bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of temporary blockage of semicircular canals on the loss and recovery of vestibuloocular reflexes
Authors: Barmack NH
Published: March 2018

The efficacy of the technique of semicircular canal plugging in selectively blocking the function of individual semicircular canals was evaluated in rabbits. The horizontal and vertical vestibuloocular reflexes (HVOR, VVOR) and the horizontal optokinetic reflex (HOKR) were measured before the horizontal or anterior semicircular canals (HSCs, ASCs) were plugged bilaterally with small spindles of silver wire. These reflexes were also measured after the plugs were removed. The gain of the HVOR was reduced to less than 0.05 at all frequencies tested after plugs were inserted into the HSCs. The gain of the HOKR was not influenced by the plugging operation. These data were interpreted to mean that the plugs blocked the normal fluid dynamics of the HSCs, but did not alter the spontaneous activity of HSC afferents. The gain of the VVOR was not reduced by plugs of the HSCs. The gain of the VVOR was reduced by plugs of the ASCs. The residual VVOR was attributed to stimulation of the utricular otoliths at lower frequencies and stimulation of the posterior semicircular canals at higher frequencies. The gain of the HVOR was reduced 10–40% by plugs of the ASCs. These data, in conjunction with the presence of a small residual gain of the HVOR following bilateral plugs of the HSCs, suggest that the ASCs contribute to the HVOR. The gains of the HVOR and VVOR recovered to within 88% of the preplug values once the plugs of the HSCs or ASCs were removed. However, the protracted time course of this recovery, 10–15 d, indicated that the plugging operation, although reversible, does cause some temporary damage to the peripheral labyrinth.
The induction and compensation of asymmetric eye movements following unilateral blockage of a horizontal semicircular canal in the rabbit
Authors: Barmack NH , Pettorossi VE
Published: March 2018

The influence of unilateral plugs of the left horizontal semicircular canal (LHC plugs) of rabbits on the development and compensation of asymmetric eye movements evoked by horizontal vestibular stimulation was studied. LHC plugs caused an immediate reduction of 50–65% in the gain of the horizontal vestibuloocular reflex (HVOR). This reduction in gain was achieved without altering the symmetry of the HVOR, and was accompanied by a change in the axial alignment of eye movements evoked by vestibular stimulation about the vertical (HVOR) and longitudinal (VVOR) axes. Postoperative asymmetry of eye movements developed 12–48 hr after the plugging operation. The development of asymmetry was reduced if the rabbit was restrained for 24 hr, thereby minimizing vestibular stimulation following the plugging operation. Over a 3–4 week period, the normal symmetry of eye movements was restored and the axial alignments of the HVOR and VVOR returned to the preoperative values. The gain of the HVOR did not recover. The horizontal cervicoocular reflex (HCOR) was examined before the plugging operation and after compensation of asymmetry was complete. The gain and phase of the HCOR were not altered. A relatively simple set of explanations at a cellular level is proposed to account for the induction and compensation of asymmetric eye movements following a unilateral plug of the horizontal semicircular canal.
Rescue of lesioned septal cholinergic neurons by nerve growth factor: specificity and requirement for chronic treatment
Authors: Montero CN , Hefti F
Published: March 2018

We earlier reported that chronic intraventricular injections of NGF into adult rats with partial transection of the fimbria prevent the lesion-induced disappearance of cholinergic neurons in the medial septal nucleus and the diagonal band of Broca (Hefti, 1986). The present study assessed the specificity and treatment requirements of this effect of NGF. Immunohistochemical visualization of NGF receptors (NGF-R) revealed that these molecules are selectively located in forebrain cholinergic neurons of unlesioned brains. Fimbrial transection resulted in transient accumulation of NGF-R in proximal stumps of lesioned axons but failed to induce the expression of NGF-R by other cells in the septal area or near the lesion. Two to three weeks after lesioning, the number of septal neurons expressing NGF-R was reduced by approximately 50% in parallel with the reduction of the number of neurons expressing cholinergic marker enzymes. Repeated intraventricular NGF injections during 4 weeks prevented the disappearance of these cells. Fimbrial transections also reduced the number of septal GABAergic neurons visualized by glutamate decarboxylase immunohistochemistry. The loss of GABAergic neurons was not prevented by NGF. These findings suggest that NGF prevents the lesion-induced degeneration of cholinergic neurons by directly acting on NGF-R expressed by cholinergic cells and that NGF does not affect any neuron with an axonal lesion. Delayed start of the NGF treatment failed to prevent the disappearance of lesioned cholinergic neurons, providing evidence that NGF treatment indeed promotes the survival of these cells rather than simply upregulating the expression of transmitter-specific enzymes. A single injection of NGF at the time of the lesion was not sufficient to prevent the lesion-induced degeneration of cholinergic neurons. Furthermore, termination of chronic NGF treatment after 4 weeks was followed by loss of septal cholinergic neurons after an additional 4 weeks. These findings suggest that the continuous presence of NGF during more than 4 weeks is required to prevent the degeneration of cholinergic cells. The data are discussed in the context of a possible physiological role of NGF in the function of adult forebrain cholinergic neurons.
The neuropeptide egg-laying hormone modulates multiple ionic currents in single target neurons of the abdominal ganglion of Aplysia
Authors: Jansen RF , Mayeri E
Published: March 2018

