Gaze-stabilizing deficits and latent nystagmus in monkeys with early-onset visual deprivation: role of the pretectal not.

We studied the role of the pretectal nucleus of the optic tract (NOT) in the development of monocular optokinetic nystagmus (OKN) asymmetries and latent nystagmus (LN) in two monkeys reared with binocular deprivation (BD) caused by binocular eyelid suture for either the first 25 or 55 days of life. Single-unit recordings were performed in the right and left NOT of both monkeys at 2-3 yr of age and compared with similar unit recordings in normally reared monkeys. We also examined ocular motor behavior during electrical stimulation of the NOT and during pharmacological inactivation and activation using GABA(A) agonists and antagonists. In BD animals a large proportion of NOT units was dominated by the contralateral eye, in striking contrast to normal animals where 100% of NOT units were sensitive to stimuli delivered to either eye. In the 55-day BD animal no binocularly sensitive neurons were found, while in the 25-day BD animal 60% of NOT units retained at least some binocular sensitivity. Differences in direction sensitivity were also observed in BD animals. We found that 56% of units in the 55-day BD monkey and 10% of units in the 25-day BD monkey responded preferentially to contraversive visual motion. In contrast, only 5% of the NOT units encountered in normally reared monkeys respond preferentially during contraversive visual motion, the rest were most sensitive to ipsiversive visual motion. NOT neurons of BD monkeys showed a wide range of speed sensitivities similar to that of normal monkeys. Unilateral electrical stimulation of the NOT in BD animals induced a conjugate nystagmus with slow phases directed toward the side of stimulation. When we blocked the activity of NOT units with muscimol, a potent GABA(A) agonist, LN was abolished. In contrast, LN was increased when spontaneous activity of the NOT was enhanced with bicuculline, a GABA(A) antagonist. Our results indicate that the NOT in BD monkeys plays an important role in the OKN deficits and LN generation during monocular viewing. We hypothesize that the large proportion of units dominated by the contralateral eye contribute to the development of monocular OKN asymmetries and LN.

The anatomical organization of the macaque pregeniculate complex.

Saccade-related activity recorded in the primate pregeniculate nucleus, and its anatomical connections with the pretectal nucleus of the optic tract (NOT) and superior colliculus (SC), suggest that it plays a role in visual-ocular motor integration. To study this role, a clearer understanding of pregeniculate organization is required. Based on its connectivity and neurotransmitter immunocytochemistry, we demonstrate that this nucleus is composed of several subnuclei, suggesting the term, pregeniculate complex (PrGC). The PrGC includes a weakly developed dorsal lamina, rostrally, and a well-developed ventral lamina. The ventral lamina includes the retinorecipient and superior sublayers, rostrally, and the medial division, caudally. A thin lamina of cells lateral to the dorsal lateral geniculate nucleus is contiguous with the PrGC; we term this the lateral division. The PrGC and the lateral division each project to the SC/NOT; the superior sublayer and medial division of the PrGC are connected reciprocally to the SC/NOT. Immunocytochemistry for gamma-aminobutyric acid (GABA) and substance P (SP) further delineate the PrGC subnuclei. The retinorecipient sublayer stains most intensely for GABA and SP. The superior sublayer and medial division also stain strongly for GABA and SP. Essentially all neurons in the lateral division are GABA-positive. The combination of tract tracing and immunocytochemistry demonstrate differences in the connectivity of the PrGC subnuclei and the lateral division with the SC/NOT. This, combined with the differential localization of GABA in the PrGC, provides a basis for further study of its functional role.

Response of neurons in the dorsal motor nucleus of the vagus to thyrotropin-releasing hormone.

Autonomic motoneurons in the dorsal motor nucleus of the vagus (DMX) were recorded intracellularly in an in vitro slice preparation of the guinea pig brainstem. Bath-applied thyrotropin releasing hormone (TRH) (1-10 microM) induced a reversible depolarization of neurons that was typically accompanied by an increase in the spontaneous firing of the cells. In some cells, TRH induced rhythmic bursting activity. The TRH-induced depolarization occurred also in the presence of reduced Ca2+ and TTX. The response was dose-dependent over TRH concentrations of 0.1-10 microM. The TRH-induced depolarization was accompanied by an increase in input resistance. The reversal potential of this effect corresponded to that of K+. Our results indicate that TRH increases the excitability of DMX neurons by reducing a resting K+ conductance.

Locomotion evoked by stimulation of the brain stem in the Atlantic stingray, Dasyatis sabina.

