreshold V(m) distribution at steady state in conductance-based models. Fitting this analytic expression to V(m) distributions obtained from intracellular recordings provides estimates of the mean and variance of excitatory and inhibitory conductances. We test the accuracy of these estimates against computational models of increasing complexity. We also test the method using dynamic-clamp recordings of neocortical neurons in vitro. By using an on-line analysis procedure, we show that the measured conductances from spontaneous network activity can be used to re-create artificial states equivalent to real network activity. This approach should be applicable to intracellular recordings during different network states in vivo, providing a characterization of the global properties of synaptic conductances and possible insight into the underlying network mechanisms.

Electricity↗

A fast-conducting, stochastic integrative mode for neocortical neurons in vivo.

During activated states, neocortical neurons receive intense synaptic background activity that induces large-amplitude membrane potential fluctuations and a strong conductance in the membrane. However, little is known about the integrative properties of neurons during such high-conductance states. Here we investigated the integrative properties of neocortical pyramidal neurons under in vivo conditions simulated by computational models. We show that the presence of high-conductance fluctuations induces a stochastic state in which active dendrites are fast conducting and have a different dynamics of initiation and forward-propagation of Na+-dependent spikes. Synaptic efficacy, quantified as the probability that a synaptic input specifically evokes a somatic spike, was approximately independent of the dendritic location of the synapse. Synaptic inputs evoked precisely timed responses (milliseconds), which also showed a reduced location dependence. This scheme was found to apply to a broad range of kinetics and density distributions of voltage-dependent conductances, as well as to different dendritic morphologies. Synaptic efficacies were, however, modulable by the balance of excitation and inhibition in background activity, for all synapses at once. Thus, models predict that the intense synaptic activity in vivo can confer advantageous computational properties to neocortical neurons: they can be set to an integrative mode that is stochastic, fast conducting, and optimized to process synaptic inputs at high temporal resolution independently of their position in the dendrites. Some of these predictions can be tested experimentally.

Action Potentials↗

Anxiety and depression in mothers of speech impaired children.

OBJECTIVE: In the adult population, anxiety and depression are the most frequent emotional disorders. In cases when mothers of speech impaired children are affected by these disorders may significantly influence the development of the child. The purpose of this study was to assess the prevalence of anxiety and depression in mothers of speech impaired children as literature provides only little information on this topic. METHODS: Hundred mothers (age 33.4 +/- 5.3 years, range: 22-47 years) of 100 preschool children (32 girls, 68 boys; age 4.2 +/- 1.5 years, range 1;3-7;7 years) with a speech impairment were investigated. Children with cochlear hearing loss, syndromes or other developmental disorders were excluded from the study. To estimate the prevalence of anxiety disorders and depression in the mothers the German version of the Hospital Anxiety and Depression Scale (HADS) was used. Data from 157 healthy women from the German test manual served as controls. Microsoft Excel and Matlab software packages were used for description, analysis, and evaluation. The differences in prevalence rates were tested by chi2-test and Wilcoxon's rank sum test. RESULTS: Assessed by the HADS-depression subscale 11% of the mothers of speech impaired children met criteria for depression compared to 2.5% in the control group. The prevalence in the study group was significantly higher (P < 1%). The prevalence of anxiety disorders did not differ from normative data on a significant level (P > 5%). CONCLUSIONS: Screening mothers of speech impaired children for depression is of significant clinical interest. For this purpose, the HADS is a suitable test. Further studies are necessary to investigate the influence of speech impairment and its development on the severity and development of mothers' depression. Up to now, no data exist about how fathers of speech impaired children react emotionally, so this question has to be focused on in future.

Adult↗

European brown hare syndrome virus in free-ranging European brown hares from Argentina.

From 1998 to 2000, serum samples of 80 shot European brown hares (Lepus europaeus) from Argentina were examined for antibodies against European brown hare syndrome virus (EBHSV) and 80 spleen samples were tested for EBHSV-antigen by enzyme linked immunosorbent assay (ELISA). Nine hares were positive for EBHSV-antigen. Antibodies against EBHSV were detected in only one individual. Based on negative staining electron microscopy of spleen homogenates, we observed calicivirus in one of five EBHSV-antigen positive hares. However, EBHS has not been reported to cause abnormal mortality in these hares. This is the first report of antibodies to EBHSV, EBHSV-antigen, and electron microscopy findings in free-ranging European brown hares from South America.

Animals↗

Biology of ovine adenovirus infection of nonpermissive cells.

Nonhuman adenoviruses, including those of the genus Atadenovirus, have the potential to serve as vectors for vaccine and gene therapy applications in humans, since they are resistant to preexisting immunity induced by human adenoviruses in the majority of the population. In this study, we elucidate the outcome of infection by ovine adenovirus type 7 isolate 287 (OAdV) of several nonovine cell types. We show here that OAdV infects a wide range of nonovine cells but is unable to complete its replication cycle in any of them. In nonovine, nonfibroblast cells, viral replication is blocked at an early stage before the onset of, or early in, DNA replication. Some fibroblasts, on the other hand, allow viral DNA replication but block virus production at a later stage during or after the translation of late viral proteins. Late viral proteins are expressed in cells where viral DNA replication takes place, albeit at a reduced level. Significantly, late proteins are not properly processed, and their cellular distribution differs from that observed in infected ovine cells. Thus, our results clearly show that OAdV infection of all nonovine cells tested is abortive even if significant viral DNA replication occurs. These findings have significant positive implications with respect to the safety of the vector system and its future use in humans.

