Christophe Magnani

Control of neuronal persistent activity by voltage-dependent dendritic properties.

Neural integrators and working memory rely on persistent activity, a widespread neural phenomenon potentially involving persistent sodium conductances. Using a unique combination of voltage-clamp, dynamic-clamp, and frequency-domain techniques, we have investigated the role of voltage-dependent conductances on the dendritic electrotonic structure of neurons of the prepositus hypoglossi nucleus (PHN), which is known to be involved in oculomotor integration. The PHN contains two main neuronal populations: type B neurons with a double afterhyperpolarization and type D neurons, which not only are oscillatory but also have a greater electrotonic length than that of type B neurons. The persistent sodium conductance is present in all PHN neurons, although its effect on the dynamic electrotonic structure is shown to significantly differ in the two major cell types present in the nucleus. The electrotonic differences are such that the persistent sodium conductance can be almost perfectly manipulated in a type B neuron using an on-line dynamic clamp to add or subtract virtual sodium ion channels. The dynamic-clamp results are confirmed by data-fitted models, which suggest that the persistent sodium conductance has two different roles depending on its somatic versus dendritic location: perisomatic conductances could play a major role in maintaining action potential discharge and dendritic conductances would be more involved in other computational properties, such as those involving remote synaptic processing or bistable events.

Saccadic Velocity in the New Suppression Head Impulse Test: A New Indicator of Horizontal Vestibular Canal Paresis and of Vestibular Compensation

Objective To determine whether saccadic velocity in the suppression head impulse paradigm (SHIMP) test is a reliable indicator of vestibular loss at the acute and at the chronic stage in patients suffering from different vestibular pathologies. Methods Thirty-five normal subjects and 57 patients suffering from different vestibular pathologies associated with unilateral vestibular loss (UVL) or bilateral vestibular loss (BVL) were tested in the SHIMPs paradigm. SHIMPs were performed by turning the head 10 times at high velocities to the left or right side, respectively. The patients were instructed to fixate on a red spot generated by a head-fixed laser projected on the wall. In this SHIMPs paradigm, healthy subjects made a large anti-compensatory saccade at the end of the head turn (a SHIMP saccade). The peak saccadic velocity, the percentage of the trials completed with saccades in 10 trials, and the latency of the saccades were quantified in each group. A video-head impulse test (v-HIT) was systematically performed in all of our subjects as well as a caloric test. The dizziness handicap inventory questionnaire was also given to chronic UVL and BVL patients. Results At the acute stage after a complete UVL, patients had zero or a few anti-compensatory saccades for low velocity head turns toward the lesioned side. These saccades had lower velocity than the anti-compensatory saccades recorded during head rotation toward the intact side and/or compared with the saccades measured in control subjects. At the chronic stage, some of the patients recovered the ability to perform SHIMP saccades at each head turn toward the lesioned side, but very often these saccades were of significantly lower velocity. In BVL patients, no anti-compensatory saccades, or only significantly smaller ones, could be detected for head turns to both sides. Conclusion SHIMP is a specific and sensitive test to detect a complete horizontal canal loss at the acute stage. In addition, it reflects the ability of patients with moderate horizontal vestibulo–ocular reflex gain decrease to generate anti-compensatory saccades in the chronic stage. In association with v-HIT, it allows determination of the residual vestibular function and to detect anti-compensatory saccades.

Absence of Rotation Perception during Warm Water Caloric Irrigation in Some Seniors with Postural Instability.

Falls in seniors are a major public health problem. Falls lead to fear of falling, reduced mobility, and decreased quality of life. Vestibular dysfunction is one of the fall risk factors. The relationship between objective measures of vestibular responses and age has been studied. However, the effects of age on vestibular perception during caloric stimulation have not been studied. Twenty senior subjects were included in the study, and separated in two groups: 10 seniors reporting postural instability (PI) and exhibiting absence of vestibular perception when they tested with caloric stimulation and 10 sex- and age-matched seniors with no such problems (controls). We assessed vestibular perception on a binary rating scale during the warm irrigation of the caloric test. The function of the various vestibular receptors was assessed using video head impulse test (vHIT), caloric tests, and cervical and ocular vestibular-evoked myogenic potentials. The Equitest was used to evaluate balance. No horizontal canal dysfunction assessed using both caloric test and vHIT was detected in either group. No significant difference was detected between PI and control groups for the peak SPV of caloric-induced ocular nystagmus or for the HVOR gain. All the controls perceived rotation when the maximal SPV during warm irrigation was equal to or ≥15°/s. None of the subjects in the PI group perceived rotation even while the peak SPV exceeded 15°/s, providing objective evidence of normal peripheral horizontal canal function. All the PI group had abnormal Equitest results, particularly in the two last conditions. These investigations show for the first time that vestibular perception can be absent during a caloric test despite normal horizontal canal function. We call this as dissociation vestibular neglect. Patients with poor vestibular perception may not be aware of postural perturbations and so will not correct for them. Thus, falls in the elderly may result, among other factors, from a vestibular neglect due to an inappropriate central processing of normal vestibular peripheral inputs. That is, failure to perceive rotation during caloric testing when the SPV is >15°/s, should prompt the clinician to envisage preventive actions to avoid future falls such as rehabilitation.

