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Central generation of swimming activity in the hydrozoan jellyfish Aequorea aequorea.

Swimming in Aequorea is controlled by a network of electrically coupled neurons (swim motorneurons) located in the inner nerve ring. The network is made up of the largest neurons in the ring, up to 22 microns in diameter. Intracellular recordings from swim motorneurons reveal slow membrane potential oscillations and a superimposed barrage of synaptic "noise." The synaptic noise, but not the slow oscillations, is eliminated in seawater containing an elevated Mg++ concentration. The swim motorneurons produce a rapid burst of two to eight action potentials preceding each contraction of the subumbrella. Spontaneous bursting persists in high-Mg++ seawater. Injected ramp currents indicated a "bursty" character of the swim motorneurons as suprathreshold depolarizations produced repetitive bursting with an increasing burst frequency with increased depolarization. Hyperpolarizing currents locally blocked spiking in swim motorneurons. Intercellular coupling was demonstrated with Lucifer Yellow injection and dual electrode recordings. In dye fills, only the large neurons of the inner nerve ring were dye-coupled. Two pieces of evidence suggest that swim motorneurons activate the overlying epithelial cells via chemical synapses. First, direct synaptic connections have been noted in ultrastructural examination of the inner nerve ring region. Second, dual recordings from a swim motorneuron and an epithelial cell reveal a 1:1 correspondence between neuron spikes and epithelial synaptic potentials. The synaptic potentials occur with a latency as short as 3 ms which is constant in any one recording session. The results suggest that the swim motorneuron network of Aequorea not only performs a motorneuron function, but also serves as the pattern generator for swimming activity.

Animals↗

Reciprocal changes of excitability between tibialis anterior and soleus during the sit-to-stand movement.

The excitability of spinal motoneurons is modified by central preparatory commands before muscle activation. In relatively complex long duration motor tasks such as the sit-to-stand (STS) movement, the central nervous system commands have to take into account the inputs from muscle, skin, and joint afferents during muscle contraction. We have investigated the changes occurring in tibialis anterior (TA) and soleus (SOL) motoneuronal excitability prior to and during the STS movement in normal subjects. Twelve healthy volunteers received the instruction to rise from a chair at the perception of an acoustic 'go' signal. Cortical transcranial magnetic stimuli (TMS) or peripheral nerve electrical stimuli (PNS) were used as test stimuli to elicit, respectively, the motor evoked potential (MEP) and the H reflex, at intervals of 50-1500 ms after the 'go' signal. Both the MEP and the H reflex were enhanced in the TA between 100 and 900 ms after the 'go' signal. At the same time there was inhibition of the H reflex but not of the MEP in the SOL. At the end of the STS movement, during quiet standing, the size of both the H reflex and the MEP of the TA were not different from those obtained in the sitting position. However, in SOL, the H reflex was smaller, and the MEP was larger, than at rest. Our observations suggest the participation of several mechanisms of control of motoneuronal excitability during the STS, ultimately leading to a dominant role of presynaptic inhibitory mechanisms in SOL during standing.

Adult↗

Characterizing function-structure relationships in the human visual system with functional MRI and diffusion tensor imaging.

A key objective in neuroscience is to improve our understanding of the relationship between brain function and structure. We investigated this in the posterior visual pathways of healthy volunteers by applying functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) with tractography. The optic radiations were segmented using the Probabilistic Index of Connectivity (PICo) tractography algorithm and extracted at several thresholds of connection confidence. The mean fractional anisotropy (FA) of the estimated tracts was found to correlate significantly with fMRI measures of visual cortex activity (induced by a photic stimulation paradigm). The results support the hypothesis that the visual cortical fMRI response is constrained by the external anatomical connections of the subserving optic radiations.

Adult↗

Identification of the spinal neural network involved in coordination of micturition in the male cat.

