Representation of whisker follicle intrinsic musculature in the facial motor nucleus of the rat.

Retrograde transport of wheatgerm-agglutinin horseradish peroxidase (WGA-HRP) and fluorescent tracers (true blue-TB, nuclear yellow-NY, and diamidino yellow-DY) from isolated whisker follicles was used to define the somatotopic organization of the facial (VII) motoneurons which innervate the intrinsic follicle muscles. Motoneurons supplying these muscles were restricted almost completely to the lateral (Martin and Lodge, '77) facial subnucleus and the motoneurons which innervated a given follicle were distributed over the entire length of this subnucleus. Cells projecting to dorsal (A-row) follicles were located in the most lateral part of the lateral subnucleus, while those supplying ventral (E-row) follicles were restricted to the medial part of the subnucleus. Injections of different tracers into rostral and caudal follicles within a given row revealed no somatotopic representation of the rostrocaudal axis of the whiskerpad. Additional control experiments demonstrated that some of the labelling obtained with WGA-HRP resulted from spread of this tracer to extrinsic muscles. This was not the case with the fluorescent tracers. The results of the control experiments suggested further that a significant percentage of the motoneurons in the lateral facial subnucleus innervate only intrinsic follicle muscles.

Afferents to the trigeminal and facial motor nuclei in pigeon (Columba livia L.): central connections of jaw motoneurons.

Trigeminal and facial motor nuclei innervating the pigeon's jaw muscles were identified using a combination of microstimulation and EMG recording and HRP injections were made iontophoretically. The trigeminal motor nucleus receives an ipsilateral projection from sensory neurons in the trigeminal mesencephalic nucleus which forms the afferent limb of the monosynaptic stretch reflex of the jaw-closers. Both the trigeminal and facial motor nuclei receive bilateral projections from interneurons in the intertrigeminal area and the lateral (parvocellular) reticular formation of the pons and medulla. These neurons serve as premotor elements in the control of jaw movements, mediating ascending, descending and internuclear connections. The similarity of inputs to the trigeminal and facial nuclei may reflect their common function as jaw motoneurons in this species.

Structure-function relationships in rat brainstem subnucleus interpolaris. XI. Effects of chronic whisker trimming from birth.

Whisker trimming from birth reduces activity and alters receptive fields (RFs) in the barrel cortex and thalamus. To assess whether or not this reflects deprivation effects on trigeminal (V) first- and second-order neurons, 59 primary afferents and 343 cells in V brainstem subnucleus interpolaris (SpVi) were studied in rats whose whiskers were trimmed daily for 6-9 weeks from birth. Deprivation did not effect brainstem somatotopy or primary afferent RFs. However, many SpVi cells had abnormal RFs and higher-order inputs, resembling the changes caused by infraorbital nerve injury. For example, in controls, only 3% of whisker-sensitive local circuit neurons responded to more than one whisker, whereas 35% of the deprived and 41% of the infraorbital nerve cut samples had multiwhisker. RFs. Deprived rats also had higher than normal incidences of cells with split or absent RFs, RFs spanning more than one V division, intermodality convergence, and directional or high-velocity sensitivity. Because these changes mimic those caused by nerve section, deprivation may underlie some nerve injury effects on V brainstem RF size and character. Insofar as cytochrome oxidase, anterograde labeling, and unit recordings revealed normal topography in deprived primary afferents and SpVi cells, RF changes in SpVi cells may reflect altered SpVi circuitry. To test this hypothesis, we assessed the morphology of 32 similarly deprived V primary afferents. In SpVi, deprived fibers had normal numbers of collaterals with normal shapes, transverse arbor areas, and topography. However, the total number of boutons per collateral was significantly reduced. Thus, deprivation effects on V higher-order RFs reflect quantitative changes in V afferent terminals.

Structural and functional characteristics of commissural neurons in the superior colliculus of the hamster.