The primary pathway descending to the spinal cord to initiate locomotion in the stingray is located in the intermediate to ventral portion of the lateral funiculus; a second pathway is located in the dorsolateral funiculus. The goal of this study was to identify the origins of these pathways in the rhombencephalic reticular formation (RF). To do this we used microstimulation of the RF in conjunction with selective lesions of the brain stem and spinal cord. In some animals microinjections of excitatory amino acids were used to avoid stimulating axons of passage. Locomotion in the contralateral pectoral fin was evoked by microstimulation of the dorsal and ventral reticular nuclei, the middle and superior RF, and the ventral portion of the lateral RF. The regions from which locomotion was evoked by chemical stimulation were more restricted and included the rostral dorsal reticular nucleus, the middle RF, and the adjacent ventral lateral RF. This area encompasses the magnocellular RF and coincides with the distribution of numerous reticulospinal cells that project ipsilaterally into the ventral half of the lateral funiculus. Our results indicate, then, that locomotion in the stingray is mediated primarily by a pathway originating in the magnocellular RF that descends ipsilaterally in the ventral half of the lateral funiculus to elicit swimming in the contralateral pectoral fin. We suggest that this primary pathway is specifically associated with the control of locomotion. We also demonstrated that locomotion can be evoked independently from the lateral RF, but is probably mediated by an indirect pathway relaying near the spinomedullary junction or in the rostral spinal cord.

Immunocytochemical localization of GABA in neurons projecting to the ventrolateral nucleus of the solitary tract.

To determine the origin of gamma-aminobutyric acidergic (GABAergic) input to the ventrolateral solitary tract nucleus (vlnTS), we used a double-labeling procedure for retrogradely transported horseradish peroxidase (HRP) and the immunocytochemical localization of GABA. Following HRP injections into the vlnTS, double-labeled neurons were found within the Bötzinger Complex. We conclude that these double-labeled cells are the inhibitory Bötzinger neurons and that GABA is a likely transmitter in this respiratory nucleus.

Tonic descending inhibition in the stingray's spinal cord.

Reflexes elicited by peripheral nerve stimulation were compared in decerebrated stingrays with the spinal cord intact, after a lesion of the dorsal spinal cord and after spinal transection. Reflexes elicited in decerebrated stingrays are tonically inhibited. Lesions of the dorsal spinal cord release this tonic descending inhibition. The tonic descending inhibitory system in stingrays is comparable to that of mammals.

Spinal cord pathways involved in initiation of swimming in the stingray, Dasyatis sabina: spinal cord stimulation and lesions.

In spinally transected stingrays, electrical stimulation of a site just ventral to the dorsal root entry zone or a site in the intermediate portions of the lateral funiculus produced rhythmic swimming like movements of the contralateral pectoral fin. Electromyographic (EMG) records collected during cord-stimulated rhythms had the same pattern of activity and sometimes the same intersegmental coordination as those collected during spontaneous swimming of the same animal. In paralyzed, high-spinal stingrays, the only stimulation sites that produced rhythmic activity (fictive swimming) in the pectoral fin motor nerves were in the intermediate portion of the lateral funiculus. The evoked rhythm occurred in the motor nerves that were contralateral to the stimulated side of the spinal cord. The effects of subtotal lesions of the rostral spinal cord on spontaneous swimming behavior were assessed by analysis of EMG records taken before and after the lesions were made. Severe deficits in swimming occurred after bilateral ablation of intermediate portions of the lateral funiculi. In agreement with previous results, the stimulation experiments indicate that the stingray spinal cord contains an inherent capacity to generate properly coordinated rhythmic swimming. The current experiments also suggest that the descending pathways(s) that normally functions to initiate swimming projects through the intermediate aspects of the lateral funiculi.

The distribution of serotonin in the CNS of an elasmobranch fish: immunocytochemical and biochemical studies in the Atlantic stingray, Dasyatis sabina.