In these studies, we used the expression of Fos protein to identify cells within the spinal cord that regulate micturition in male cats. The immediate early gene c-fos that encodes the Fos protein can be induced rapidly and transiently in neurons by increased electrical activity. Animals were anesthetized with alpha-chloralose, and received one of four stimulus protocols: electrical stimulation of the pelvic nerve, electrical stimulation of the pudendal nerve, a period of isometric micturition (induced by ligating the proximal urethra and infusing saline into the bladder), or electrical stimulation of Barrington's nucleus. After the period of stimulation, the animals were perfused and neurons expressing Fos-like immunoreactivity (FLI) were visualized with immunocytochemical methods. Stimulation with each protocol resulted in a substantially larger number of neurons expressing FLI than in operated but unstimulated controls, which exhibited few Fos-positive neurons localized to the superficial dorsal horn. In animals undergoing isometric micturition or stimulation of Barrington's nucleus, neurons exhibiting FLI were found bilaterally in the sacral (S1-S3) spinal cord and were localized to the lateral portion of the superficial dorsal horn (laminae I and II), in the intermediolateral region (lateral laminae V-VII), and around the central canal (lamina X and medial laminae V-VII). The intermediolateral region appeared to contain two populations of cells exhibiting FLI: a group of large multipolar cells and a group of small round cells. Few Fos-immunoreactive nuclei were observed in the medial portion of the superficial dorsal horn, and FLI was not observed in ventral horn neurons. Electrical stimulation of the pudendal or pelvic nerves resulted in fewer numbers of cells exhibiting FLI, with a less widespread spatial distribution. These results identify spinal neurons that are active during the micturition cycle, and demonstrate that a behaviorally relevant stimulus (isometric micturition) generated more widespread and greater intensity of Fos expression than repetitive electrical stimulation of the component peripheral nerves.

Animals↗

Intracellular signal modulation: a pivotal role for protein kinase C.

1. Protein Kinase C represents a family of Ca(2+)- and phospholipid-dependent enzymes which catalyzes the covalent transfer of phosphate from ATP to serine and threonine residues on proteins. Phosphorylation of the substrate protein induces a conformational change and thereby a modification of its functional properties. 2. PKC family consists of at least twelve members, divided in three subgroups:classical PKCs, (alpha, beta I, beta II, gamma), new PKCs, (delta, epsilon, eta, theta, mu) and atypical PKCs, (zeta, lambda, iota). The three subgroups differ in cofactors requirements and tissue expression; these differences in co-activators dependency and regional distribution account for the differential activation profile of the various PKC isoenzymes. 3. Different molecules involved in the intracellular signaling network are phosphorylated "in vitro" and "in vivo" by PKC. Many target proteins show a preferential pattern of phosphorylation by the different PKC isotypes. 4. Through phosphorylation PKC modulates the functional activity of many different intracellular signaling systems which transport extracellular messages from the membrane to the nucleus. 5. The induction of apoptotic processes by the protein kinase inhibitor staurosporine indicates a possible role for PKC in the modulation of the intracellular mechanisms leading to Programmed Cell Death. 6. Abnormalities in both levels and activity of PKC, recently found in some chronic neurodegenerative syndromes, lead to the possibility that PKC dysfunction could be involved in the pathogenetic mechanisms of disease.

Amyotrophic Lateral Sclerosis↗

Subcortical connections of visual areas MST and FST in macaques.

To examine the subcortical connections of the medial superior temporal and fundus of the superior temporal visual areas (MST and FST, respectively), we injected anterograde and retrograde tracers into 16 physiologically identified sites within the two areas in seven macaque monkeys. The subcortical connections of MST and FST were found to be very similar. Both areas were found to be reciprocally connected with the pulvinar, mainly with its medial subdivision, and with the claustrum. Nonreciprocal projections from both MST and FST were consistently found in the striatum (caudate and putamen), reticular nucleus of the thalamus, and the pontine nuclei. The labeled terminals in the pons were in the dorsolateral, lateral, dorsal, and peduncular nuclei. Additional nonreciprocal projections were found in one MST and one FST case to the nucleus of the optic tract, and, in one FST case, to the lateral terminal nucleus. Finally, three cases showed a nonreciprocal projection to FST from the basal forebrain. The subcortical structures containing label following MST and FST injections were largely the same as those labeled after injections of the middle temporal visual area (MT), but the label within each structure after MST and FST injections was more widespread than that from MT, overlapping the distribution of label that has been reported after injections of parietal visual areas. This finding is consistent with the known contributions of MST and FST to the functions of parietal cortex, such as eye-movement control.

Animals↗

The murine neurokinin NK1 receptor gene contributes to the adult hypoxic facilitation of ventilation.