Intracellular recording and horseradish peroxidase (HRP) injection techniques were employed to delineate the structural and functional properties of superior collicular (SC) neurons in the hamster that were antidromically activated by electrical stimulation of the contralateral tectum. A total of 39 such cells were completely characterized, injected, and recovered. In ten of these, the axonal filling allowed us to reconstruct at least a portion of the terminal arborization in the SC contralateral to the labelled cell. Two of the recovered neurons were located in the stratum griseum superficiale (SGS), three were in the stratum opticum (SO), ten were in the stratum griseum intermediale (SGI), 11 were in the stratum album intermedium (SAI), 11 were in the stratum griseum profundum (SGP) and two were located in the stratum album profundum (SAP). The recovered cells were highly varied in both their morphological and their physiological characteristics. Somal areas ranged between 74 microns2 and 364 microns2, and the sample of recovered neurons included horizontal cells, narrow field vertical cells, and a variety of other multipolar neurons. Over one-third (38.5%) of the recovered cells were unresponsive, 2.6% were exclusively visual, 33.3% responded only to innocuous cutaneous stimuli, 10.2% were bimodal, 7.7% were specifically nociceptive, and 7.7% had complex (Rhoades, Mooney, and Jacquin: J. Neurosci. 3:1342-1354, '83) somatosensory receptive fields. We observed no clear-cut correlations between the structural and functional characteristics of these neurons. The conduction latencies of the commissural SC neurons ranged between 0.8 and 14.0 ms. The most rapidly conducting cells were located in the SGP and SAP. Conduction latency had a significant negative correlation with soma area. Labelled axons, in many cases, had at least one terminal arbor in a portion of the SC that was mirror symmetric with the location of the cell from which it originated. In several cases, however, commissural axons gave off a number of collaterals across the mediolateral extent of the tectum. commissural axonal terminations were visible only in the laminae ventral to the SO. Several commissural SC neurons also had extensive ipsilateral axon collaterals. Both the ipsilateral and commissural axon branches of these cells gave off en passant and terminal swellings.

Anatomical consequences of neonatal infraorbital nerve transection upon the trigeminal ganglion and vibrissa follicle nerves in the adult rat.

A large body of experimental literature has demonstrated that neonatal infraorbital nerve damage in rodents produces anatomical and/or functional alterations of the normal whisker representation in central trigeminal structures. Less is known about the organization of primary afferent components of the trigeminal system following this manipulation. Such information provides an important basis for interpreting the central changes observed following damage of infraorbital nerve fibers at birth. We have therefore examined the composition and order of peripheral innervation in the pathway from the trigeminal ganglion to the vibrissa follicles in adult rats subjected to unilateral neonatal infraorbital nerve transection. Electron microscopy was used to determine the number and diameter of myelinated and unmyelinated fibers in vibrissa follicle nerves of these animals. Wheat germ agglutinin-horseradish peroxidase and fluorescent retrograde tracers were employed to examine the number and diameter, as well as the topographic organization and branching, of ganglion cells innervating the vibrissae in these rats. The data presented below indicate that neonatal infraorbital nerve transection has the following consequences within the adult trigeminal nerve and ganglion: 1) an alteration of the gross morphology of vibrissal nerves, 2) a significant reduction in the average number (85.4%) and diameter (32.6%) of myelinated, but not unmyelinated, follicle nerve axons, 3) a significant decrease in the average number (36.8%) of trigeminal ganglion cells innervating vibrissa follicles, 4) no significant change in the distribution of ganglion cell diameters, 5) an increase in peripheral branching (1.8-fold) of these ganglion cell axons, and 6) an alteration of somatotopic order within the trigeminal ganglion. Taken together, these data indicate that neonatal infraorbital nerve transection produces a profound reorganization of the primary afferent component of the trigeminal neuraxis.

Structure-function relationships in the rat brainstem subnucleus interpolaris: VI. Cervical convergence in cells deafferented at birth and a potential primary afferent substrate.

