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S Saporta

Publications and source records attributed to S Saporta.

At least 55 records · Page 3Linked to original sources

How plastic is the central nervous system?

Ramon y Cajal expressed the fatalistic view in 1928, of the central nervous system's response to damage that "...once the development was ended, the fonts of growth and regeneration of the axons and dendrites dried up irrevocably. In adult centers, the nerve paths are something fixed, ended, immutable. Everything may die, nothing may regenerate." Recently, however, new techniques for studying the nervous system have led to a reversal of thought. It is now clear the central nervous system (CNS) is remarkably plastic. While neurons cannot be replaced once they are lost through traumatic damage, the action of neurotoxins or disease processes, remaining neurons are capable of a remarkable array of responses under the appropriate conditions. The lines of research that led to this new concept are briefly explored and also current directions being pursued to understand factors that control CNS plasticity.

Adult↗

Enhancement of horseradish peroxidase histochemistry and/or uptake with radiocontrast media.

The effects of dissolving horseradish peroxidase (HRP) or HRP conjugated to wheatgerm agglutinin (WGA-HRP) in radiocontrast media (MD76) on the intraaxonal transport and enzymatic activity of these tracers were evaluated both in vivo and in vitro. The in vivo studies showed that more reaction product was visible in the L4 dorsal horn following soaking of the sciatic or peroneal nerve, or following cutaneous injection of WGA-HRP, when WGA-HRP was dissolved in MD76, as compared to dissolving WGA-HRP in distilled water. Additionally, there appeared to be an enhancement of anterograde transport and a reduction of retrograde transport of WGA-HRP when this tracer was dissolved in MD76, as compared to dissolving it in distilled water. The in vitro studies indicated that radiocontrast media increased the enzymatic activity of both WGA-HRP and HRP as compared to their enzymatic activity in distilled water when assayed spectrophotometrically. Data are presented that indicate some binding (about 4%) of HRP with MD76. This binding of HRP with organically bound iodine may account for the enhancement of anterograde transport and/or increased enzymatic activity.

Animals↗

The release of pituitary LH and sprouting of LH-releasing hormone (LHRH)-containing neurons after anterior hypothalamic deafferentation.

The chronology of changes in plasma luteinizing hormone (LH) and the distribution of immunoreactive neuronal processes containing LH releasing hormone (LHRH-ir) were studied in the female rat after surgical interruption of anterior neural connections of the mediobasal hypothalamus (MBH). Spontaneous LH surges on the afternoon of proestrus and LH release after estradiol benzoate (EB) followed 48 h later by progesterone (P) administration were studied in ovariectomized (OVX) rats. The maximum increase in plasma concentrations (delta maxLH) after EBP was calculated for each rat at several intervals over 140 days. Control animals given EBP at monthly intervals after OVX had comparably large delta maxLH surges during the first few months of study. However, a gradual decline in control delta maxLH followed becoming significant 3 months after the start of the experiment. In contrast, frontal cuts (FC), which interrupted anterior MBH connections, produced an abrupt decrease in delta maxLH surges after EBP to 11% of preoperative levels. However, during subsequent EBP trials, there was a gradual improvement in LH surges to about 50% of preoperative levels over 100 days. In some cases, individual improvement became equal to preoperative LH surge levels, in others there was no recovery. Examination of LHRH-ir nerve fiber growth responses after FC suggested that sprouting by these peptide-containing neuronal processes may have contributed to the functional improvements observed.

Animals↗

Functional associations among simultaneously monitored lateral medullary respiratory neurons in the cat. I. Evidence for excitatory and inhibitory actions of inspiratory neurons.

Data were obtained from 45 anesthetized (Dial), paralyzed, artificially ventilated, bilaterally vagotomized cats. Arrays of extracellular electrodes were used to monitor simultaneously the activities of lateral medullary respiratory neurons located in the rostral and caudal regions of the ventral respiratory group. The average discharge rate as a function of time in the respiratory cycle was determined for each neuron and concurrent phrenic nerve activity. Most cells were tested for axonal projections to the spinal cord or the ipsilateral vagus nerve using antidromic stimulation techniques. Seven hundred and sixty-one pairs of ipsilateral respiratory neurons that contained at least one neuron whose maximum discharge rate occurred during the inspiratory phase were analyzed by cross-correlation of the simultaneously recorded spike trains. Twenty-three percent of the 410 pairs of inspiratory (I) neurons showed short time scale correlations indicative of functional association due to paucisynaptic connections or shared inputs. Eight per cent of the 351 pairs composed of an I cell and and expiratory (E) neuron were correlated. We found evidence for excitation of both bulbospinal I neurons and I cells that were not antidromically activated by stimulation of the spinal cord and vagus nerve (NAA neurons) by NAA I cells. We also obtained data suggesting inhibitory actions of cells whose maximum discharge rate occurred in the first half of the I phase (I-DEC neurons). These actions included inhibition of other I-DEC neurons, inhibition of cells whose greatest firing rate occurred in the last half of the I phase (I-AUG neurons), inhibition of E-DEC neurons, and inhibition of E-AUG cells. Sixty-two percent (31/50) of the correlations that could be interpreted as evidence for an excitatory or inhibitory paucisynaptic connection were detected in pairs composed of a caudal and a rostral ventral respiratory group neuron. Eighty-eight percent (14/16) of proposed intergroup excitatory connections involved a projection from the rostral neuron of the pair to the caudal cell, whereas 73% (11/15) of proposed inhibitory connections involved a caudal-to-rostral projection. These results support and suggest several hypotheses for mechanisms that may help to control the development of augmenting activity in and the timing of each phase of the respiratory cycle.