Substance P and neurokinin-1 receptors (NK1) modulate the respiratory activity and are expressed early during development. We tested the hypothesis that NK1 receptors are involved in prenatal development of the respiratory network by comparing the resting respiratory activity and the respiratory response to hypoxia of control mice and mutant mice lacking the NK1 receptor (NK1-/-). In vitro and in vivo experiments were conducted on neonatal, young and adult mice from wild-type and NK1-/- strains. In the wild strain, immunohistological, pharmacological and electrophysiological studies showed that NK1 receptors were expressed within medullary respiratory areas prior to birth and that their activation at birth modulated central respiratory activity and the membrane properties of phrenic motoneurons. Both the membrane properties of phrenic motoneurons and the respiratory activity generated in vitro by brainstem-spinal cord preparation from NK1-/- neonate mice were similar to that from the wild strain. In addition, in vivo ventilation recordings by plethysmography did not reveal interstrain differences in resting breathing parameters. The facilitation of ventilation by short-lasting hypoxia was similar in wild and NK1-/- neonates but was significantly weaker in adult NK1-/- mice. Results demonstrate that NK1 receptors do appear to be necessary for a normal respiratory response to short-lasting hypoxia in the adult. However, NK1 receptors are not obligatory for the prenatal development of the respiratory network, for the production of the rhythm, or for the regulation of breathing by short-lasting hypoxia in neonates.

Action Potentials↗

Multineuronal codes in retinal signaling.

The visual world is presented to the brain through patterns of action potentials in the population of optic nerve fibers. Single-neuron recordings show that each retinal ganglion cell has a spatially restricted receptive field, a limited integration time, and a characteristic spectral sensitivity. Collectively, these response properties define the visual message conveyed by that neuron's action potentials. Since the size of the optic nerve is strictly constrained, one expects the retina to generate a highly efficient representation of the visual scene. By contrast, the receptive fields of nearby ganglion cells often overlap, suggesting great redundancy among the retinal output signals. Recent multineuron recordings may help resolve this paradox. They reveal concerted firing patterns among ganglion cells, in which small groups of nearby neurons fire synchronously with delays of only a few milliseconds. As there are many more such firing patterns than ganglion cells, such a distributed code might allow the retina to compress a large number of distinct visual messages into a small number of optic nerve fibers. This paper will review the evidence for a distributed coding scheme in the retinal output. The performance limits of such codes are analyzed with simple examples, illustrating that they allow a powerful trade-off between spatial and temporal resolution.

Action Potentials↗

Morphology of corneal nerves using confocal microscopy.

PURPOSE: The aim of the current study was to evaluate the distribution and morphology of corneal nerves as seen by means of white light confocal microscopy. METHODS: This study analyzed images of corneal nerves that were obtained using the Tomey Confoscan slit scanning confocal microscope (40x/0.75 objective lens). The images were classified according to their location within the cornea. The objective and subjective evaluation of the images involved measuring, grading, or judging a number of parameters from both individual pictures and from each single nerve fiber within any image. RESULTS: The in vivo observations made in this work are in agreement with those of previous histologic studies. The general scheme of corneal innervation is described as originating from thick and straight stromal nerve trunks that extend lateral and anteriorly and give rise to plexiform arrangements of progressively thinner nerve fibers at several levels within the stroma. From there, nerve fibers perforate Bowman's layer and eventually form a dense neural plexus just beneath the basal epithelial cell layer, which is characterized by tortuous and thin beaded nerve fibers interconnected by numerous nerve elements; nerve fibers from this plexus are known to be responsible for the innervation of the epithelium. CONCLUSION: This study provides convincing evidence of the suitability of confocal microscopy to image corneal nerves, the only drawback being the limited resolution in terms of the differentiation of the ultrastructure of nerve bundles.

Adult↗

Optic nerve signals in a neuromorphic chip I: Outer and inner retina models.

We present a novel model for the mammalian retina and analyze its behavior. Our outer retina model performs bandpass spatiotemporal filtering. It is comprised of two reciprocally connected resistive grids that model the cone and horizontal cell syncytia. We show analytically that its sensitivity is proportional to the space-constant-ratio of the two grids while its half-max response is set by the local average intensity. Thus, this outer retina model realizes luminance adaptation. Our inner retina model performs high-pass temporal filtering. It features slow negative feedback whose strength is modulated by a locally computed measure of temporal contrast, modeling two kinds of amacrine cells, one narrow-field, the other wide-field. We show analytically that, when the input is spectrally pure, the corner-frequency tracks the input frequency. But when the input is broadband, the corner frequency is proportional to contrast. Thus, this inner retina model realizes temporal frequency adaptation as well as contrast gain control. We present CMOS circuit designs for our retina model in this paper as well. Experimental measurements from the fabricated chip, and validation of our analytical results, are presented in the companion paper [Zaghloul and Boahen (2004)].

