bluuebunny/crossref_metadata_2025 huggingface dataset:
Etazolate (SQ20009): electrophysiology and effects on [3H]flunitrazepam binding in cultured cortical neurons
Authors: Barnes DM , White WF , Dichter MA
Published: March 2018

The actions of etazolate (SQ20009) on cultured cortical neurons have been examined in electrophysiological experiments and in receptor binding studies. Etazolate (0.3 to 100 microM) prolongs the duration of spontaneously occurring IPSPs. Higher concentrations of etazolate produce an increase in membrane chloride conductance, an effect which is picrotoxinin and bicuculline sensitive. Etazolate potentiates the response to exogenously applied GABA and acts synergistically with diazepam to enhance GABA-mediated conductance. Etazolate does not increase glycine-mediated conductance changes. Etazolate increases [3H]flunitrazepam binding and stimulates the GABA enhancement of [3H]flunitrazepam binding. In addition, GABA stimulates the etazolate enhancement of [3H]flunitrazepam binding. The etazolate-mediated increases in binding are Cl- dependent and picrotoxinin and bicuculline sensitive. The dose response relationships for etazolate-mediated effects are similar in physiological experiments and in binding studies. These data suggest that etazolate interacts with the postsynaptic GABA receptor complex at a site distinct from either the GABA recognition site or the benzodiazepine binding site to enhance GABA-mediated inhibition and to increase benzodiazepine binding.
Position-dependent motor innervation of the chick hindlimb following serial and parallel duplications of limb segments
Authors: Whitelaw V , Hollyday M
Published: March 2018

In this paper we report investigations of the innervation of duplicated limb segments to test whether the addition of limb segments along the proximodistal axons could stimulate the growth of appropriate motoneurons into double occurrences of these muscles. Our evidence indicates that it does not. Using retrograde horseradish peroxidase nerve-tracing techniques and reconstructions of experimental limbs, we investigated the motor projection to parallel and serially duplicated legs. In all cases, host limb segments were normally innervated. In a control experiment involving a host thigh connected to a graft calf, the innervation of both segments was normal. In serially duplicated limb segments, however, we found abnormal innervation. In limbs of the type thigh-thigh-calf-foot, the innervation of the second thigh was accomplished by calf motoneurons. In limbs consisting of thigh-calf- calf-foot, the duplicated calf was served by foot motoneurons. The general pattern was that muscles were innervated as a function of their position along the proximodistal axis, irrespective of their identity. In no limb were axons found distal to the third limb segment even before the period of normal cell death. Despite the mismatched innervation with regard to the thigh/calf/foot distinction, axons retained their characteristic selectivity for either dorsally or ventrally derived muscles. The findings suggest that the projection of axons along the proximodistal axis of the limb is influenced by proximal growth cues associated with the formation of the limb plexus as well as by competitive interactions in the distal limb tissue.
Frequency-selective adaptation: evidence for channels in the vestibulo- ocular reflex?
Authors: Lisberger SG , Miles FA , Optican LM
Published: March 2018

The vestibulo-ocular reflex (VOR) is under long-term adaptive regulation to minimize retinal image slip during head movement; normally this process keeps VOR gain (eye velocity divided by head velocity) near 1.0. It has been common to think of the adaptive mechanism as a single pure gain element, although some properties of the system (e.g., frequency-selective changes in the gain of the VOR) argue that it must be more complex. We now report new observations on the frequency selectivity of the adaptive mechanism. Our data suggest a new model in which the VOR operates as a series of parallel, temporal frequency channels, each of which has an independently adjustable gain element. Adaptive changes were produced by oscillating monkeys sinusoidally at a single temporal frequency (0.2 or 2.0 Hz) in visual conditions that cause either increases (toward two) or decreases (toward zero) in VOR gain. When tested in darkness at the adapting frequency, the VOR showed large changes in gain and little or no change in phase. When tested at frequencies other than the adapting frequency, the VOR showed less pronounced changes in gain and unexpected changes in phase. The phase changes were orderly but depended in a complex way on adapting frequency, testing frequency, and VOR gain. We have tested the channels concept by calculating the response properties of a mathematical model that processed its inputs in parallel pathways. The model reproduced our data when we assumed that the vestibular primary afferents were distributed in an orderly way to parallel brain channels that had differing dynamics: vestibular inputs with more phase lead projected to higher frequency channels, which themselves had faster dynamics than their low frequency counterparts. Such an organization, when regulated by an adaptive controller that can selectively alter the gain of one channel, could play a key role in establishing and maintaining the frequency-independent performance seen in the adult VOR.
Termination of afferent axons in macaque striate cortex
Authors: Blasdel GG , Lund JS
Published: March 2018