Adenoviridae↗

Virologic investigations of free-living European bison (Bison bonasus) from the Bialowieza Primeval Forest, Poland.

We conducted virologic investigations on postmortem specimens from 261 free-living European bison (Bison bonasus) from the Bialowieza Primeval Forest, Poland collected between 1990 and 2000. Fifty-four of 94 males had balanoposthitis; none of the 167 female bison examined had reproductive tract lesions. Peripheral blood, swabs, and various tissues were analyzed for bovine viruses as well as for viral DNA by bovine herpesvirus 1 (BoHV-1) and bovine herpesvirus 4 (BoHV-4) specific polymerase chain reaction (PCR) technique. An infectious bovine rhinotracheitis like BoHV-1 strain was isolated from the spleen of a female bison calf and additionally was detected by nested PCR from splenic tissue. None of the bison had significant antibody titers against BoHV-1, bovine herpesvirus 2, BoHV-4, caprine herpesvirus 1, cervid herpesvirus 1, or bovine viral diarrhea (BVD) virus-1. However, low antibody titers in two animals indicate that this European bison population has been exposed to BVD virus or BVD-like viruses and BoHV-2.

Animals↗

Tuning neocortical pyramidal neurons between integrators and coincidence detectors.

Do cortical neurons operate as integrators or as coincidence detectors? Despite the importance of this question, no definite answer has been given yet, because each of these two views can find its own experimental support. Here we investigated this question using models of morphologically-reconstructed neocortical pyramidal neurons under in vivo like conditions. In agreement with experiments we find that the cell is capable of operating in a continuum between coincidence detection and temporal integration, depending on the characteristics of the synaptic inputs. Moreover, the presence of synaptic background activity at a level comparable to intracellular measurements in vivo can modulate the operating mode of the cell, and act as a switch between temporal integration and coincidence detection. These results suggest that background activity can be viewed as an important determinant of the integrative mode of pyramidal neurons. Thus, background activity not only sharpens cortical responses but it can also be used to tune an entire network between integration and coincidence detection modes.

Action Potentials↗

Spike generating dynamics and the conditions for spike-time precision in cortical neurons.

Temporal precision of spiking response in cortical neurons has been a subject of intense debate. Using a canonical model of spike generation, we explore the conditions for precise and reliable spike timing in the presence of Gaussian white noise. In agreement with previous results we find that constant stimuli lead to imprecise timing, while aperiodic stimuli yield precise spike timing. Under constant stimulus the neuron is a noise perturbed oscillator, the spike times follow renewal statistics and are imprecise. Under an aperiodic stimulus sequence, the neuron acts as a threshold element; the firing times are precisely determined by the dynamics of the stimulus. We further study the dependence of spike-time precision on the input stimulus frequency and find a non-linear tuning whose width can be related to the locking modes of the neuron. We conclude that viewing the neuron as a non-linear oscillator is the key for understanding spike-time precision.

Animals↗

Extracting information from the power spectrum of synaptic noise.

In cortical neurons, synaptic "noise" is caused by the nearly random release of thousands of synapses. Few methods are presently available to analyze synaptic noise and deduce properties of the underlying synaptic inputs. We focus here on the power spectral density (PSD) of several models of synaptic noise. We examine different classes of analytically solvable kinetic models for synaptic currents, such as the "delta kinetic models," which use Dirac delta functions to represent the activation of the ion channel. We first show that, for this class of kinetic models, one can obtain an analytic expression for the PSD of the total synaptic conductance and derive equivalent stochastic models with only a few variables. This yields a method for constraining models of synaptic currents by analyzing voltage-clamp recordings of synaptic noise. Second, we show that a similar approach can be followed for the PSD of the the membrane potential (Vm) through an effective-leak approximation. Third, we show that this approach is also valid for inputs distributed in dendrites. In this case, the frequency scaling of the Vm PSD is preserved, suggesting that this approach may be applied to intracellular recordings of real neurons. In conclusion, using simple mathematical tools, we show that Vm recordings can be used to constrain kinetic models of synaptic currents, as well as to estimate equivalent stochastic models. This approach, therefore, provides a direct link between intracellular recordings in vivo and the design of models consistent with the dynamics and spectral structure of synaptic noise.

Animals↗

Anxiety, depression, and quality of life in mothers of children with cleft lip/palate.

Multidisciplinary care for patients with cleft lip and palate (CLP) includes the surgical correction of the facial disfigurement and the rehabilitation of functional deficits to optimize the communicational competence of the affected patient. Although the well-being of the mother of a CLP child is an important protective factor for the child, up to now literature has paid only little attention to this topic. In this study, 50 mothers of CLP children aged 1-10 years were examined using the 36-item Short-Form Health Survey and the Hospital Anxiety and Depression Scale (HADS) to screen for quality of life, anxiety and depression. Surprisingly, the data obtained indicate no group-specific alterations of these items when compared with normal controls. In cases with a deteriorated quality of life, the results of the HADS were pathologic as well. In general, mothers of CLP children aged more than 12 months do not require psychological screening. In individual cases, screening for relevant emotional aspects may be restricted to using the HADS.

Adult↗