The bag cell neurons of the abdominal ganglion of Aplysia are a useful system for the study of peptidergic neurotransmission. A 20 min burst of impulse activity in the bag cells induces or augments repetitive firing in LB and LC neurons in the abdominal ganglion for up to several hours. Previous experiments have indicated that this effect is mediated by the putative bag cell transmitter egg-laying hormone (ELH). Using voltage-clamp analysis we found that bag cell bursts (BCBs) evoke long- lasting changes in membrane current in these neurons that are mimicked by the application of ELH. The combined ELH-evoked current is inward at all membrane potentials between -110 and -10 mV and consists of 3 separable currents persisting for 30–120 min. They include (1) a depolarizing current that is activated at membrane potentials above -40 mV. This current, termed ISI, is blocked by prolonged exposure to 10 mM Ni2+/0 mM Ca2+ and is not abolished by 0 mM Na+ or 100 mM TEA+/0 mM Na+ in the bathing medium. It is therefore a Ca2+-sensitive current and does not involve Na+ as a charge carrier. (2) There is a hyperpolarizing current that is activated at membrane potentials below approximately -70 mV. This current, termed IR, is blocked by external Rb+ (5 mM) and Cs+ (10 mM) and has a chord-conductance that shifts with the external [K+] according to the Nernst potential for potassium. It is therefore an inwardly rectifying K+ current. (3) There is a small, steady depolarizing current, termed Ix. This current is the only one that remains after prolonged exposure to 10 mM Ni2+/0 mM Ca2+- containing bathing medium. It is Na+ dependent and is associated with a small increase in membrane conductance that is largely independent of membrane voltage. All 3 currents are slow to inactivate; they appear to sum algebraically to produce the net BCB- or ELH-evoked current.
Cholinergic regulation of protein III phosphorylation in bovine adrenal chromaffin cells
Authors: Haycock JW , Greengard P , Browning MD
Published: March 2018

Protein IIIa (Mr approximately 74,000) and protein IIIb (Mr approximately 55,000), referred to collectively as protein III, are synaptic vesicle-associated phosphoproteins found in all regions of the rat nervous system and in the rat adrenal medulla. In the present study, the presence of protein III and the regulation of its phosphorylation were examined in chromaffin cells isolated from bovine adrenal medullae. Protein III was present in chromaffin cells isolated and purified from bovine adrenal medullae. The levels of protein III were moderately enriched in purified chromaffin cells compared with whole adrenal medullae. Preincubation of chromaffin cells with 32PO4 led to the endogenous phosphorylation of protein III, and phosphopeptide maps of chromaffin cell protein III were similar to those of protein III from bovine cerebral cortex. Treatment of the chromaffin cells with ACh produced calcium-dependent increases in both the phosphorylation of protein III and the release of 3H- norepinephrine. These effects of ACh were mimicked by nicotine but not by muscarine. Other secretagogues (elevated K+, veratridine, Ba2+) also increased both the phosphorylation of protein III and the release of 3H- norepinephrine. However, detailed characterization of the secretagogue- induced increases in protein III phosphorylation and 3H-norepinephrine secretion suggested that protein III phosphorylation was more directly associated with an increase in intracellular calcium than with secretion per se.
Functional role of corticoperipheral loop circuits during voluntary movements in the monkey: a preferential bias theory
Authors: Favorov O , Sakamoto T , Asanuma H
Published: March 2018

The functional role of the sensory input to the motor cortex in the execution of voluntary movements is still controversial. We have proposed that the input functions by changing the excitability of cortical efferent columns before and during movements (Asanuma and Arissian, 1984). Experiments were performed to support this hypothesis. Monkeys were trained to sit still in a chair and to pick up a food pellet from a food board rotating at a high speed, so that the subjects had to concentrate their efforts to pick up the pellet. Microelectrode recordings were made from pre- and post-central cortical neurons related to hand movement during the pickup task. It was found that neurons in the motor (10%) and in the sensory (5%) cortices started discharging far ahead of actual movement of the hand. EMGs in the target muscles, which were identified by microstimulation at the recording sites, revealed that some muscles changed their tone during these premovement discharges, although there were no visible movements of the hand. Section of the dorsal columns abolished the premovement discharges and also produced retardation of motor skills. The results supported the hypothesis that circulation of impulses between the cortical efferent columns and the periphery before the movement plays an important role in the execution of skilled movements.
An immunohistochemical study of the nerve growth factor receptor in developing rats
Authors: Yan Q , Johnson EM
Published: March 2018