We used horseradish peroxidase (HRP) to orthogradely label afferent axons in macaque striate cortex. Of the 38 axons that we recovered, nine were recorded intracellularly before being filled with HRP. Light microscope and computer reconstructions of filled processes reveal highly stereotyped patterns of arborization and suggest that there are at least five discrete populations of lateral geniculate nucleus (LGN) afferent axon: (1) those to layer 4C beta, which have extremely circumscribed, dense terminal fields (small branches of which occasionally intrude into 4C alpha) but which have not been shown to project to other laminae; (2) afferents to layer 4A, which in some cases send fine ascending collaterals into layer 2–3 and which do not, apparently, send collaterals to other laminae; (3) afferents to layer 1, which are fine, extend over large distances horizontally, and send collaterals to layer 6A; (4) afferents to the lower two-thirds of layer 4C alpha, which have few or no collaterals in layer 6; and (5) afferents to the upper half of layer 4C alpha, which have arborizing collaterals in layer 6B. Of the nine axons that were recorded intracellularly, those with projections to layer 4C beta (two axons) and to layer 1 (one axon) had color-selective properties, whereas those (six axons) which arborized in 4C alpha all had transient, broad band and highly contrast-sensitive receptive fields. These properties are consistent with derivations from somata in the parvocellular and magnocellular divisions of the LGN, respectively. Afferents to 4C alpha were found to cover approximately 6 times as much surface area as afferents to 4C beta. The preterminal trunks of all axons were found to follow tortuous paths through the neuropil--paths that may derive from axon segregation during development. The wide ranging, patchy distributions of single afferents in 4C alpha suggest that individual 4C alpha axons supply more than one ocular dominance stripe. In one case where the terminal arborization of a 4C alpha axon was mapped against the transneuronally determined pattern of ocular dominance, three separate patches of terminal boutons were indeed found to coincide with the bands of one eye.
Pressure microinjection of nerve growth factor and anti-nerve growth factor into the nucleus and cytoplasm: lack of effects on neurite outgrowth from pheochromocytoma cells
Authors: Seeley PJ , Keith CH , Shelanski ML , Greene LA
Published: March 2018

Exogenous proteins have been introduced into naive and nerve growth factor (NGF)-primed pheochromocytoma cells by pressure microinjection. Microinjection of cells did affect NGF-induced neurite outgrowth by these cells over periods of up to 3 days. Injected NGF failed to elicit neurite outgrowth or regeneration in the absence of extracellular NGF and failed to enhance it in its presence. Injected anti-NGF IgG failed to inhibit neurite outgrowth or regeneration induced by extracellular NGF. Similar results were obtained for both nuclear and cytoplasmic injections.
Increase in nociceptive input to spinocervical tract neurons following chronic partial deafferentation
Authors: Sedivec MJ , Ovelmen-Levitt J , Karp R , Mendell LM
Published: March 2018

