Gideon Gradwohl

Dendritic voltage dependent conductances increase the excitatory synaptic response and its postsynaptic inhibition in a reconstructed α-motoneuron: A computer model

Abstract Mammalian spinal monosynaptic Ia EPSP and its postsynaptic reciprocal depolarizing inhibition was studied using NEURON simulator in a morphologically and physiologically characterised α -motoneuron. Low g Na and g K located at the dendrites greatly enhanced EPSP A+N maximal amplitude and its reciprocal inhibition. A small area of active dendrite is sufficient for obtaining the maximal increase in excitatory response for each g Na . EPSP peak is monotonically augmented by raising g Na , whereas inhibition is enhanced until a specific g Na and a further increase diminishes the inhibitory effect. Computer simulations performed at four additional α -motoneurons yielded similar results.

Chronic Upper Airway Obstruction Induces Abnormal Sleep/Wake Dynamics in Juvenile Rats

Objectives Conventional scoring of sleep provides little information about the process of transitioning between vigilance-states. We used the state space technique to explore whether rats with chronic upper airway obstruction (UAO) have abnormal sleep/wake states, faster movements between states, or abnormal transitions between states. Design The tracheae of 22-day-old Sprague-Dawley rats were surgically narrowed to increase upper airway resistance with no evidence for frank obstructed apneas or hypopneas; 24-h electroencephalography of sleep/wake recordings of UAO and sham-control animals was analyzed using state space technique. This non-categorical approach allows quantitative and unbiased examination of vigilance-states and state transitions. Measurements were performed 2 weeks post-surgery at baseline and following administration of ritanserin (5-HT2 receptor antagonist) the next day to stimulate sleep. Measurements and Results UAO rats spent less time in deep (delta-rich) slow wave sleep (SWS) and near transition zones between states. State transitions from light SWS to wake and vice versa and microarousals were more frequent and rapid in UAO rats, indicating that obstructed animals have more regions where vigilance-states are unstable. Ritanserin consolidated sleep in both groups by decreasing the number of microarousals and trajectories between wake and light SWS, and increasing deep SWS in UAO. Conclusions State space technique enables visualization of vigilance-state transitions and velocities that were not evident by traditional scoring methods. This analysis provides new quantitative assessment of abnormal vigilance-state dynamics in UAO in the absence of frank obstructed apneas or hypopneas.

Homogeneous distribution of excitatory and inhibitory synapses on the dendrites of the cat surea triceps α-motoneurons increases synaptic efficacy: Computer model

Abstract The effects of input distribution in dendrites on postsynaptic inhibition of spinal monosynaptic reflex were studied in morphologically and physiologically characterized α-motoneurons. In homogeneous (HOM) and heterogeneous (HEM) models, the location of the excitatory and inhibitory synapses was randomly selected for each bin of dendritic length. In the HOM, each compartment was forced to contain only one synapse as long as other compartments did not have at least one synapse. In the HEM, no restriction was made for synaptic distribution within a bin. EPSP amplitude in the HOM was enhanced by 28% and inhibition of EPSP peak (upon activation of inhibition) was increased by 66%, compared to the HEM. These results indicate that synaptic efficacy is greater in the HOM, both for excitatory and inhibitory synapses. Thus, it is suggested that homogeneously distributed postsynaptic inhibition may serve as the powerful inhibition of the monosynaptic reflex in realistic α-motoneurons.

Sleep/Wake Dynamics Changes during Maturation in Rats

Objectives Conventional scoring of sleep provides little information about the process of transitioning between vigilance states. We applied the state space technique (SST) using frequency band ratios to follow normal maturation of different sleep/wake states, velocities of movements, and transitions between states of juvenile (postnatal day 34, P34) and young adult rats (P71). Design 24-h sleep recordings of eight P34 and nine P71 were analyzed using conventional scoring criteria and SST one week following implantation of telemetric transmitter. SST is a non-categorical approach that allows novel quantitative and unbiased examination of vigilance-states dynamics and state transitions. In this approach, behavioral changes are described in a 2-dimensional state space that is derived from spectral characteristics of the electroencephalography. Measurements and Results With maturation sleep intensity declines, the duration of deep slow wave sleep (DSWS) and light slow wave sleep (LSWS) decreases and increases, respectively. Vigilance state determination, as a function of frequency, is not constant; there is a substantial shift to higher ratio 1 in all vigilance states except DSWS. Deep slow wave sleep decreases in adult relative to juvenile animals at all frequencies. P71 animals have 400% more trajectories from Wake to LSWS (p = 0.005) and vice versa (p = 0.005), and 100% more micro-arousals (p = 0.021), while trajectories from LSWS to DSWS (p = 0.047) and vice versa (p = 0.033) were reduced by 60%. In both juvenile and adult animals, no significant changes were found in sleep velocity at all regions of the 2-dimensional state space plot; suggesting that maturation has a partial effect on sleep stability. Conclusions Here, we present novel and original evidence that SST enables visualization of vigilance-state intensity, transitions, and velocities that were not evident by traditional scoring methods. These observations provide new perspectives in sleep state dynamics and highlight the usefulness of this technique in exploring the development of sleep-wake activity.