Nerve growth factor (NGF) receptor expression was studied in rats between embryonic day 11 (E11) to postnatal day 10 (PND10) by using a monoclonal antibody, 192-IgG, that specifically recognizes rat NGF receptor. Sympathetic ganglia were lightly stained by 192-IgG for NGF receptor immunoreactivity (NGFRI) (E11-PND10). Neural crest-derived sensory ganglia were moderately to densely stained (E11-PND10). Areas in CNS innervated by the central processes of these ganglia were also stained. Parasympathetic ciliary ganglion showed some detectable staining (E16-PND6). Placode-derived sensory ganglia were stained more densely than that of neural crest-derived sensory ganglia. The most densely stained tissue for NGFRI was found in all peripheral nerves. Basal forebrain cholinergic neurons were NGFRI positive from E15 throughout the period examined. Motoneurons in both spinal cord and brain stem were positive for NGFRI between E15 and PND10. NGFRI staining was seen in a variety of sensory pathways and related structures, such as olfactory tract and glomerular layer of olfactory bulb; retina, optic nerve and tract, lateral geniculate nucleus, medial terminal nucleus of the accessory optic tract, and olivary pretectal nucleus; ventral cochlear nucleus and to a lesser degree in dorsal cochlear nucleus, superior olive, and nucleus of lateral lemniscus; solitary tract; cuneate nucleus, gracile nucleus, and ventroposterior thalamic nucleus. The specific staining was also found in some other CNS structures, including brain-stem reticular formation; amygdala; medial nucleus of inferior olive but not the rest of inferior olive, external granule cell layer and Purkinje's cells of cerebellum, and deep cerebellar nuclei. Some non-neuronal tissues such as meninges and dental tissue showed very distinctive staining. Limb buds and somites were NGFRI positive starting at E11, and the staining on muscle tissue became very dense at E15-E18 and largely disappeared around PND10. Embryonic thymus was positive for NGFRI. The adventitia surrounding blood vessels was very densely stained. The changes in NGFRI staining seen in this study suggest that NGF may have broader effects during development than previously thought.
Selective expression of high-affinity nerve growth factor receptors on tyrosine hydroxylase-containing neuron-like cells in neural crest cultures
Authors: Bernd P
Published: March 2018

A subpopulation of cultured neural crest cells undergoing differentiation have receptors for nerve growth factor (NGF) that exhibit a binding constant similar to that of the low-affinity NGF binding site (3.2 nM). Recent studies have shown that NGF receptors are not present on neuron-like cells immunoreactive for tyrosine hydroxylase (TH), serotonin, or vasoactive intestinal polypeptide. Since tissues innervated by sympathetic neurons in vivo produce NGF, we sought to determine whether NGF deficits in the tissue culture microenvironment may be one parameter preventing the expression of NGF receptors on TH-containing neuron-like cells. Neural crest cultures were therefore grown in complete tissue culture medium (15% fetal bovine serum and 5% chicken embryo extract), with or without exogenous NGF (50 ng/ml). Examination of light-microscopic radioautographs following incubation with 125I-NGF revealed that, if the cultures were supplemented with NGF for 7 d, approximately 33% of neuron-like cells exhibiting TH-like immunoreactivity possessed NGF receptors. There were no obvious morphological differences between TH-containing cells that did or did not have NGF receptors. Scatchard analysis of cultures grown under these conditions again demonstrated the sole presence of the low- affinity form of the NGF receptor (Kd, 3.4 nM). Embryonic catecholaminergic sympathetic neurons exhibit both high- and low- affinity forms of the NGF receptor, raising the possibility that the Scatchard analysis may not have been sensitive enough to detect the high-affinity form of the receptor on a relatively small population of cells. Therefore we used a morphological approach that took advantage of the different dissociation rates of the 2 receptor types.(ABSTRACT TRUNCATED AT 250 WORDS)
Control of sensory activation of granule cells in the fascia dentata by extrinsic afferents: septal and entorhinal inputs
Authors: Foster TC , Hampson RE , West MO , Deadwyler SA
Published: March 2018

Three groups of rats were trained to perform a differential discrimination task in a 2-tone operant conditioning paradigm. One group received electrolytic lesions of the medial septal nuclei, another received electrolytic or knife cut lesions of the entorhinal cortex. These groups were compared with a normal control group. Recordings of granule cells in the fascia dentata were obtained in all animals during criterion performance of the behavioral task. Both lesions produced disruption of behavioral discrimination in the form of increased error and intertrial responding. Granule cell discharges to the tone stimuli were disrupted by each type of lesion. Septal lesions reduced the differential discharge tendency to CS+ and CS- and changed granule cell firing on all trials to statistically resemble firing on CS- trials in normal animals. Extensive lesions in the entorhinal cortex or knife cuts that severed the perforant path caused near elimination of the tone-evoked discharges to both the CS+ and CS-tones. Septal and entorhinal lesions caused marked changes in the sequential dependence of the granule cell discharge compared with intact animals. Results are discussed in terms of the control of the granule cell discharge by the remaining afferent pathways in each type of lesion condition.
Evidence for two functionally distinct subpopulations of neurons within the rat striatum
Authors: Nisenbaum ES , Orr WB , Berger TW
Published: March 2018

Type I and Type II extracellular action potential waveforms were recorded from the rat striatum and studied with respect to their dependence on recording conditions, response to paired impulse stimulation of the corticostriatal pathway, and iontophoretic application of dopamine (DA). Results showed that the distinguishing characteristics of Type I and Type II waveforms are relatively independent of the degree of filtering, distance of the electrode tip from the target neuron, type of recording electrode, and firing rate of the neuron. Very low impedance electrodes, however, were found to mask the difference in spike shape. Electrical stimulation of cortical afferents results in excitation of both action potential waveforms, though the Type II class exhibits a significantly shorter latency than the Type I class. Paired impulse analyses revealed that both waveforms exhibit variation in the probability of discharge (facilitation or inhibition) to the second impulse of each impulse pair that are a function of the interimpulse interval. Most importantly, however, the probabilities of discharge of Type I and Type II neurons to the second impulse are inversely related, i.e., when one cell type exhibits facilitation, the other displays inhibition. These data demonstrate that Type I and Type II waveforms represent the activity of functionally different subpopulations of striatal neurons. Moreover, Type II neurons are found much more often than Type I cells, suggesting that the 2 cell classes may be represented with different frequencies within striatum. Finally, Type II neurons display at least a 5 times greater sensitivity to iontophoretically applied DA than Type I cells, suggesting that the 2 cell populations also are affected differentially by dopaminergic input from the substantia nigra.
Androgenic regulation of gap junctions between motoneurons in the rat spinal cord
Authors: Matsumoto A , Arnold AP , Zampighi GA , Micevych PE
Published: March 2018