Animals↗

Loss of spinothalamic tract neurons following neonatal treatment of rats with the neurotoxin capsaicin.

The purpose of the present experiments was to determine whether the organization of spinothalamic tract (STT) cells of adult rats was altered following the loss of most of their small-diameter peripheral afferent fibers, resulting from the neonatal administration of capsaicin. Rat pups were randomly assigned to serve as normal controls, to serve as vehicle controls, or to receive subcutaneous injections of capsaicin (50 mg/kg) on postnatal day (PND) 1, 2, 7, or 15; or an injection on PND 1, 3, and 5. When 60 days old, they were anesthetized and received 0.1-microliter thalamic injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) in the area of the central lateral nucleus (CL), the posterior group (PO), and the ventrobasal complex (VB), or the area of CL or VB. Following a survival time of 48 hr, the animals were perfused, and neuronal HRP reaction product was visualized with tetramethylbenzidine. The number and distribution of WGA:HRP-labeled STT neurons varied in treated animals with the time of capsaicin injection. Rats injected with capsaicin on or before PND 7 demonstrated a significant reduction of labeled STT neurons from the superficial laminae of the spinal cord. Additionally, lamina I neurons were unlabeled in animals treated before PND 7 even with large thalamic injections. Differences in the distribution of labeled STT neurons could not be demonstrated for animals injected with capsaicin on PND 7 or PND 15, though there was a decrement in the number of labeled neurons in PND 7 animals. In order to make certain that absence of labeled STT neurons was not due to some technical error or to insufficient spread of WGA:HRP at the site of injection, six injections of WGA:HRP were placed in the thalamus of PND 1 and normal adult animals. Where the dense core of reaction product did not extend caudal to the posterior commissure, WGA:HRP-positive neurons were located and distributed similarly to those cases described for large thalamic injections. Neurons in superficial laminae of the nucleus proprius and lamina I of the contralateral spinal cord were labeled where the dense core of the thalamic injection extended into the mesencephalon of PND 1 animals. These studies indicate that the number and distribution of the cells of origin of the STT are altered in adult rats following their neonatal treatment with the neurotoxin capsaicin, and that this effect is limited to a critical postnatal period.

Age Factors↗

Electrochemical stimulation of plasma LH and hypothalamic norepinephrine concentrations at short- and long-term intervals after hypothalamic knife cuts.

Norepinephrine (NE) concentrations in several diencephalic locations were studied in female rats in conjunction with luteinizing hormone (LH) release after medial preoptic area (MPOA) stimulation at short (7 days) and longer time intervals after surgical interruption of anterior or anterolateral neural connections of mediobasal hypothalamus (MBH). Concentrations of diencephalic NE were altered in two general ways after brain surgery: (1) transient early postoperative increases in some regions which appeared unrelated to the type of surgery performed; and (2) other specific decreases in NE concentration which were related to the types of surgery performed and whether a particular ascending noradrenergic pathway was interrupted. At 180 days after surgery, these two types of change in NE concentrations were no longer present. Maximum increases in plasma LH concentrations observed after electrochemical stimulation of the MPOA at either 7 or 180 days after MBH deafferentation also varied according to: (1) the postoperative interval studied; and (2) the location of pathway interruption. Interruption of anterior MBH pathways showed only a transient (7 day interval) reduction in LH release after MPOA stimulation, whereas when both lateral and anterior pathways were severed, there was a more nearly permanent (180 day interval) disruption of LH release after stimulation. The results of these studies support the contention that anterolateral MBH neural connections may constitute a dynamic neural substrate contributing to a gradual improvement in neuroendocrine function observed after early surgical disconnections.

Animals↗

Long-term reorganization of afferents to the mediobasal hypothalamus following retrochiasmatic knife cuts. A study using horseradish peroxidase.

