Effects of estrogen on the excitability of neurons projecting from the noradrenergic A1 region to the preoptic and anterior hypothalamic area

Estradiol benzoate administered to ovariectomized female rats significantly elevated the mean spontaneous firing rate and frequency of successful antidromic propagation into the somatodendritic spike and significantly reduced the strength of post-stimulus inhibition in presumed A1 noradrenergic neurons projecting directly to the preoptic and anterior hypothalamic area. The occurrence of both antidromic spikes and post-stimulus inhibition of the majority of these neurons was completely abolished by the injection of 6-hydroxydopamine but not by 5, 7-dihydroxytryptamine directly into the medial forebrain bundle.     

Innervation of embryonic hippocampal implants by regenerating axons of cholinergic septal neurons in the adult rat

The regeneration of the septal cholinergic system in adult rats has been studied in animals bearing transplants of hippocampus taken from 20–40 mm rat fetuses (approximately 17–21 days of gestation). The septal axons located within the fimbria and the dorsal fornix were lesioned and a cavity was prepared at the rostral end of the hippocampus. The embryonic tissue was placed adjacent to the severed end of the fornix-fimbria. The time-course of ingrowth of cholinergic fibers into the transplant was monitored by acetylcholine esterase (AChE) histochemistry and the determination of the levels of choline acetyltransferase (ChAT). Both methods indicate that there is a progressive ingrowth into the transplant of cholinergic fibers up to 3 months after transplantation. The newly-formed AChE-positive fibers in the transplant remain beyond one year after transplantation and are thus presumably permanent. Both horseradish peroxidase (HRP) injections into the implant and radiofrequency lesions of the septal-diagonal band area indicate that the principal source of these fibers is the AChE-positive neurons of the medial septum and the nucleus of the diagonal band which normally form the septohippocampal cholinergic projection. The results suggest: (1) that implants of a normal embryonic target tissue can promote axonal regeneration in mature neurons of the mammalian central nervous system; (2) that some neurons in the adult mammalian CNS retain at least part of their embryonic capacity to generate axons and recognize specific postsynaptic targets in developing CNS tissue; and (3) that this host-implant interaction can result in the formation of quite specific innervation patterns in the implanted target tissue.     

Anatomical evidence for direct fiber projections from the cerebellar nucleus interpositus to rubrospinal neurons. A quantitative EM study in the rat combining anterograde and retrograde intra-axonal tracing methods

A quantitative electron microscopic (EM) study combining the anterograde intra-axonal transport of radioactive amino acids and the retrograde intra-axonal transport of the enzyme horseradish peroxidase (HRP) was performed in the magnocellular red nucleus of the rat to obtain anatomical evidence as to whether there is a direct projection from the cerebellar nucleus interpositus to the cells in the red nucleus that give rise to the rubrospinal tract. Large asymmetrical synaptic terminals were radioactively labeled in the magnocellular red nucleus following injections of [3H]leucine into the cerebellar nucleus interpositus. In these same animals, the postsynaptic target neurons were labeled with HRP granules after injection of this substance in the rubrospinal tract. A quantitative analysis showed that more than 85% of the large and giant neurons in the magnocellular red nucleus were labeled with HRP granules and also received synaptic contacts from radioactively-labeled terminals. Thus, it can be concluded that in the rat, afferents from the cerebellar nucleus interpositus establish asymmetrical synaptic contacts with large and giant rubrospinal neurons, thus confirming and extending the previous physiological evidence of such direct monosynaptic connections.     

Growth zone of the juvenile goldfish retina revealed by fluorescent flat mounts

The retinas of juvenile goldfish (Carassius auratus) were processed for fluorescence microscope studies with flat mounts. The fish were reared in a laboratory aquarium for 1–3 months after either one class of retinal dopaminergic (DA) cells or indoleamine-accumulating (IA) cells had been destroyed by intravitreal injection of 6-hydroxydopamine (6-OHDA; 2.5 m?g) or 5,7-dihydroxytryptamine (5,7-DHT; 2.5 μg). The fish grew 10–12 cm in body length on the average for 3 months. The retinas were isolated at various survival times after pretreatment with 6-OHDA or 5,7-DHT. To improve detection of the cells, a mixture of noradrenaline (NA; 0.5 μg) and 5,6-DHT (0.5 μg) was intravitreally injected into the eyes 2 hr before enucleation. Retinal growth occurred by cell proliferation at the circumferential margin distal to the retinal center. In this process, DA and IA cells were added in concentric rings, with a rate of cell accretion of approximately 12 cells per day, estimated from the mean cell density in the growth zone (about 252 μg width) over a 3-month period. In order to compensate for loss of dopaminergic innervation induced by intravitreal 6-OHDA, the proliferation rate appeared to be facilitated significantly compared to that in normal retinas, and long and centrally extending processes were found to emerge from the DA cells formed earliest after intravitreal injection of 6-OHDA.     