Gap junctional plaques were found between androgen-sensitive motoneurons of the spinal nucleus of the bulbocavernosus (SNB), using thin-section and freeze-fracture techniques. The somata and proximal dendrites of SNB motoneurons were studied after retrograde labeling with cholera toxin conjugated to HRP. Of the gap junctions observed, 45% were somatodendritic, 35% were dendrodendritic, and 20% were somatosomatic. The removal of testosterone by castration dramatically reduced the number and diameter of the junctional plaques, and these changes were prevented by testosterone treatment. The results are the first demonstration of hormonal regulation of morphologically identified gap junctions in the CNS. The occurrence and hormonal dependence of gap junctional plaques between motoneurons of the lumbar spinal cord indicate that androgens regulate the degree of coupling between these cells, which may allow for the synchronization and amplification of the electrical activity in the nucleus.
Isolation, characterization, and evolutionary aspects of a cDNA clone encoding multiple neuropeptides involved in the stereotyped egg-laying behavior of the freshwater snail Lymnaea stagnalis
Authors: Vreugdenhil E , Jackson JF , Bouwmeester T , Smit AB , Van Minnen J , Van Heerikhuizen H , Klootwijk J , Joosse J
Published: March 2018

The cerebral neurosecretory caudodorsal cells (CDCs) of the freshwater pulmonate snail Lymnaea stagnalis control egg laying, an event that involves a pattern of stereotyped behaviors. The CDCs synthesize and release multiple peptides, among which is the ovulation hormone (CDCH). It is thought that each peptide controls a specific aspect of the processes involved in egg laying. We isolated and characterized a CDC- specific cDNA clone that encodes the ovulation hormone (CDCH). RNA blot analysis and in situ hybridization experiments demonstrated that the CDCs are the major cell groups in the cerebral ganglia that transcribe the CDCH gene. In addition to CDCH, the 259-amino acid-long CDCH preprohormone contains 11 other predicted peptides. The overall homology of the CDCH preprohormone with the egg-laying hormone (ELH) preprohormones of the marine opisthobranch snails Aplysia californica and A. parvula is very low (29 and 26%, respectively). However, a more detailed comparison revealed a highly differential pattern of conservation of peptide regions. Significant homology was found between the regions containing (1) CDCH and ELH, (2) repeated pentapeptides, (3) alpha-caudodorsal cell peptide and alpha-bag cell peptide, and (4) 2 regions representing as yet unidentified peptides. Insignificant homology was found when comparing regions containing the other predicted peptides. The conserved peptides probably control similar aspects of the egg-laying fixed action patterns in these distantly related gastropod species. The pentapeptide region exhibits the highest level of homology (75%); in addition, an extra pentapeptide has been generated on the CDCH precursor. This indicates a vital function of these peptides in Aplysia, as well as in Lymnaea species.
Evidence for the transneuronal regulation of cerebellin biosynthesis in developing Purkinje cells
Authors: Slemmon JR , Goldowitz D , Blacher R , Morgan JI
Published: March 2018

We have investigated the expression of a unique class of neuropeptides, the cerebellins, in normal and neurodevelopmentally mutant mice. Employing HPLC separation, gas-phase Edman sequencing, and immunocytochemistry, the normal Balb/c mouse cerebellum is shown to contain 2 Purkinje cell-specific neuropeptides, cerebellin and des-Ser1- cerebellin. In this strain of mouse the cerebellins appear during early postnatal development and their subsequent levels parallel the most dramatic period of cerebellar development: granule cell migration and parallel fiber formation, synaptogenesis, Purkinje cell dendritic maturation, and establishment of adult cytoarchitecture. In mutant mice (reeler, weaver, and staggerer), in which these early developmental events are markedly disrupted, Purkinje cells contain much lower levels of cerebellin and des-Ser1-cerebellin. In general there is a correlation between the formation and number of parallel fiber-Purkinje cell synapses and cerebellin levels. For example, the staggerer mutant, which totally lacks these synapses, is essentially devoid of cerebellin, whereas in reeler, cerebellin seems to be dependent upon the position of individual Purkinje cells and their ability to form contacts with granule cells. These results indicate that granule cells can modulate the level of cerebellin in Purkinje cells. A number of models to explain these data are discussed.
Expression of two developmentally regulated brain-specific proteins is correlated with late outgrowth of the pyramidal tract
Authors: Kalil K , Perdew M
Published: March 2018

