Computer-assisted three-dimensional reconstruction and simulations of vestibular macular neural connectivities.

The macular neuroepithelium is morphologically organized as a weighted neural network for parallel distributed processing of information. The network is continuous across the striola, where some type II hair cells synapse with calyces containing type I cells with tufts of opposite directional polarities. Whether other hair cell to calyx appositions that lack synapses interact because of intercellular potassium accumulation remains an open question. A functionally important inference of macular organization is that just as arrays of hair cells communicate an entire piece of information to a nerve fiber, so do macular subarrays of nerve fibers (not single units) carry the whole coded message to the brain stem. Moreover, the size of the network subarray can expand or become more limited depending upon the strength and/or duration of the input. It is the functioning of the network and its subarrays that must be understood if we are to learn how maculas carry out their work and adapt to new environments. Simulations of functioning maculas, or subparts, based on precise morphology and known physiology are useful tools to gain insights into macular information processing. The current simulations of afferent collateral electrical activity are a prelude to development of a 3-D model. The simulations demonstrate a relationship between geometry and function, with the diameter of the stem apparently being a major determinant of electrical activity transmitted to the base in the case of collaterals with short stems. Thus, while changes in synaptic number and/or size may be an important adaptive mechanism in an altered g environment, changes in diameter of the stem is another means of altering outflow. Research on the effects of microgravity should be extremely useful in examining the validity of this and other concepts of neural adaptation, since maculas are biological linear accelerometers ideally suited to the task. Maculas are also extremely interesting to study in detail because of the richness of connectivities and submicroscopic organization they present. Many of their features are common with more complex parts of the brain. It seems possible that knowledge of the three-dimensional geometric relationships operative in a functioning macula will contribute much to the understanding of the dynamics underlying more complex behavior. Computerized approaches greatly facilitate this task and provide an objective method of analysis. It is likely that, in the end, simple rules will be found to govern optimal neural architectural organization, even at higher cognitive levels. The architecture only appears complex because we do not yet grasp its meaning.(ABSTRACT TRUNCATED AT 400 WORDS)

Compartmental modeling of rat macular primary afferents from three-dimensional reconstructions of transmission electron micrographs of serial sections.

1. We cut serial sections through the medial part of the rat vestibular macula for transmission electron microscopic (TEM) examination, computer-assisted three-dimensional (3-D) reconstruction, and compartmental modeling. The ultrastructural research showed that many primary vestibular neurons have an unmyelinated segment, often branched, that extends between the heminode [putative site of the spike initiation zone (SIZ)] and the expanded terminal(s) (calyx, calyces). These segments, termed the neuron branches, and the calyces frequently have spinelike processes of various dimensions that morphologically are afferent, efferent, or reciprocal to other macular neural elements. The purpose of this research was to determine whether morphometric data obtained ultrastructurally were essential to compartmental models [i.e., they influenced action potential (AP) generation, latency, or amplitude] or whether afferent parts could be collapsed into more simple units without markedly affecting results. We used the compartmental modeling program NEURON for this research. 2. In the first set of simulations we studied the relative importance of small variations in process morphology on distant depolarization. A process was placed midway along an isolated piece of a passive neuron branch. The dimensions of the four processes corresponded to actual processes in the serial sections. A synapse, placed on the head of each process, was activated and depolarization was recorded at the end of the neuron branch. When we used 5 nS synaptic conductance, depolarization varied by 3 mV. In a systematic study over a representative range of stem dimensions, depolarization varied by 15.7 mV. Smaller conductances produced smaller effects. Increasing membrane resistivity from 5,000 to 50,000 omega cm2 had no significant effect. 3. In a second series of simulations, using whole primary afferents, we examined the combined effects of process location and afferent morphology on depolarization magnitude and latency, and the effect of activating synapses individually or simultaneously. Process location affects peak latency and voltage recorded at the heminode. A synapse on a calyceal process produced < or = 8% more depolarization and a 23% increase in peak latency compared with a synapse on a process of a neuron branch. For whole primary afferents, depolarization decreased 40% between simulations of the smallest and largest afferents. Simulations in which membrane resistivity and synaptic conductance were varied while afferent geometry was kept constant indicated that use of 5,000 omega cm2 and 1.0 nS produced results that best fit electrophysiological findings. Synaptic inputs activated simultaneously did not sum linearly at the heminode. Total depolarization was approximately 14% less than a simple summation of responses of synapses activated one at a time.(ABSTRACT TRUNCATED AT 400 WORDS)