Action Potentials↗

Optic nerve signals in a neuromorphic chip II: Testing and results.

Seeking to match the brain's computational efficiency, we draw inspiration from its neural circuits. To model the four main output (ganglion) cell types found in the retina, we morphed outer and inner retina circuits into a 96 x 60-photoreceptor, 3.5 x 3.3 mm2, 0.35 microm-CMOS chip. Our retinomorphic chip produces spike trains for 3600 ganglion cells (GCs), and consumes 62.7 mW at 45 spikes/s/GC. This chip, which is the first silicon retina to successfully model inner retina circuitry, approaches the spatial density of the retina. We present experimental measurements showing that the chip's subthreshold current-mode circuits realize luminance adaptation, bandpass spatiotemporal filtering, temporal adaptation and contrast gain control. The four different GC outputs produced by our chip encode light onset or offset in a sustained or transient fashion, producing a quadrature-like representation. The retinomorphic chip's circuit design is described in a companion paper [Zaghloul and Boahen (2004)].

Action Potentials↗

The mammalian auditory hair cell: a simple electric circuit model.

A model based on the potassium current pathway through the hair cell is used to analyze the electrical behavior of mammalian inner and outer hair cells. Without taking into account the effects of calcium it is possible to simulate experimental results concerning the shape and strength of the receptor potential and the frequency dependent ac (alternating current) and dc (direct current) components of the receptor current. This model and a simplified form of it are utilized to explain: (1) Transduction latencies: that the receptor potential follows a stimulating signal with a very short delay, under the assumption of a constant number of open K+ channels in the lateral part of the cell membrane. (2) Transduction gains: why higher potential changes are measured in inner hair cells than in outer hair cells, although the outer hair cells are expected to be exposed to higher stereociliary motions: in inner hair cells a decrease in the conductance of the basolateral membrane causes higher gain (receptor potential increases) and together with an increase of membrane capacitance slower reaction (a larger time constant). (3) Transduction channel kinetics: that the shortest (0.1 ms) as well as the longest (20 ms) possible open times of the transduction channels in the stereocilia have different frequency related effects on the shape of the receptor potentials.

Animals↗

Early postnatal development of visual function in ganglion cells of the cat retina.

1. Spontaneous and visually evoked action potentials were recorded from single retinal ganglion cells in superfused retina-eyecups prepared from cats between postnatal day 5 (P5) and adulthood. The development of functional responses was studied quantitatively with contrast-modulated spots and sinusoidal grating stimuli. Some functionally characterized cells were impaled and injected intracellularly with horseradish peroxidase to permit direct structure-function comparisons during the period of synaptogenesis and the expression of transient morphological features. 2. Around the time of eye opening at postnatal day 7-postnatal day 10, the spontaneous discharge of ganglion cells was characterized by bursts of action potentials separated by periods of no activity lasting up to tens of seconds. This "burst-type" pattern gradually changed to a more regular spontaneous discharge during the first 2-3 postnatal wk. The burst-type discharge was completely blocked by 10 mM Mg2+, but was largely unaffected by bath application the excitatory amino acid receptor antagonist 6-cyano-7-nitroquinoxaline-2,3- dione at concentrations that eliminated both spontaneous and light-driven activity of cells that had developed a regular spontaneous discharge. DL-2-amino-7-phosphonoheptanoic acid, a competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, also had little effect on the burst-type discharge but did block the depolarizing effects of exogenous NMDA. These results demonstrate that the burst-type spontaneous discharge is a calcium-dependent process but probably is not mediated by synapses utilizing receptors for excitatory amino acids. 3. On P5, a minority of ganglion cells responded to a light stimulus delivered to the retina at the electrode tip. The percentage of responsive cells increased over time so that all cells responded by P10. During this transition period, the light responses were often weak, fatigued with repeated stimulation, and displayed poor temporal resolution. There was a rapid increase in the briskness of the response to a standard light stimulus during the second through fourth postnatal weeks. However, cells that responded sluggishly to visual stimulation were observed at all ages studied. 4. Both ON- and OFF-type receptive field (RF) centers were observed in approximately equal numbers as soon as the light response developed, and the proportion of the two types was independent of age. Three percent (10/342) of visually responsive ganglion cells had ON-OFF RFs, and the incidence of this type also appeared to be invariant with age.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Defense reaction in the pond snail Planorbis corneus. I. Activity of the shell-moving and respiratory systems.