The regulation of axon outgrowth is not well understood. In previous studies, however, axon elongation has been well correlated with expression of a small number of growth-associated proteins (GAPs). To identify other proteins whose expression could be correlated with axon outgrowth during development of CNS pathways, monoclonal antibodies were raised against growth cone particles isolated from neonatal hamster brains. Two of these antibodies recognized a brain-specific 33 kDa protein associated with intracellular membranes of axons and growth cones. Immunoblotting demonstrated a sharp developmental decline in levels of the protein in hamster brain during the first postnatal week and a more gradual decline thereafter. Immunocytochemical studies with the antibodies revealed ubiquitous staining of the neuropil during the first several days, which by the end of the first week became restricted to a few later-maturing pathways. Staining was most intense in the pyramidal tract and was well correlated with axon outgrowth, which continues until 14 d in this pathway. These results suggest that the 33 kDa protein may, like previously identified GAPs, play a role in axon elongation. Late outgrowth of the hamster pyramidal tract is also correlated with expression of another developmentally regulated protein, the high-molecular-weight neurofilament subunit (NF-H). Immunostaining with a monoclonal antibody that recognized phosphorylated NF-H demonstrated that this subunit does not begin to appear in the late-maturing pyramidal tract fibers until several weeks after birth, in striking contrast to intense immunoreactivity of other spinal cord pathways from postnatal day 1. This finding suggests that specific pathways may have a highly idiosyncratic time course for expression of neurofilament subunits.
A developmentally regulated chicken neuronal protein associated with the cortical cytoskeleton
Authors: Allsopp TE , Moss DJ
Published: March 2018

Monoclonal antibody 3D5 recognizes a single component of the neuronal membrane skeleton isolated from the chicken embryo brain. The 3D5 antigen is highly enriched in the CNS, and smaller amounts are found in the PNS. It is also present in non-neural tissues, but this is due to peripheral innervation. The biochemical and molecular properties of the 3D5 antigen are very similar to those of the previously described mammalian protein B-50 (Zwiers et al., 1985)/GAP 43 (Jacobson et al., 1986)/pp46 (Ellis et al., 1985)/F1 (Chan et al., 1986), and include anomalous SDS gel migration, acidic isoelectric point, and extraction from the cytoplasmic side of the plasma membrane only under extremely alkaline conditions. The 3D5 antigen is also developmentally regulated, with maximum expression in brain occurring at E14-E16, after which levels decrease approximately 4-fold in the adult. Immunofluorescence staining of cultured neurons shows that the 3D5 antigen is located in all parts of the cell but is particularly enriched in the growth cone and the growth cone filopodia. As the 3D5 antigen is enriched in the membrane skeleton, we suggest that this protein is involved in an association between the actin-containing cytoskeleton and the plasma membrane.
Physiological and anatomical consequences of infraorbital nerve transection in the trigeminal ganglion and trigeminal spinal tract of the adult rat
Authors: Renehan WE , Klein BG , Chiaia NL , Jacquin MF , Rhoades RW
Published: March 2018

Single-unit recording and retrograde tracing techniques were used to assess the receptive field properties, topography, and projections of rat trigeminal primary afferent neurons subsequent to transection of the infraorbital (IO) nerve in adulthood. Four hundred and fifty-eight units were recorded in the trigeminal ganglion ipsilateral to nerve section. Of these, 66.6% had IO receptive fields. Thirty percent responded to innocuous stimulation of vibrissae, 39.1% to guard hair deflection, 8.2% to gentle indentation or stretch of the skin, and 22.3% to noxious stimuli (compared to 77.2% vibrissa, 12.0% guard hair, 4.5% skin, and 6.3% noxious in normal animals). An additional 15 units were driven by a stimulating electrode placed on the IO nerve proximal to the site of the lesion but had no receptive field. Of the cells with vibrissa receptive fields, 33.3% were slowly adapting type I (SAI), 6.6% were slowly adapting type II (SAII), 32.2% were low velocity rapidly adapting (RA-LV), 20.0% were high velocity rapidly adapting (RA- HV), and 7.7% were nociceptive (NX, in normal animals 43.8% were SAI, 10.3% SAII, 27.6% RA-LV, 16.8% RA-HV, and 1.5% NX). A number of cells had receptive field properties not seen in normal animals. The single- unit recordings indicated that the topography of mandibular and ophthalmic representations in the ganglion were essentially normal, while the organization of the maxillary region of the ganglion was slightly abnormal. The ganglion physiology experiments were augmented by records from primary afferents in the trigeminal spinal tract (TrV). Eighty-one (72.2%) of the 112 fibers recorded in the TrV of normal rats had IO receptive fields. Of these, 73.2% responded to innocuous vibrissal stimulation, 14.6% to guard hair deflection, 8.5% to gentle indentation of the skin, and 2.5% to noxious stimuli. Of the 61 vibrissa units, 37.8% were SAI, 19.7% SAII, 37.8% RA-LV, 3.3% RA-HV, and 1.6% NX. In adult-lesioned animals, 81 (61.3%) of the recorded fibers had IO receptive fields. Of this number, 38.2% responded to vibrissae, 29.6% to guard hairs, 16.0% to skin, and 19.7% to noxious simuli. Of the vibrissa-sensitive units, 16.1% were SAI, 3.2% were SAII, 45.2% were RA-LV, 35.5% were RA-HV, and 3.2% NX. As in the ganglion recording studies, a number of abnormal receptive fields were documented.(ABSTRACT TRUNCATED AT 400 WORDS)
Nicotinic acetylcholine receptor-like molecules in the retina, retinotectal pathway, and optic tectum of the frog
Authors: Sargent PB , Pike SH , Nadel DB , Lindstrom JM
Published: March 2018