Analysis of dendritic distribution of voltage-dependent channels effects on EPSP and its reciprocal inhibition in α-motoneurons: computer model

Abstract Modeling of excitation and inhibition of morphologically and physiologically characterized triceps surea motoneuron (MN 42) was executed by a NEURON simulator. The voltage-dependent channels of MN 42 were allocated on six dendrites (the rest six dendrites remained passive) according to three types of distribution functions: a step function (SF), an exponential decay (ED, highest density proximally to the soma) and exponential rise (ER, highest density distally to the soma). Maximal densities of the sodium conductance varied between 0.01 and 0.06 S/cm 2 . The peak of the EPSP became larger as the maximal density of the voltage-dependent channels is increased. In the SF distribution, with the highest total conductance (G, Siemens), the EPSP amplitudes were greater than these in the ER and ED models. The reciprocal EPSP inhibition in the model with the SF was most efficient in comparison to the ED and ER models. EPSP peak inhibition at ED and ER are similar, despite that the total active conductance in ED is about 10 times smaller than in ER distribution. The dependency of the inhibition on the density of the active conductance in the SF and ED models is not linear. We conclude that in an “ideal neuron” the presence of proximal voltage-dependent channels may boost distally located synaptic inputs thus “normalizing” the synaptic responses.

Chronic upper airway obstruction induces abnormal sleep/wake dynamics in juvenile rats

Traditional scoring of sleep provides little information about the process of transitioning between vigilance-states. We hypothesized that chronic upper airway obstruction (UAO) will lead to sleep instability in the absence of frank obstructed apneas or hypopneas. Using an approach similar to previous reports [1,2] defined a 2-dimensional (2D) state space technique (SST) using 2 spectral amplitude ratios calculated by dividing integrated spectral amplitudes at selected frequency bands. We calculated two spectral amplitude ratios by integrating the spectral amplitude over specific frequencies: 0.5-20/0.5-40 Hz for ratio 1 and 0.5-4/0.5-9 Hz for ratio 2. Each second of this ratio was mapped into the 2D state space, ratio 2 vs. ratio 1 (Figure ​(Figure1).1). State space analysis yields wake at low ratio 1 values and SWS at high ratio 1 values. We used the SST to explore whether the abnormal sleep in UAO reflects sleep instability, faster movements, and abnormal transitions between vigilance-states. Figure 1 Spontaneous sleep in rats. Values of wake (W), light slow wave sleep (LSWS), deep slow wave sleep (DSWS) and paradoxical sleep (PS) are shown. We analyzed whole day electroencephalography sleep/wake recordings of UAO and sham control juvenile Sprague-Dawley rats using SST. SST is a non-categorical approach allowing quantitative and unbiased examination of sleep/wake states and state transitions. Measurements of sleep/wake recordings were performed at baseline and following administration of ritanserin (5-HT2 receptor antagonist) the next day to stimulate sleep. UAO rats spent less time in deep (delta-rich) slow wave sleep (SWS) and near transition zones between states. Sleep state transitions were more frequent and rapid in UAO rats, indicating that obstructed animals have more regions where vigilance-states are unstable. The number of microarousals and trajectories from light SWS to wake and vice versa increased in the UAO group. Ritanserin consolidated sleep in both groups by decreasing the number of microarousals and trajectories between wake to light SWS, and increasing deep SWS in UAO.

Statistical computer model analysis of the reciprocal and recurrent inhibitions of the ia-epsp in α-motoneurons

We simulate the inhibition of Ia-glutamatergic excitatory postsynaptic potential (EPSP) by preceding it with glycinergic recurrent (REN) and reciprocal (REC) inhibitory postsynaptic potentials (IPSPs). The inhibition is evaluated in the presence of voltage-dependent conductances of sodium, delayed rectifier potassium, and slow potassium in five -motoneurons (MNs). We distribute the channels along the neuronal dendrites using, alternatively, a density function of exponential rise (ER), exponential decay (ED), or a step function (ST). We examine the change in EPSP amplitude, the rate of rise (RR), and the time integral (TI) due to inhibition. The results yield six major conclusions. First, the EPSP peak and the kinetics depending on the time interval are either amplified or depressed by the REC and REN shunting inhibitions. Second, the mean EPSP peak, its TI, and RR inhibition of ST, ER, and ED distributions turn out to be similar for analogous ranges of G. Third, for identical G, the large variations in the parameters’ values can be attributed to the sodium conductance step () and the active dendritic area. We find that small on a few dendrites maintains the EPSP peak, its TI, and RR inhibition similar to the passive state, but high on many dendrites decrease the inhibition and sometimes generates even an excitatory effect. Fourth, the MNs input resistance does not alter the efficacy of EPSP inhibition. Fifth, the REC and REN inhibitions slightly change the EPSP peak and its RR. However, EPSP TI is depressed by the REN inhibition more than the REC inhibition. Finally, only an inhibitory effect shows up during the EPSP TI inhibition, while there are both inhibitory and excitatory impacts on the EPSP peak and its RR.

A computer model of EPSP time integral modulation by the spatial distribution of dendritic voltage-dependent channels at a realistic α-motoneuron

Neuronal dendrites contain thousands of synaptic inputs and are the first phase for signal processing. The activation of dendritic voltage dependent currents modulates the amplitude and time course of synaptic inputs, thus when the synaptic potential finally reaches the soma, it is a highly transformed version of the original input. In a previous publication [1] we simulated the effect of inhibition on the EPSP peak under various conditions of voltage dependent channel activation. In the present study we analyze the effects of similar conditions on EPSP time integral and its inhibition, since this parameter is also important in determining the firing pattern of a neuron.