Recordings from antidromically identified spinocervical tract (SCT) cells in the partially deafferented spinal cord of chloralose- anesthetized cats have revealed reorganization of their input from peripheral receptors in the skin. Immediately after dorsal rhizotomy of segments L5, L6, S1, and S2, (sparing L7), units in L6 had a lower than normal probability of responding to moderate pressure, mechanical nociceptive, noxious heat, and cooling inputs. This persisted for about 6 weeks, after which normal or even larger than normal proportions of SCT units could be driven by these inputs. The proportion of units driven by hair deflection remained large throughout this period. Responses in the L7 segment with intact L7 dorsal root were unchanged. We suggest that afferent fibers from different receptor types differ in the extent of their normal functional projection, accounting for the selective changes after acute deafferentation. The chronic changes may reflect a differential ability of surviving afferent fibers to undergo compensatory changes in their projection (e.g., sprouting) after chronic rhizotomy.
Morphological classification of rat cortical neurons in cell culture
Authors: Kriegstein AR , Dichter MA
Published: March 2018

Neurons in “mature” (4- to 6-week-old) dissociated cell cultures of 15- day gestational age rat fetal cortex were injected with Lucifer Yellow in order to compare their detailed morphological features with those of cortical neurons in situ, and in order to determine which features of cellular morphology were dependent on local environmental conditions. Neurons were characterized by their cell form (pyramidal, multipolar, fusiform, etc.), dendritic branching pattern, spine density, and axonal projections. The neurons in culture appeared to display all the morphological features seen in cortical neurons in situ. These characteristics appeared to be independent of whether an individual neuron grew in a dense or sparse region of the culture. In addition, examination of neurons during early differentiation indicated that many of their morphological features developed as soon as the neurons could be recognized and before extensive synapse formation occurred.
Slowing of the axonal transport of neurofilament proteins during development
Authors: Hoffman PN , Lasek RJ , Griffin JW , Price DL
Published: March 2018

We examined age-dependent changes in neurofilament transport in motor axons of the rat sciatic nerve. SDS-PAGE and gel fluorography confirmed that the distribution of labeled neurofilament triplet protein coincides with the major slow component a (SCa) wave in these neurons. The velocity of neurofilament transport was calculated on the basis of the location of the 50th percentile Of radioactivity in this wave 33 days after motor neurons were labeled by the intraspinal administration of [3H]leucine and [3H]lysine. Overall, the velocity fell from 1.95 mm/day at 3 weeks of age to 1.12 mm/day at 20 weeks. Between 3 and 10 weeks, it fell at a 6-fold higher rate (0.096 mm/day/week) than between 10 and 20 weeks (0.016 mm/day/week). We also found a marked change in the shape of the slow component wave during development. It appeared to consist of several overlapping peaks moving at slightly different velocities in animals 10 weeks of age or less as compared to a single slower moving peak at 20 weeks. We propose that the velocity of slow axonal transport reflects the level of maturation of the neuron, and that the presence of several overlapping peaks Of transported radioactivity in the sciatic nerve of younger animals reflects the presence of several populations of motor axons at different stages of development. We also discuss the relationship between changes in the velocity of neurofilament transport and alterations in the composition of the cytoskeleton that occur as the axon grows in caliber during postnatal development.
Transmembrane orientation of an early biosynthetic form of acetylcholine receptor delta subunit determined by proteolytic dissection in conjunction with monoclonal antibodies
Authors: Anderson DJ , Blobel G , Tzartos S , Gullick W , Lindstrom J
Published: March 2018

The transmembrane topology of acetylcholine receptor (AChR) delta subunit, synthesized in vitro and co-translationally integrated into dog pancreas rough microsomal membranes, was studied using limited proteolysis and domain-specific immunoprecipitation. Forty-four kilodaltons (kd) of the 65-kd delta subunit comprise a single fragment that is inaccessible to exhaustive proteolytic digestion from the cytoplasmic surface of the membrane by trypsin, chymotrypsin, thermolysin, and pronase. Previously, we have shown that this 44-kd “protected” fragment contains the amino terminus of the intact molecule and all of the core oligosaccharides (Anderson, D.J., P. Walter, and G. Blobel (1982) J. Cell Biol. 93: 501–506). Here we demonstrate that this domain can be further dissected into a 26-kd fragment, together with low molecular weight material, when the membranes are rendered permeable to trypsin by low concentrations of deoxycholate (Kreibich, G., P. Debey, and D. D. Sabatini (1973) J. Cell Biol. 58: 436–462). This 26-kd fragment contains all of the core oligosaccharides present on the intact subunit and therefore constitutes at least part, if not all, of the extracellular domain. The remaining low molecular weight material may derive from the membrane-embedded domain; our data imply that as much as 18 kd may be internal to the lipid bilayer. On the other hand, part of the cytoplasmic pole of AChR-delta can be recovered as a discrete, 12-kd fragment upon mild trypsinization of intact vesicles. We have used this 12-kd fragment to identify anti-AChR-delta monoclonal antibodies (mAbs) that react with the cytoplasmic domain of this subunit. Partial proteolytic fragmentation of the AChR in vitro translation products, in topologically well defined rough microsomes, may be used as a general assay to characterize the domain specificity of anti-AChR mAbs. For example, in the case of AChR-beta, we were able to identify two mAbs that recognize extracellular and cytoplasmic fragments, respectively.
Effect of depolarizing agents on choline acetyltransferase and acetylcholinesterase activities in primary cell cultures of spinal cord
Authors: Ishida I , Deguchi T
Published: March 2018