Forty-two monoclonal antibodies (mAbs) generated against nicotinic acetylcholine receptors (AChRs) from electric organ were tested for their ability to cross-react in the optic tectum of the frog Rana pipiens. Twenty-eight of the mAbs tested (67%) bound to the optic neuropil of the tectum as revealed by immunoperoxidase cytochemistry. The pattern of peroxidase stain for cross-reacting mAbs corresponded in position to a subset of the retinotectal projections. Electron microscopic examination revealed that peroxidase reaction product was associated with the surface of vesicle-containing profiles but not with synaptic sites. Removal of one retina resulted in the loss of immunoreactivity in the contralateral tectum. AChR-like immunoreactivity was also associated with the optic tract and optic nerve and with retinal ganglion cells. These results indicate that some classes of retinal ganglion cells bear AChR-like molecules on their surface. The existence of these molecules on ganglion cell axons and terminals seems the most likely explanation for the AChR-like immunoreactivity present in the tectum.
Stereotypic morphology of glutamatergic synapses on identified muscle cells of Drosophila larvae
Authors: Johansen J , Halpern ME , Johansen KM , Keshishian H
Published: March 2018

The distribution and morphology of glutamatergic synapses on Drosophila bodywall muscle fibers were examined at the single-synapse level using immunocytochemistry and electrophysiology. We find that glutamate- immunoreactive motor endings innervate the entire larval bodywall musculature, with each muscle fiber receiving at least one glutamatergic ending. The innervation is initiated at stereotyped locations on each muscle fiber from where moderately branched varicose nerve processes project over the internally facing muscle surface. Individual muscle fibers have distinct stereotypic patterns of nerve endings that occupy characteristic regions on the cell surface. The muscle-specific branching pattern of motor endings is reiterated by segmentally homologous fibers. Two morphological types of innervating nerve processes can be distinguished by their bouton size distributions: (1) Type I processes, which have localized branching and a broad size distribution of relatively large varicosities ranging up to 8 microns (mean diameter, 3.1 +/- 1.6 microns; +/- SD, n = 521), and (2) thinner Type II processes, which have a narrower distribution of small varicosities with a mean diameter of only 1.4 +/- 0.6 microns (+/- SD, n = 214). Immunoelectron microscopy with peroxidase-labeled second antibody demonstrates that the varicosities are surrounded by a subsynaptic reticulum, that they contain immunoreactive vesicles of about 30–50 nm, and thus probably represent synaptic release sites. By iontophoretic application of glutamate we mapped the responsive sites on the muscle surface and found an excellent correspondence between transmitter sensitivity and the patterns of endings as described by immunocytochemistry. In contrast to our finding of numerous glutamate iontophoresis-sensitive sites, we did not detect any aspartate- responsive muscles. These data provide strong new evidence for glutamate being an endogenous transmitter at the Drosophila larval neuromuscular junction.
Dynamic changes of excitatory amino acid receptors in the rat hippocampus following transient cerebral ischemia
Authors: Westerberg E , Monaghan DT , Kalimo H , Cotman CW , Wieloch TW
Published: March 2018

The changes in excitatory amino acid receptor ligand binding induced by transient cerebral ischemia were studied in the rat hippocampal subfields. Ten minutes of ischemia was induced by common carotid artery occlusion combined with hypotension, and the animals were allowed variable periods of recovery ranging from 1 day to 4 weeks. The binding of 3H-AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) to quisqualate receptors, 3H-kainic acid (KA) to kainate receptors, and 3H-glutamate to N-methyl-D-aspartate (NMDA) receptors as determined by quantitative autoradiography. One week following ischemia the CA1 region of the hippocampus displayed a severe (90%) dendrosomatic lesion with preservation of presynaptic terminals. This was associated with a 60% decrease in AMPA binding and a 25% decrease in glutamate binding to NMDA receptors. At 4 weeks postischemia, both AMPA and NMDA sites were greatly reduced. Although the dentate gyrus granule cells are resistant to an ischemic insult of this magnitude, this region showed marked changes in receptor binding. One week following ischemia, the AMPA and NMDA binding decreased by approximately 40 and 20%, respectively. Following 2 weeks of recovery, the NMDA binding was not significantly different from control level, while the AMPA binding remained depressed up to 4 weeks postischemia. The high density of KA binding sites in the inner molecular layer of the dentate gyrus was unaffected by the ischemic insult, despite an extensive degeneration of cells in the hilus of dentate gyrus which projects glutamatergic afferents to this area.(ABSTRACT TRUNCATED AT 250 WORDS)
Cholinergic regulation of arterial pressure by the C1 area of the rostral ventrolateral medulla
Authors: Giuliano R , Ruggiero DA , Morrison S , Ernsberger P , Reis DJ
Published: March 2018