1. In the intact pond snail Planorbis corneus, tactile or electrical stimulation of the skin evoked a biphasic general defense reaction. A weak stimulation evoked only the first phase of the reaction, represented as a fast pulling of the shell towards the head. With stronger stimulation, this phase was followed by the second phase that was comprised of three components: detachment from the substrate, slow retraction of the body into the shell, and letting out of air from the lung through the pneumostome. 2. About 70 motor neurons (MNs) of the columellar muscle have been revealed in different ganglia by means of their cobalt back-filling through the cut columellar nerve. A complicated pattern of electrical coupling was found for different groups of MNs. Excitation of individual MNs, evoked by current injection, resulted in contraction of the columellar muscle (CNS-columellar muscle preparation). The strongest contraction was evoked by the cerebral MNs; fast small contraction by the parietal MNs; and slow, long-latency contraction, by the pedal MNs. 3. In the same preparation, electrical stimulation of the cutaneous (lip) nerve evoked biphasic contraction of the columellar muscle (a first phase lasting approximately 3 s, and a second phase of up to 1 min). The temporal pattern of this response was similar to that of the defense reaction in the intact animal. A weak stimulation evoked only the first phases of the reaction, while a stronger stimulation evoked both phases. The amplitude of both the first and the second phase was graded with the strength of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Defense reaction in the pond snail Planorbis corneus. II. Central pattern generator.

1. In the isolated CNS of the pond snail Planorbis corneus, spontaneous bursts of activity in the motor neurons (MNs) supplying the columellar muscle were occasionally observed. The biphasic pattern of this activity, with a shorter (3-5 s) initial burst and longer (20-40 s) subsequent burst, was similar to that of the motor output during the general ("whole-body") defense reaction. In preparations consisting of the CNS isolated with the columellar muscle or with the lung, spontaneous biphasic contractions of the muscle as well as openings of the pneumostome with a temporal pattern characteristic of the defense reaction were observed. These findings demonstrated that the efferent pattern of the defense reaction in the snail is, to a large extent, produced by a special neuronal mechanism (the central pattern generator, CPG) triggered by the sensory input, rather than generated by ongoing processing of sensory input. The CPG consists of two components responsible for generation of two phases of the defense reaction. A characteristic feature of the CPG is that the magnitude of its response depends in a graded fashion on the strength of the initial stimulus. 2. In the pleural ganglia there are at least two electrically connected interneurons (DRN1s) that play an important role in generation of the first phase of the defense reaction. Processes of the DRN1s form a ring passing through all (except pedal and buccal) ganglia. The DRN1s received an excitatory input when a peripheral nerve was stimulated. They generated action potentials of long (0.2-2 s) duration. The DRN1 from the right ganglion was studied in more detail.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

The retinal dopamine network alters the adaptational properties of retinal ganglion cells in the cat.

1. Single-unit extracellular recordings of optic tract fibers were used to study ganglion cell (GC) response properties of the intact cat eye before and after the intravitreal injection of haloperidol or SCH23390, dopamine-specific antagonists. Nearly all of the dopaminergic cells in the cat retina are amacrine cells (ACs); thus the dopamine antagonists are thought to primarily block the postsynaptic effects of these dopaminergic amacrine cells. All GCs encountered were subjected to a battery of receptive-field (RF) tests, including classification as X or Y, and as ON or OFF. 2. The effects of haloperidol were greatest in the light-adapted OFF-center pathways and especially in the OFF-center Y-cell. Within 30 min of haloperidol injection, both the spontaneous and light-evoked activity of the OFF-center Y-cell fell to zero, but when the same cell was exposed to lower levels of steady-state background illumination (scotopic levels), the response of the cell once again became robust. 3. OFF-Center Y-cells that had partially recovered from the drug effects and OFF-center X-cells recorded when the drug effect was maximal both possessed intensity-response curves that were shifted to the right of normal. 4. Recovery from the drug effects reflect supranormal responses after the initial response reductions and may be due to haloperidol's action on the dopamine autoreceptor. 5. Of the ON-center cells, only the Y-cells showed response alterations; possessing higher spontaneous activities and slightly reduced amplitudes to RF center (RFC) illumination. 6. The effects of SCH23390 paralleled those of haloperidol except that the onset was faster and the duration of the action of SCH23390 was much shorter, and no supranormal responses followed the initial effects. 7. Dark-adaptation functions of OFF-center GCs revealed a normal rod-cone shift; however, SCH23390 eliminated the rod-cone break, and threshold quickly fell to that of the rod mechanism. 8. The dopaminergic neurons of the cat retina appear to play an important role in regulating the activity of retinal OFF-center pathways in the photopically adapted eye, and one of its functions may be to control the relative contributions of the rod and cone systems to the response properties of light-adapted OFF-center GCs. 9. It is argued that dopamine is released in the light and enhances cone pathway activity, perhaps in the outer retina at bipolar and horizontal cells, and suppresses rod pathway activity, perhaps in the inner retina at amacrine cells.