Possible substrates for peripheral injury-induced receptive field (RF) changes were assessed in the trigeminal (V) subnucleus interpolaris (SpVi). In adult rats with infraorbital nerve section at birth, 449 cells were studied ipsilateral to the lesion by using electrophysiological methods. Of these, 33 (7.4%) had RFs that included facial vibrissae, guard hairs, and skin, as well as ipsilateral regions normally innervated by cervical primary afferents (ear, neck, shoulder, arm, forepaw). Such non-V convergence was never seen in 373 normal SpVi cells or in 641 V ganglion cells ipsilateral to the lesion. SpVi cells with cervical RFs discharged to V ganglion shocks and their latencies (1.6 +/- 0.7 ms, mean +/- s.d.) did not differ from normal (1.4 +/- 0.5). Most (71%) projected to the thalamus. None were nociceptive-biased, and many had unusually discontinuous RFs (48%). Possible pathways by which cervical inputs might reach SpVi neurons were investigated in additional anatomical and electrophysiological experiments. Eight SpVi cells with cervical RFs were intracellularly labeled with HRP. Although all had dendrites that were polarized toward SpVi regions containing spared mandibular and/or ophthalmic primary afferents, none had dendrites which extended out of SpVi. In other neonatally nerve-damaged adults, WGA-HRP was injected bilaterally into forepaw, arm, and shoulder regions. Transganglionic transport was restricted to normal targets. However, WGA-HRP injections into SpVi retrogradely labeled a total of 46 +/- 20 (mean +/- s.d.) cells in ipsilateral C1-3 dorsal root ganglia, and 24 +/- 8 cells in C4-8 ganglia. In controls, labeled cells were seen only in C1-3 ganglia (32 +/- 9). The distribution and number of labeled cells in the somatosensory cortex did not differ in experimental and control cases. No labeled cells were visible in the dorsal column nuclei of either the normal or experimental rats. Thus, retrograde labeling studies suggest that a cervical primary afferent projection to SpVi is a potential substrate for cervical convergence expressed in neonatally deafferented SpVi cells.

The structural and functional characteristics of tectospinal neurons in the golden hamster.

Intracellular recording and horseradish peroxidase (HRP) injection techniques were used to delineate the structural and functional characteristics of the superior collicular cells in the hamster, which could be antidromically activated from the first cervical segment of the spinal cord. Thirty-one such neurons were characterized, filled with HRP, and recovered. Complete physiological data were obtained from another 21 tectospinal cells for which anatomical data were sufficient only to define the laminar location of the cell body from which recordings were made. Of the total sample of 52 cells, 7.7% had their somata in the stratum griseum intermediale (SGI), 50% were in the stratum album intermedium (SAI), 36.5% were in the stratum griseum profundum (SGP), and 5.8% were in the stratum album profundum (SAP). The tectospinal cells were fairly uniform morphologically. They had large (27.7 +/- 5.5 microns diameter) cell bodies, which gave rise to an average of 6.7 +/- 1.2 primary dendrites. These were generally smooth and extended up to 500 microns away from the cell body. In many cases, they ascended out of the deep laminae into the stratum opticum (SO) and/or stratum griseum superficiale (SGS). The axons of TS cells averaged 3.4 +/- 0.8 microns in diameter, and they generally coursed radially to the SAP where they curved around the periaqueductal gray and entered the predorsal bundle. These axons often gave rise to collaterals that arborized in the deep laminae of the ipsilateral superior colliculus and subjacent reticular formation. The tectospinal cells were also fairly uniform physiologically. Their average conduction latency was 2.0 +/- 2.3 ms, and this variable had a strong negative correlation (-.81) with axon diameter for the recovered cells. Most (63.5%) of the TS cells were exclusively somatosensory and gave rapidly adapting responses to deflection of vibrissae and/or guard hairs; 7.7% were bimodal (visual-somatosensory); 11.5% had complex (Rhoades et al., '83) somatosensory receptive fields; 1.9% were discharged only by a noxious pinch, and 15.4% were unresponsive. A common feature of all bimodal tectospinal neurons was dendrites that extended at least as far dorsally as the SO. Whereas there were no other clear-cut correlations between the structural and functional characteristics of these tectal neurons, we did note that all of the cells with complex somatosensory receptive fields received inhibitory input from axons that either originated from, or passed through, the contralateral superior colliculus.