In anesthetized, paralyzed rats intravenous administration of the acetylcholinesterase inhibitor physostigmine (PHY) (100 micrograms/kg) evoked a dose-related rise in arterial pressure (AP) and heart rate (HR) and an associated increase in sympathetic nerve activity (SNA). The responses to PHY were blocked by electrolytic lesions of, or microinjection of kainic acid into, a specific site in the rostral ventrolateral medulla containing a cluster of neurons immunoreactive for the adrenaline-synthesizing enzyme phenylethanolamine N- methyltransferase and corresponding to the C1 area of the nucleus reticularis rostroventrolateralis (RVL). The C1 area and its surround contain a heretofore unrecognized network of varicose neuronal processes and perikarya labeled immunocytochemically with a monoclonal antibody to the ACh-synthesizing enzyme, choline acetyltransferase (CAT). PHY increased, by over 3-fold, the spontaneous activity of reticulospinal cardiovascular neurons in the C1 area which excite preganglionic sympathetic neurons in the intermediolateral spinal column. The effects of PHY on AP, SNA, and the discharge of reticulospinal neurons were blocked by systemic administration of the muscarinic antagonist scopolamine. Microinjections within the C1 area of the RVL of scopolamine, the M2-selective muscarinic receptor antagonist AF-DX 116, or the high-affinity choline uptake inhibitor hemicholinium-3 blocked the pressor effects of PHY. The nicotinic antagonist hexamethonium and the M1-selective muscarinic receptor antagonist pirenzepine were without effect. We conclude that (1) the increases in AP, HR, and SNA elicited by the systemic administration of PHY result from the augmented action of ACh released from cholinergic terminals within the C1 area of the RVL; (2) the locally released ACh acts through muscarinic receptors of the M2 subtype within the C1 area to produce excitation of intrinsic reticulospinal sympathoexcitatory neurons, thereby increasing the activity of sympathetic preganglionic neurons and consequently elevating AP and HR; and (3) while the specific function of the cholinergic innervation of the C1 area in cardiovascular regulation is unknown, it may contribute to the tonic regulation of AP.
Cortical areas involved in horizontal OKN in cats: metabolic activity
Authors: Herdman SJ , Tusa RJ , Smith CB
Published: March 2018

Cerebral cortex improves optokinetic responses to high target velocities, but the specific cortical areas involved are unknown. Using the 14C-deoxyglucose technique, we compared local rates of cerebral glucose utilization in cats viewing a moving optokinetic nystagmus (OKN) drum (experimental group) with those in cats viewing a stationary OKN drum (control group). In the experimental group, glucose utilization was increased in areas 17 and 18 and in 4 areas in suprasylvian cortex (21a, 21b, PMLS, and VLS). There were no changes in glucose utilization in areas 7, 19, 20a, 20b, ALLS, AMLS, DLS, PLLS, the posterior suprasylvian area, and the splenial visual area. The increases in glucose utilization in areas 17 and 18 were most significant in the granular layers (inner III and IV). In areas 21a, 21b, PMLS, and VLS, the increases in glucose utilization extended from layers II through V. There was also a regional distribution of the increase in glucose utilization within each of these areas in the experimental animals. The increase in glucose utilization did not include the rostral portion of PMLS or the borders between areas PMLS and 21a, and VLS and 21b. In addition, there was a smaller increase in glucose utilization at the borders between areas 17 and 18 than in other portions of these 2 areas. The results indicate that areas 17, 18, 21a, 21b, PMLS, and VLS may be involved in the cortical modulation of horizontal OKN. The laminar distribution of label within the cortical areas corresponds with the distribution of projections from the dorsal lateral geniculate nucleus to areas 17 and 18, and from areas 17 and 18 to PMLS. The regional distribution of the metabolic activity within areas 17, 18, and PMLS coincides with that portion of cortex expected to be excited by either the spatial frequency of the stimulus or the retinalslip velocity (drum velocity minus slow phase eye velocity) occurring during the eye movements.
Developmental expression of reactivity to monoclonal antibodies generated against olfactory epithelia
Authors: Carr VM , Farbman AI , Lidow MS , Colletti LM , Hempstead JL , Morgan JI
Published: March 2018

The developmental expression of immunocytochemical reactivity to 3 monoclonal antibodies (Mabs Neu 4, Neu 5, and Neu 9) that were generated against adult rat olfactory epithelium was examined in olfactory tissues of embryonic rats. Tissues examined included the nasal olfactory epithelium, nerve, and olfactory bulb, as well as vomeronasal epithelium and nerve. Reactivity patterns of these Mabs in adult rats have been described previously (Hempstead and Morgan, 1985a). All 3 Mabs show reactivity on the cell surfaces of neurons, axons, and dendrites of the olfactory epithelium proper. Neu 5 alone shows reactivity on the dendritic knobs, site of transduction of the olfactory stimuli. These reactivities appear early, suggesting developmentally significant roles for the antigens to these Mabs. For Neu 5 and Neu 9 initial reactivity occurs on outgrowing olfactory axons at E13. Dendritic and perikaryal reactivities begin appearing at E14. For Neu 4 initial reactivity occurs simultaneously on olfactory neuronal perikarya, axons, and dendrites at E14. Reactivity also occurs on cells that migrate from the olfactory epithelium and are associated with the olfactory nerves. Within the developing olfactory bulb, Neu 5 behaves as a general cell-surface marker. Neu 4 and Neu 9, however, show enhanced reactivity in the glomerular layer after the onset of synaptogenesis. Reactivity is also seen in the nasal respiratory epithelium and in the vomeronasal epithelia and nerve. Neu 5 and several antibodies to rat neural cell adhesion molecules (N-CAMs) show similar, although not identical, immunohistochemical staining patterns. They also react with the same bands in Western blots of brain membrane preparations. Western blots of Neu 5-reactive material also show developmental and spatial correlations of apparent molecular-weight distributions expected of N-CAM-like components as well.
Visual cortex development in the ferret. I. Genesis and migration of visual cortical neurons
Authors: Jackson CA , Peduzzi JD , Hickey TL
Published: March 2018