Electrophysiological studies of d-lysergic acid diethylamide in the visual system

Experiments involving the use of LSD and observing its effects on neurons involved in the processing of visual information are reviewed. These studies typically involved either intravenous or iontophoretic application of the compound. Both modes of application appeared to block the optic afferent synapse at the level of the dorsal lateral geniculate nucleus and to alter the evoked activity of visual cortical neurons. Increasing the dose of LSD regardless of the manner in which it was applied tended to produce depression of both spontaneous and visually driven activity. The receptive field properties of the neurons at all levels of the visual system appear to remain intact after LSD despite changes in spontaneous activity. The effect of LSD on non-specific afferents to the dorsal lateral geniculate nucleus is depicted in relationship to two of the different kind of relay cells located in this structure. Data on LSD interaction with the effects of midbrain stimulation on “X” and “Y” neurons is presented.     

Response of dopaminergic neurons in cat to auditory stimuli presented across the sleep-waking cycle

The response of dopaminergic neurons of the substantia nigra pars compacta to auditory clicks continuously presented across the sleep-wake cycle was studied in cats. The initial excitatory followed by inhibitory response to the click which occurred during quiet waking diminished as the cat progressed into slow-wave sleep and was absent during REM sleep. Upon awakening from REM sleep, dopamine neurons once again displayed an excitatory/inhibitory response to the clicks, implying that the decrease across the sleep-wake cycle was not attributable to long-term habituation.     

Potentiation of apomorphine-induced stereotypies by naloxone and L-prolyl-L-leucyl-glycinamide

We compared the influences of pretreatment with the narcotic antagonist drug naloxone and the neuropeptide L-prolyl-L-leucyl-glycinamide (PLG) upon apomorphine-induced stereotypic climbing activity in mice and apomorphine-induced contralateral rotational behavior in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. Naloxone produced dose-related potentiation in the mouse climbing model, while PLG was without effect. On the other hand, PLG produced dose-related potentiation in the rat rotational paradigm, while naloxone was without appreciable influence. These findings show an asymmetrical potentiation of apomorphine by naloxone and PLG in these two standard experimental models of striatal dopaminergic activity.     

Inhibition by DN-1417 (a TRH derivative) of [3H]GABA binding in the rat brain

The administration of DN-1417, a synthetic derivative of TRH with more potent central action, significantly reduced specific [3H]GABA binding in the cerebellum, whereas [3H]GABA binding in the cerebral cortex was not changed. Scatchard analysis showed that the decreased [3H]GABA binding in the cerebellum was due to decreased binding sites of both high and low affinities. [3H]GABA binding to brain synaptic membranes was not affected by the addition of either TRH or DN-1417 in vitro. These findings suggest that TRH may play a role in regulating GABA receptors in the rat cerebellum.     

Control of substantia nigra pars reticulata neurons by the nucleus accumbens

In alpha-chloralose anesthetized, immobilized and ventilated cats stimulation of the nucleus accumbens (NA) evokes either inhibition or brief excitation followed by inhibition of extracellularly recorded spontaneously active or sural driven units in substantia nigra pars reticulata (SNpr). Inhibition peaked 50-80 msec following the onset of NA stimulation and persisted for about 300 msec. Pharmacologic interventions designed to characterize this inhibition were performed. Bicuculline, 0.01 to 0.1 mg/kg IV, consistently antagonized NA elicited suppression of SNpr cells. Diazepam 0.5 mg/kg effectively reversed bicuculline actions. Inhibition of spontaneously active units as well as sural excited units was blocked by bicuculline. Strychnine 0.1 to 0.5 mg/kg IV failed to affect inhibition arising from NA. These data suggest that, analogous to the GABAergic striatonigral pathway, inhibition of SNpr cells arising from NA utilizes GABA as a transmitter.