Effects of altered visual input upon the development of the visual and somatosensory representations in the hamster's superior colliculus.

The right superior colliculus and right eye were ablated in hamsters within 12 h of birth and the visual and somatosensory representations in the remaining (left) superior colliculus were evaluated using standard single unit recording and receptive field mapping techniques when the animals reached adulthood (at least 3 months of age). In a number of the hamsters used for recording, injections of [3H]leucine were made into the left eye 6-10 days prior to the terminal experiment. This was done to insure that the neonatal lesions did, in fact, produce the extensive recrossing of retinal fibers demonstrated by others who have employed this preparation. All of the hamsters which received [3H]leucine injections prior to the recording experiment exhibited a markedly expanded ipsilateral retinocollicular projection and retinal axons which recrossed the midline at the level of the tectum. The recording experiments showed further that this projection resulted in a visual map which was generally mirror symmetric to that in normal hamsters. There were, however, numerous irregularities and discontinuities in this representation and, in a few hamsters, it appeared almost completely disorganized. There were also a number of abnormalities in the somatosensory representation in the deep tectal laminae of the neonatally brain damaged hamsters. There was a substantial increase in the number of cells with receptive fields that extended onto the ipsilateral side of the body, neurons with split receptive fields were recorded and there were changes in the magnification of different portions of the body surface. These alterations did not, however, change the organization of the somatosensory map in a manner which brought it into alignment with the visual representation in the superficial laminae. Nevertheless, additional recording experiments in animals subjected to enucleation of both eyes and ablation of the superficial laminae of one superior colliculus did indicate that the existence of the aberrant retinal projection was a necessary condition for the somatosensory abnormalities which we observed. Additional anterograde and retrograde tracing experiments demonstrated only one abnormality in the organization of the somatosensory afferent input to the remaining colliculus. In 75% of the brain damaged hamsters, there was a weak crossed projection from the sensorimotor cortex that was never observed in normal animals. Ablation of this cortex at the time of the recording experiment did not, however, reduce the incidence of abnormal somatosensory receptive fields in these hamsters.

The structural and functional characteristics of striate cortical neurons that innervate the superior colliculus and lateral posterior nucleus in hamster.

Intracellular recording and horseradish peroxidase injection techniques were used to structurally and functionally characterize the striate cortical neurons in hamster that projected to the superior colliculus and/or lateral posterior nucleus of the thalamus. With two exceptions, the receptive field properties and morphological characteristics of the neurons antidromically activated from the colliculus and lateral posterior nucleus were quite similar. Striate corticotectal and striate cortico-lateral posterior neurons generally had non-oriented receptive fields which gave either "on-off' or no responses to flashed stimuli. Only a small number (less than 5%) were orientation selective, but about one-third were directionally selective. Most of the cells preferred movement with an upward component. Most striate corticotectal and cortico-lateral posterior cells responded to a wide range of stimulus velocities and exhibited little spatial summation. With the possible exception of two cells, all the projection neurons we recovered were large lamina V pyramidal cells whose apical dendrites extended to and branched extensively in layer I. All had extensive (in some cases over 1 mm) tangential axon collaterals, primarily in layers V and/or VI. The electrophysiological experiments also demonstrated that some (50% of a sample of 20 cells) corticotectal neurons also sent an axon collateral to the lateral posterior nucleus. Finally, our recordings showed that many (56% of a sample of 27 neurons) cells which could be antidromically activated from the lateral posterior nucleus, but not the superior colliculus had response latencies which exceeded those of almost all the cells which could be antidromically activated from the tectum. Retrograde transport of diamidino yellow and true blue confirmed the electrophysiological result that individual cortical neurons projected to both the superior colliculus and lateral posterior nucleus. These experiments showed that 20% of the striate cortical cells that projected into colliculus also sent an axon collateral to the lateral posterior nucleus.