The production of ferret visual cortical neurons was studied using 3H- thymidine autoradiography. The genesis of cortical neurons begins on or slightly before embryonic day 20 (E20) of the 41 d gestational period, continues postnatally until 2 weeks after birth (P14), and follows an inside-out radial gradient with neurons for the deeper cortical layers being generated before those for the superficial layers. Layer I neurons are generated both early (E20-E30) and late (P1-P14) in the period of cortical neurogenesis and, thus, provide at least a partial exception to the inside-out gradient of cortical neurogenesis. Tangential gradients of cortical neurogenesis extend across areas 17 and 18 in both the anterior-to-posterior and lateral-to-medial directions. Neither of these gradients bears a meaningful relationship to the cortical representation of the visual field. Most infragranular and granular layer neurons are generated prenatally, while most supragranular layer neurons are produced postnatally. Neurons destined for a given layer are produced over a period of several days, and the neurons generated on any given day contribute to the formation of 2 or more cortical layers. In general, prenatally generated neurons complete their migration in 1 week or less, while most postnatally generated neurons require approximately 2 weeks to complete their migration.
A morphometric analysis of functionally defined subpopulations of neurons in the paraventricular nucleus of the rat with observations on the effects of colchicine
Authors: Rho JH , Swanson LW
Published: March 2018

Two populations of neurons in the paraventricular nucleus of the hypothalamus that have different efferent projections and physiological roles in the regulation of visceral responses were characterized morphologically with a combined intracellular filling, retrograde tracer, and immunohistochemical method. Neuroendocrine cells were retrogradely labeled by an intravenous injection of Fast blue, and distinguished from descending neurons that were retrogradely labeled by an injection of fluorogold into the spinal cord. Retrogradely labeled neurons were selectively penetrated and filled intracellularly with Lucifer yellow to visualize detailed features of their morphology. Corticotropin-releasing hormone (CRH)-containing neurons were distinguished from other neuroendocrine cells by immunostaining the tissue with an antiserum to rat CRH. Morphometric features of defined populations of neurons were then quantified and reconstructed graphically to generate multicellular montage drawings that demonstrate their spatial organization. Descending neurons were further separated into dorsal and ventral medial parvicellular components, while the neuroendocrine population was differentiated into parvicellular and magnocellular groups. The mean somal areas, total dendritic lengths, and spine densities were compared between groups of neurons, and these showed significant differences across cell types. These measures were also dramatically affected by colchicine, which appears to induce the formation of new dendritic appendages, swelling of the soma, and reduction of dendritic length. Whether colchicine is acting directly upon cytoskeletal structures or indirectly by altering the physiology of the cell is unclear. However, the precise effects of colchicine on mean somal area, total dendritic length, and spine density appear to be dependent upon individual cell type. Colchicine may therefore act in a nonspecific, but nonetheless highly selective, manner in disrupting an endogenous mechanism regulating the number, morphology, and location of spines.
Positive feedback by autoexcitatory neuropeptides in neuroendocrine bag cells of Aplysia
Authors: Brown RO , Mayeri E
Published: March 2018

Neurohormones are often secreted in large amounts from neuroendocrine cells during episodes of synchronous, repetitive spike activity. We report evidence that this pattern of activity in the neuroendocrine bag cells of Aplysia involves positive feedback by autoexcitatory transmitters. Intracellular stimulation of individual bag cells caused slow depolarizing afterpotentials and synchronous afterdischarges in the entire population of bag cells. Application of the bathing medium collected during bag cell activity mimicked these responses. Application of alpha-, beta-, or gamma-bag cell peptides (BCPs), 3 structurally related neuropeptides released from bag cells, also mimicked these responses. These autoexcitatory BCPs fulfill most of the strict criteria necessary for classification as neurotransmitters in this system. This is the first biological activity reported for beta- and gamma-BCPs and brings to 4 the number of bag cell neuropeptides derived from the egg-laying hormone/BCP precursor that are putative cotransmitters. Positive feedback by autoexcitatory transmission may provide a general mechanism for the generation of episodic activity in neuroendocrine systems.
Calpain I activation is specifically related to excitatory amino acid induction of hippocampal damage
Authors: Siman R , Noszek JC , Kegerise C
Published: March 2018

Sustained stimulation of receptors for excitatory amino acids leads to both activation of the calcium-dependent cysteine protease calpain I and to the death of receptive neurons. Here, we have examined the relationship between the calpain I activation and neurodegeneration. Calpain I activation was manifested as increased levels of the major proteolytic fragments of the calpain substrate spectrin, detected and quantified by immunoblotting. Intraventricular administration of the excitatory amino acids kainate or N-methyl-D-aspartate (NMDA) produced calpain I-mediated spectrin degradation and hippocampal neuronal loss. The NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid selectively blocked NMDA- but not kainate-induced protease activation and hippocampal damage. Temporally, spectrin degradation preceded the onset of pyramidal cell degeneration monitored by silver- impregnation histochemistry. Only those doses of kainate (0.15–1 microgram) or NMDA (40–80 micrograms) sufficient to cause hippocampal damage markedly increased spectrin breakdown. Both the neuronal damage and calpain I activation induced by kainate occurred primarily in area CA3. Degeneration of hippocampal neurons evoked by colchicine was not accompanied by calpain activation, indicating that proteolysis is not stimulated simply as a secondary response to neuronal destruction. Thus, a close correspondence exists between excitatory amino acid induction of neuronal degeneration and of calpain I-mediated spectrin degradation. The results suggest that calpain I may be an intracellular mediator of excitatory amino acid action, and further, they support the hypothesis that calcium influx and calpain I activation are obligatory events in the initiation of excitatory amino acid neurotoxicity.