The distribution of serotonin (5HT) in the brain of the Atlantic stingray was studied with peroxidase-antiperoxidase immunocytochemistry and high-pressure liquid chromatography. The regional concentrations of 5HT determined for this stingray fell within the range of values previously reported for fishes. A consistent trend in vertebrates for the hypothalamus and midbrain to have the highest concentrations and the cerebellum the lowest was confirmed in stingrays. Neuronal cell bodies and processes exhibiting 5HT-like immunoreactivity were distributed in variable densities throughout the neuraxis. Ten groups of 5HT cells were described: (I) spinal cord, (II-IV) rhombencephalon, (V, VI) mesencephalon, (VII, VIII) prosencephalon, (IX) pituitary, and (X) retina. There were three noteworthy features of the 5HT system in the Atlantic stingray: (1) 5HT cells were demonstrated in virtually every location in which 5HT-containing cells have been described or alluded to in the previous literature. The demonstration of immunopositive cells in the spinal cord, the retina, and the pars distalis of the pituitary suggests that 5HT may be an intrinsic neurotransmitter (or hormone) in these regions. (2) The distribution of 5HT cells in the brainstem shared many similarities with that in other vertebrates. However, there were many 5HT cells outside of the raphe nuclei, in the lateral tegmentum. It appears that the hypothesis that "lateralization" of the 5HT system is an advanced evolutionary trend cannot be supported. (3) 5HT fibers and terminals were more widely distributed in the Atlantic stingray brain than has been reported for other nonmammalian vertebrates on the basis of histofluorescence. It appears that this feature of the 5HT system arose early in phylogeny, and that the use of immunohistochemistry might reveal a more general occurrence of widespread 5HT fibers and terminals.

Aspects of copulatory behavior and peptide control of egg laying in Aplysia.

The atrial gland of the marine mollusc Aplysia is associated with the large hermaphroditic duct of the reproductive system and contains several peptides capable of inducing egg laying. The structure and function of these peptides are briefly reviewed. It has been hypothesized that during copulation the atrial gland of the female is stimulated by penile insertion to release its peptides, which in turn initiate events leading to egg deposition. To test this hypothesis we monitored reproductive activity over periods of weeks in individual, paired, and grouped A. brasiliana. It was found that copulation is not a necessary stimulus for egg laying, because individually housed Aplysia lay more eggs than when they are paired and allowed to copulate. Nor is copulation a sufficient stimulus, because the vast majority of copulations are not followed by egg laying. Simultaneous egg laying and female copulatory behavior were often observed with grouped and paired animals, but these events are probably not causally related. It is concluded that although the atrial gland contains at least three peptides that can induce egg laying, stimulation of this gland during copulation does not normally serve to initiate egg laying.

Return of axonal and glial membrane specializations during remyelination after tellurium-induced demyelination.

We have studied remyelination of rat peripheral nerves after tellurium-induced demyelination using thin section and freeze-fracture techniques. In rats fed a 1% tellurium diet, regions of demyelination were readily identified by myelin debris and the presence of large denuded axons. Remyelination occurred despite continued tellurium ingestion. However, the demyelinated axons underwent a more rapid remyelination if tellurium was removed from the diet. Remyelination proceeded as described for myelination in the normal developing animal. Sites destined to become nodes of Ranvier were identified as patches of intramembranous particles in the axonal E-face. Early terminal loops of the remyelinating Schwann cell were found adjacent to these particle patches. As wrapping proceeded, terminal loops of myelin, along with associated rows of dimeric-particles characteristic of the axonal P-face, were wound into a paranodal location. This winding of the membrane specializations and associated terminal loops resulted in the reformation of morphologically normal paranodes. The size of the nodal E-face particle patch increased in concordance with increases in the number of paranodal loops until an annulus of particles was obtained as seen in the normal node. The thin section and freeze-fracture morphology of remyelinated fibres was indistinguishable from the morphology of control fibres. These observations are discussed with respect to proposed functions of membrane specializations in myelination and nerve conduction.

Myelination-dependent axonal membrane specializations demonstrated in insufficiently myelinated nerves of the dystrophic mouse.

"Dystrophic' mice of the 129/ReJ-Dy strain have a genetic defect affecting Schwann cell proliferation. Spinal nerve roots of these animals contain myelinated and unmyelinated axons in addition to groups of large "amyelinated' axons. In affected regions of the spinal roots, myelinated axons are missing their myelin sheaths. Where the myelination terminates or begins, half-nodes are created. Freeze-fracture analysis of these half-nodes shows that only the myelinated side contains rows of dimeric particles in the axonal P-face of the paranode. The P-face on the amyelinated side of a half-node, and the remainder of the amyelinated axon. contains a dense even distribution of particles, many of which are the size of dimeric-particle subunits, but only a few of which are arranged into short rows. As the long circumferential rows are not found on the unmyelinated side of the myelinated side of the half-node we conclude that the paranodal rows of dimeric particles are dependent upon myelination for their organization.