Neonatal infraorbital nerve damage and the development of eating behavior in the rat.

It has been previously shown that bilateral infraorbital nerve (ION) transection in adult rats has little effect upon body weight regulation or eating behavior. However, in neonatal mouse, unilateral ION cut produces a profound decrease in body weight, beginning around the time of weaning. To help clarify the role of the ION in the development and sensorimotor control of eating solid food in rodents, the present experiment examined the effects of unilateral, neonatal ION transection in rats, upon body weight regulation and post-weaning eating behaviors. Comparison of normal and lesioned groups of rats, up to postnatal day (PND) 61, revealed no significant difference in mean adjusted (for sex) body weight. In addition, no significant differences were detected between the groups on post-weaning (PND 26 to PND 61) measures of mean adjusted (for weight) food intake, responsiveness to food, biting ability or inefficiency of mandibulation. At the end of the experiment, the effectiveness of the lesion was histologically evaluated. A significant 48.5% mean reduction in the cross-sectional area of the ophthalmic-maxillary portion of the trigeminal ganglion was observed on the lesioned side, relative to the intact side. There appears to be a differential influence of unilateral, neonatal ION cut upon eating in rat and mouse.

Orofacial pain sensitivity in adult rats following neonatal infraorbital nerve transection.

A modification of the formalin test was used to assess orofacial pain sensitivity in adult rats that received infraorbital nerve transection at birth. Normal and neonatally lesioned adult animals received an injection of either 5% formalin or saline vehicle into the whiskerpad and the duration of whiskerpad rubbing was observed for 45 min. Normal rats given formalin exhibited the previously reported biphasic pattern of rubbing. Neonatally lesioned rats given formalin did not exhibit this pattern, and were indistinguishable from either of the saline control groups.

Grasping in the pigeon (Columba livia): final common path mechanisms.

A combination of cinematographic and denervation procedures were used to analyse the mechanisms involved in the adjustment of gape size during grasping in the pigeon. Gape size was found to vary directly with seed size and to reflect the operation of two variables, jaw opening velocity and jaw opening duration. Effects upon duration are mediated, indirectly, by the effect of seed size upon head height, which, in turn, controls the velocity of head descent. The data suggest that the control of gape during grasping may involve two different effector systems (jaw muscles, neck muscles). Analysis of the displacement of individual jaws (maxilla, mandible) during grasping indicates that both opener muscles take part in the control of gape. Denervation experiments (motor nerve section) identified these opener motoneurons as contributors to the final common path for the opening phase of grasping. A comparison of the kinematics of pecking/grasping in pigeons and reaching/grasping in humans reveals a number of similarities in the topography and spatiotemporal organization of these behaviors.

Biochemical and anatomical consequences of adult infraorbital nerve transection for serotonergic afferents within rat trigeminal subnuclei interpolaris and caudalis.

Immunocytochemistry and high-performance liquid chromatography with electrochemical detection (HPLC-ED) were used, more than 76 days after infraorbital nerve (ION) transection, to examine the distribution and density of serotonin-immunoreactive (5-HTIR) axons, as well as serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content, within the infraorbital (IO) regions of subnuclei caudalis (SpVc) and interpolaris (SpVi). In SpVi, increases in 5-HT concentration and in density of 5-HTIR axonal varicosities were observed on the lesioned side. No changes were seen in SpVc.

Rapid shifts in receptive fields of cells in trigeminal subnucleus interpolaris following infraorbital nerve transection in adult rats.