Retrochiasmatic knife cuts produce a series of dynamic changes across time in the luteinizing hormone-releasing hormone and catecholamine content of the mediobasal hypothalamus (MBH). We have examined the sources of afferents projecting to the mediobasal hypothalamus of female rats at 7, 60 and 90 days following retrochiasmatic frontal cut (FC) surgery using the intra-axonal retrograde transport of horseradish peroxidase (HRP) in order to better define the functional plasticity demonstrated by the MBH at these time periods after damage. Age-matched, previously unoperated, female rats served as controls. Small HRP injections placed in the ventromedial nucleus (VMN) in control animals labelled neurons within the VMN, dorsomedial nucleus (DMN) and lateral hypothalamic area (LHA). Larger injections also labelled neurons in the anterior hypothalamic area (AHA), preoptic area (POA), septal nuclei, periventricular nuclei (PVN), supraoptic nucleus (SON), zona incerta (ZI) and suprachiasmatic nucleus (Schn). Seven days after surgery, no labelled neurons could be detected rostral to the knife cut when the injection site was confined to the boundary of the glial scar. At 60 days, labelled soma were observed in LPOA, POA, AHA, PVN, SON and ZI. At 90 days only the SON contained labelled neurons rostral to the knife cut. These results suggest a dynamically changing pattern of innervation to the MBH following damage.

Afferent Pathways↗

Neural projections of the preoptic-suprachiasmatic region to the median eminence in the rat: a quantitative autoradiographic study.

The possibility of a preferential distribution of projections from the preoptic-suprachiasmatic region (POA-Sch) to the median eminence in the male rat was studied using autoradiographic and computer procedures. A cocktail of [3H]leucine-[3H]proline was injected into the POA-Sch. Animals were killed after either 1, 4, or 24 h of incorporation time (IT). The number of silver grains per 25-micron square was counted throughout the median eminence. Squares with silver grain densities at or above the 75 percentile of the population for any given IT group were labeled as "concentrating areas." The distribution of these concentrating areas in median eminence tissue was analyzed utilizing univariate procedures. Visual inspection of the distribution of silver grain densities in a rostrocaudal fashion indicated the likelihood of uneven distribution; however, these differences were not statistically significant. In the dorsoventral plane, results indicated that the highest silver grain density was at 50 to 75 micron from the floor of the 3rd ventricle. Such distribution was apparent both ipsi- and contralateral to the injection site, but was greater on the ipsilateral side.

Animals↗

Conjugated dimers of horseradish peroxidase as neuroanatomical tracers.

Horseradish peroxidase dimer (HRP-HRP) and monomer (HRP) were compared in their ability to act as neuroanatomical tracers. Dimers exhibited less diffusion at the site of injection. At 48-72 h survival periods, there were no appreciable differences in the retrograde neuronal labeling produced by these two compounds. However, at 7 days survival, there was little retrograde labeling due to the presence of monomer while dimer labeling was still intense.

Animals↗

Neural damage following retrochiasmatic knife cuts in the rat.

In order to define neuronal damage produced by sham, frontal and frontolateral hypothalamic knife cuts known to effect neuroendocrine and behavioral variables, we designed a retractable knife capable of delivering horseradish peroxidase as a cut was being produced. Damaged neurons filled with homogeneous reaction product were found in virtually all hypothalamic nuclei. A similar distribution of damage was produced by frontolateral (FLC), frontal (FC) or sham cuts--the primary differences being the greater density of damaged neurons in hypothalamic nuclei and labeling of the ventral tegmental area of Tsai in FLC and FC animals. The difference between FC and FLC animals was primarily one of degree of damage. The amount of damage produced by the sham surgery is consistent with the idea that sham surgeries produce endocrine dysfunctions intermediate between frontal cut animals and unoperated controls. It is interesting to note that a number of nuclei damaged by these surgeries provide aminergic innervation to the hypothalamus.

Animals↗

The organization of projections to selected points of somatosensory cortex from the cat ventrobasal complex.

The organization of neurons in the cat ventrobasal complex (VB) which project to somatosensory cortex (SI) was investigated by the use of the retrograde transport of the enzyme horseradish peroxidase (HRP). Two histochemical procedures were used to visualize retrogradely transported HRP. Injections of HRP in electrophysiologically characterized points of SI cortex labeled distinctive zones of neurons in VB ipsilateral to the injections. Injections placed in the forelimb or hindlimb cortical areas labeled laminar-like aggregates of neurons have long axis corresponded to the long axis of VB. Injections of the SI trigeminal representation resulted in very compact aggregates of HRP positive neurons which were less clearly laminar. The density of projection from VB to various portions of SI paralleled the general innervation density of the peripheral skin. Injections of the cortical vibrissal, face and forepaw representations labeled a greater number of neurons in VB per unit area of cortex injected than did injections of the hindpaw or trunk representations. For a given somatotopic area, the number of labeled neurons in VB increased linearly as the area of the cortical HRP injection increased. Differences in the sensitivity of each histochemical procedure and the relationship of differing sensitivities to the observed results are also discussed.

Animals↗