A Novel Saccadic Strategy Revealed by Suppression Head Impulse Testing of Patients with Bilateral Vestibular Loss

Objective We examined the eye movement response patterns of a group of patients with bilateral vestibular loss (BVL) during suppression head impulse testing. Some showed a new saccadic strategy that may have potential for explaining how patients use saccades to recover from vestibular loss. Methods Eight patients with severe BVL [vestibulo-ocular reflex (VOR) gains less than 0.35 and absent otolithic function] were tested. All patients were given the Dizziness Handicap Inventory and questioned about oscillopsia during abrupt head movements. Two paradigms of video head impulse testing of the horizontal VOR were used: (1) the classical head impulse paradigm [called head impulse test (HIMPs)]—fixating an earth-fixed target during the head impulse and (2) the new complementary test paradigm—fixating a head-fixed target during the head impulse (called SHIMPs). The VOR gain of HIMPs was quantified by two algorithms. Results During SHIMPs testing, some BVL patients consistently generated an inappropriate covert compensatory saccade during the head impulse that required a corresponding large anti-compensatory saccade at the end of the head impulse in order to obey the instructions to maintain gaze on the head-fixed target. By contrast, other BVL patients did not generate this inappropriate covert saccade and did not exhibit a corresponding anti-compensatory saccade. The latencies of the covert saccade in SHIMPs and HIMPs were similar. Conclusion The pattern of covert saccades during SHIMPs appears to be related to the reduction of oscillopsia during abrupt head movements. BVL patients who did not report oscillopsia showed this unusual saccadic pattern, whereas BVL patients who reported oscillopsia did not show this pattern. This inappropriate covert SHIMPs saccade may be an objective indicator of how some patients with vestibular loss have learned to trigger covert saccades during head movements in everyday life.

Quadratic sinusoidal analysis of voltage clamped neurons

Nonlinear biophysical properties of individual neurons are known to play a major role in the nervous system, especially those active at subthreshold membrane potentials that integrate synaptic inputs during action potential initiation. Previous electrophysiological studies have made use of a piecewise linear characterization of voltage clamped neurons, which consists of a sequence of linear admittances computed at different voltage levels. In this paper, a fundamentally new theory is developed in two stages. First, analytical equations are derived for a multi-sinusoidal voltage clamp of a Hodgkin–Huxley type model to reveal the quadratic response at the ionic channel level. Second, the resulting behavior is generalized to a novel Hermitian neural operator, which uses an algebraic formulation capturing the entire quadratic behavior of a voltage clamped neuron. In addition, this operator can also be used for a nonlinear identification analysis directly applicable to experimental measurements. In this case, a Hermitian matrix of interactions is built with paired frequency probing measurements performed at specific harmonic and interactive output frequencies. More importantly, eigenanalysis of the neural operator provides a concise signature of the voltage dependent conductances determined by their particular distribution on the dendritic and somatic membrane regions of neurons. Finally, the theory is concretely illustrated by an analysis of an experimentally measured vestibular neuron, providing a remarkably compact description of the quadratic responses involved in the nonlinear processing underlying the control of eye position during head rotation, namely the neural integrator.

Nonlinear properties of medial entorhinal cortex neurons reveal frequency selectivity during multi-sinusoidal stimulation.

The neurons in layer II of the medial entorhinal cortex are part of the grid cell network involved in the representation of space. Many of these neurons are likely to be stellate cells with specific oscillatory and firing properties important for their function. A fundamental understanding of the nonlinear basis of these oscillatory properties is critical for the development of theories of grid cell firing. In order to evaluate the behavior of stellate neurons, measurements of their quadratic responses were used to estimate a second order Volterra kernel. This paper uses an operator theory, termed quadratic sinusoidal analysis (QSA), which quantitatively determines that the quadratic response accounts for a major part of the nonlinearity observed at membrane potential levels characteristic of normal synaptic events. Practically, neurons were probed with multi-sinusoidal stimulations to determine a Hermitian operator that captures the quadratic function in the frequency domain. We have shown that the frequency content of the stimulation plays an important role in the characteristics of the nonlinear response, which can distort the linear response as well. Stimulations with enhanced low frequency amplitudes evoked a different nonlinear response than broadband profiles. The nonlinear analysis was also applied to spike frequencies and it was shown that the nonlinear response of subthreshold membrane potential at resonance frequencies near the threshold is similar to the nonlinear response of spike trains.