Transection of the infraorbital nerve in adult rats results in an array of chronic functional anomalies in trigeminal brainstem subnucleus interpolaris, including changes in normal receptive field organization. This work examined whether long-term maintenance of acute modifications, such as unmasking or strengthening of normally ineffective inputs to interpolaris cells, might contribute to the previously described chronic abnormalities. Using glass micropipettes, extracellular isolation of 37 interpolaris cells, with infraorbital receptive fields, was maintained following intraorbital transection of the infraorbital nerve. Receptive fields and dynamic response properties were characterized immediately before and after the cut and throughout the post-transection isolation period. Orthodromic latencies to trigeminal ganglion shocks and antidromic activation from thalamus or cerebellum were also examined. Of the 37 cells, 21.6% exhibited receptive field shifts to non-infraorbital regions after cutting the infraorbital nerve. Using the normal probability of observing an interpolaris cell with more than one trigeminal division in its receptive field, the probability of observing this shift by chance was 0.0013. No such changes were observed for 12 control cells, recorded for durations equal to or greater than total recording times for the shifting cells, with the nerve intact. The representation of local circuit, thalamic-projecting and cerebellar-projecting cells was similar in the total sample; however, all neurons exhibiting transection-induced receptive field shifts were projection neurons. In comparing the sample of cells that exhibited receptive field shifts with those that did not, prior to infraorbital nerve cut, there was no difference in mean latencies and thresholds for activation from the stimulating electrodes or in mean depth at which the cells were isolated. In addition, no difference was evident in receptive field size, effective receptor surface, dynamic response characteristics or spontaneous activity. These data suggest that maintenance of acute receptive field changes, following infraorbital nerve cut, may contribute to some types of chronic functional alterations observed after such damage.

Topographic organization of peripheral trigeminal ganglionic projections in newborn rats.

Retrograde transport of fluorescent tracers (true blue and diamidino yellow) was employed to delineate the topography of the peripheral projections of trigeminal ganglion cells in newborn (less than 12 h of age) rats. Identical injections were made in adult animals for comparison. In neonates, both inter- and intradivisional topography of ganglionic projections were adult-like. Neurons which innervated mandibular fields were located posterolaterally while cells with ophthalmic or maxillary projections were restricted to the anteromedial and central parts of the ganglion, respectively. An adult-like topographic representation of the mystacial vibrissae follicles was also evident in the neonates.

Extensive recrossing of retinotectal axons after neonatal unilateral superior collicular lesions in hamster.

Anterograde transport methods were used to examine the ipsilateral retinocollicular projections of adult hamsters subjected to ablation of one superior colliculus (SC) on the day of birth. In many of these animals ipsilateral retino-SC axons were not limited to the medial part of the remaining tectum as previously reported but encompassed the entire rostrocaudal and mediolateral extents of this SC. A common pattern was the existence of a dense patch of label contiguous with the midline, a more lateral region of diffuse labeling, a second dense lateral patch and diffuse labeling which extended to the lateral boundary of the tectum. The dense patches of label were usually aligned into rostrocaudally oriented bands. Additional experiments in which one optic tract was sectioned a week prior to the eye injection showed that the reorganization was primarily due to axons which recrossed the midline at the level of the midbrain. However, the uncrossed retinotectal projection was also abnormally dense in the animals subjected to neonatal SC lesions. Dense patches of label in the caudal half of the tectum were only observed when recrossing fibers were labeled. In a final set of experiments, both the ipsilateral and contralateral projections were labeled with different tracers in individual hamsters. These experiments showed a clear tendency for fibers from the two eyes to segregate in the remaining SC. This segregation was, however, incomplete, even in regions where labeling from each eye was quite dense.

Renewed growth of identified brainstem axons into fetal cortical transplants in adult rat.

