Oscillatory and Intrinsic Membrane Properties of Guinea Pig Nucleus Prepositus Hypoglossi Neurons In Vitro

Abstract

. Numerous models of the oculomotor neuronal integrator located in the prepositus hypoglossi nucleus (PHN) involve both highly tuned recurrent networks and intrinsic neuronal properties; however, there is little experimental evidence for the relative role of these two mechanisms. The experiments reported here show that all PHN neurons (PHNn) show marked phasic behavior, which is highly oscillatory in ϳ25% of the population. The behavior of this subset of PHNn, referred to as type D PHNn, is clearly different from that of the medial vestibular nucleus neurons, which transmit the bulk of head velocity-related sensory vestibular inputs without integrating them. We have investigated the firing and biophysical properties of PHNn and developed data-based realistic neuronal models to quantitatively illustrate that their active conductances can produce the oscillatory behavior. Although some individual type D PHNn are able to show some features of mathematical integration, the lack of robustness of this behavior strongly suggests that additional network interactions, likely involving all types of PHNn, are essential for the neuronal integrator. Furthermore, the relationship between the impulse activity and membrane potential of type D PHNn is highly nonlinear and frequency-dependent, even for relatively smallamplitude responses. These results suggest that some of the synaptic input to type D PHNn is likely to evoke oscillatory responses that will be nonlinearly amplified as the spike discharge rate increases. It would appear that the PHNn have specific intrinsic properties that, in conjunction with network interconnections, enhance the persistent neural activity needed for their function.

Control of Neuronal Persistent Activity by Voltage-Dependent Dendritic Properties

“…1 and Table 1) are similar to those obtained in a previous classification (Idoux et al 2006): type A-like neurons do not have a biphasic AHP (dAHP ϭ 0), their spikes are broader, and their AHPR is more pronounced than that for type B-like neurons. Furthermore, if the presence of oscillations, a qualitative parameter, is used, type A-like neurons can be further subdivided, as in the guinea pig neurons (Idoux et al 2006), into genuine type A without oscillations (n ϭ 4/18) or type D with subthreshold oscillations (n ϭ 14/18). No oscillatory cells were found, under control conditions, in type B-like neurons, which will therefore be designated type B.…”

“…2A, inset). In each compartment, in addition to the capacitor and the leak conductance representing the passive properties of the membrane, three voltage-dependent conductances were added: a slow potassium conductance, a g NaP , and a conductance responsible for an h-current (Idoux et al 2006). For each cell, the fit was used to quantitatively determine the electrotonic structure of the neuron, the parameters of the conductances (see Table A1 in APPENDIX A), and the effect of riluzole on the endogenous g NaP .…”

“…In our previous studies (Idoux et al 2006;Serafin et al 1991), the existence of a persistent sodium conductance (g NaP ) in the cell was assessed by detecting the presence or absence of a plateau potential triggered by a short subthreshold pulse. Discrete WN voltage-clamp measurements indicate that g NaP is actually present in all neurons, in contrast to the "plateau method," which fails to detect it in 30% of the neurons (Յ43% for type D).…”

“…Neurons of each cell type differ in their location, shape of the interspike interval, voltage-dependent filter properties, and response to neuromodulation. Furthermore, both experimental data (Rekling and Laursen 1989) and realistic cell models with active dendritic conductances suggest a significant involvement of the persistent sodium conductance (g NaP ) in determining the cell discharge pattern (Idoux et al 2006). In addition, DelgadoGarcía et al (2006) demonstrated that stimulation of saccadic afferents from excitatory burst neurons projecting on type B PHN neurons can trigger sustained activity in the presence of cholinergic agonists.…”

“…Both network and intrinsic properties have been proposed as a substrate for the mechanisms involved in implementing the neural integrator (Major and Tank 2004). An analysis of the intrinsic membrane properties of the PHN neurons (Idoux et al 2006) has shown that there are three cell types in this nucleus (A, B, and D). Neurons of each cell type differ in their location, shape of the interspike interval, voltage-dependent filter properties, and response to neuromodulation.…”