Adaptation, Ocular↗

Synchronized fast rhythms in inspiratory and expiratory nerve discharges during fictive vocalization.

In precollicular decerebrate and paralyzed cats, respiratory nerve activities were recorded during fictive vocalization (FV), which consisted of a distinctive pattern of 1) decreased inspiratory (I) and expiratory (E) phase durations, 2) marked increase of phrenic activity and moderate changes of recurrent laryngeal (RL) and superior laryngeal (SL) I activities, and 3) massive recruitment of laryngeal and abdominal (ABD; lumbar) E activities. FV was produced by electrical stimulation (100 Hz) in the midbrain periaqueductal gray (PAG) or its putative descending pathways in the ventrolateral pons (VLP). Spectral and correlation analyses revealed three types of effect on fast rhythms during FV. 1) I activities: the coherent high-frequency oscillations in I (I-HFO, 60-90 Hz) present in phrenic and RL discharges during the control state did not change qualitatively, but there was an increase of power and a moderate increase (4-10 Hz) of frequency. Sometimes a distinct relatively weak stimulus-locked rhythm appeared. 2) RL and SL activities during E: in recruited discharges, a prominent intrinsic rhythm (coherent E-HFOs at 50-70 Hz) appeared; sometimes a distinct relatively strong stimulus-locked rhythm appeared. 3) ABD activities during E: this recruited activity had no intrinsic rhythm but had an evoked oscillation locked to the stimulus frequency. Thus FV is characterized by 1) appearance of prominent coherent intrinsic rhythms in RL and SL E discharges, which presumably arise as a result of excitation and increased interactions in laryngeal networks; 2) modification of intrinsic rhythmic interactions in inspiratory networks; and 3) evoked rhythms in augmenting-E neuron networks without occurrence of intrinsic rhythms.

Anesthesia↗

Mapping of the normal human corneal sub-Basal nerve plexus by in vivo laser scanning confocal microscopy.

PURPOSE: To produce a two-dimensional reconstruction map of the living human sub-basal corneal nerve plexus using in vivo confocal microscopy. METHODS: Laser scanning in vivo confocal microscopy was performed on three normal eyes of three healthy human subjects. Subjects were asked to fixate on targets arranged in a grid to enable examination of the cornea in a wide range of positions. Using the section mode, a mean of 573 +/- 176 images of the sub-basal plexus were obtained for each subject. The data were arranged and images were mapped for each subject into confluent montages. RESULTS: Mean dimensions of the corneal areas mapped were 4.95 +/- 0.53 mm horizontally and 5.14 +/- 0.53 mm vertically. In all subjects, the sub-basal nerve plexus appeared to radiate toward a whorl-like complex centered 1 to 2 mm inferior to the corneal apex. Outside this area, the nerve fiber bundles in the remainder of the cornea were arranged in a radiating pattern. Mean nerve density was significantly higher in the inferocentral whorl region (25,249 +/- 616 microm/mm2) compared with the central cornea (21,668 +/- 1411 microm/mm2) (Mann-Whitney U test; P = 0.05). CONCLUSIONS: This is the first study to elucidate the overall distribution of sub-basal nerves in the healthy, live central to mid-peripheral human cornea by laser scanning in vivo confocal microscopy. The whorl pattern of the sub-basal nerves is similar to that seen in the epithelium in corneal verticillata and may lend support to the theory that epithelial cells and nerves migrate centripetally in tandem.

Adult↗