Transplantation of fetal neocortex into the site of trigeminal brainstem injury induces regeneration of trigeminal primary afferent axons in adult rats. Renewed growth of injured primary afferent fibers into donor cortex can be extensive, though the innervation pattern does not resemble that normally seen in either brainstem or somatosensory cortex. Examination of the structural and functional characteristics of individual regenerate axon collaterals suggests that their morphology is determined by both intrinsic and postsynaptic target factors. Marked topographic alterations, however, question the utility of fetal cortical transplantation procedures in effecting functional recovery from brainstem injury.

Time course of serotonergic afferent plasticity within rat spinal trigeminal nucleus following infraorbital nerve transection.

High-performance liquid chromatography with electrochemical detection (HPLC-ED) and immunocytochemistry were used to examine the time course of serotonergic afferent plasticity within trigeminal subnucleus interpolaris (SpVi) following infraorbital nerve (ION) transection in adult rats. Biochemical analysis was also performed in trigeminal subnucleus caudalis (SpVc) to examine the possibility of transient lesion-induced changes in this region. No significant changes in serotonin (5-HT) or 5-hydroxyindoleacetic acid (5-HIAA) concentration, or in density of 5-HT-immunoreactive (5-HTIR) axonal varicosities were observed in either subnucleus on the lesioned side, up to 51 days following ION cut. However, at 76-79 days post-lesion, a significant increase in 5-HT concentration was again demonstrated within SpVi.

Dendrites of deep layer, somatosensory superior collicular neurons extend into the superficial laminae.

Intracellular recording and horseradish peroxidase (HRP) injection techniques were used to delineate the structural and functional properties of superior collicular (SC) neurons in hamsters. Of 34 cells recovered from the deep laminae (those ventral to the stratum opticum--SO), 26 were exclusively somatosensory and 10 of these extended dendrites into the superficial layers, the stratum griseum superficiale (SGS) and SO. In 2 instances, dendrites extended only to the SO, but in 8 others they reached the SGS. Three of the latter cells had dendrites which terminated just beneath the pial surface. These findings show that an anatomical substrate for communication from superficial to deep layer cells exists in the hamster SC, but that such communication may not necessarily be reflected in the response of deep layer neurons.

Pharmacological properties of the MPTP analog trans-1-methyl-4-[4-dimethylaminophenylethenyl]-1,2,3,6-tetrahydropyridine and its pyridinium metabolite in mouse brain synaptosomes: a potential visual marker for substrates of MPTP-induced neurotoxicity.

1. The tetrahydropyridine trans-1-methyl-4-[4-dimethylaminophenylethenyl]-1,2,3,6-tetrahydropyridine (t-THP), like MPTP, can undergo monoamine oxidase (MAO)-mediated conversion to a dihydropyridinium intermediate and subsequent metabolism to a pyridinium species. t-THP is also a better substrate for MAO B than MAO A. In contrast to the metabolism of MPTP, the pyridinium ion derived from t-THP is highly fluorescent. This endows t-THP with potential as an in vivo visual probe for localizing the substrates of MPTP-like neurotoxicity. As a prelude to in vivo labeling studies, we examined the metabolism and uptake kinetics of t-THP and its metabolites in mouse striatal and cortical synaptosomes. 2. T-THP was found to induce a concentration-dependent and saturable fluorescence within striatal and cortical synaptosomes that was also MAO-dependent. Like MPP+, the fluorescent pyridinium ion t-P+, derived from t-THP, inhibited the uptake and facilitated the release of monoamines from synaptosomes in a concentration-dependent fashion. The ion did not rely on sodium-dependent membrane transporters for its concentration-dependent uptake into synaptosomes, although it may have an irreversible affinity for the dopamine transporter. 3. These data suggest that t-THP could be appropriate for use as a visual marker for microenvironments where MPTP-like compounds are taken up and converted to potentially neurotoxic pyridinium species. Such a marker could be employed to address some of the issues regarding the selectivity of MPTP-induced neurotoxicity.