In cultured neurons dissociated from the spinal cord of fetal mouse, high concentrations of KCl (47 mM) increased choline acetyltransferase (CAT) activity up to 5.5-fold but suppressed acetylcholinesterase (AChE) activity to less than half the level of control cells. Veratridine (3 microM) also increased CAT activity 1.6-fold and suppressed AChE activity to the same level as that induced by high KCl. The increase of CAT activity by the depolarizing agents was blocked by Ca2+ antagonists (verapamil and high Mg2+) and in a low Ca2+ medium, whereas the suppression of AChE activity by high KCl was restored by the same procedures. The synthesis of radiolabeled acetylcholine from [14C]choline was also enhanced 4-fold by incubating cells in high KCl medium. Although the uptake of L-[3H]leucine and [14C]choline into the cells was slightly enhanced by high KCl medium, neither the total amount of protein nor the incorporation of L-[3H]leucine into protein was increased by high KCl medium. These observations indicate that depolarization increased CAT activity in a specific manner, that the activities of CAT and AChE changed inversely under several conditions, and that the effect of depolarization presumably was mediated by the entry of Ca2+ into neuronal cells. The findings raise the possibility that trans-synaptic input could play a crucial role in the development of the activity of cholinergic neurons in spinal cord.
The topography of cytogenesis in the developing retina of the cat
Authors: Rapaport DH , Stone J
Published: March 2018

We have studied the pattern of cytogenesis in the developing retina of the cat, by observing mitotic cells in sections and whole mounts of the retinae of animals between the ages of E (embryonic day) 29 and P (postnatal day) 20. The whole mounts were prepared with the mitotic or ventricular layer uppermost; all of the mitotic cells in this layer could then be surveyed. In retinae from animals up to E46, mitotic cells were present in the ventricular layer at densities of 1000 to 3000 cells/mm2, and their density did not vary consistently with position in the retina. Thus cell division occurs throughout the retina at these ages, with an approximately constant spatial density. By E50, cytogenesis begins to cease and there is a significant pattern to the cessation. Initially, mitotic activity ceases over a small region of retina at the site of the developing area centralis. The nonmitotic area then increases with age, comprising the central 30 to 50% of the retina at birth and the whole of the retina by P10. The pattern of cessation of cytogenesis is closely coincident in space and time with the development of the outer plexiform layer and the maturation of the ganglion cell layer described in previous studies. These patterns presumably contribute to the regional variations in structure apparent in the adult retina.
Regeneration of an identified central neuron in the cricket. I. Control of sprouting from soma, dendrites, and axon
Authors: Roederer E , Cohen MJ
Published: March 2018

When the axon of the medial giant interneuron (MGI) of the cricket is axotomized close to the cell body, the normally stable, characteristic dendritic arborization is induced to sprout supernumerary neurites. The origin of the induced dendritic sprouts is not random; they emerge preferentially from the dentritic tips and branches close to the exit of the axon from the terminal ganglion. If any growth also occurred from the axon, there was a reciprocal relationship between the extent of dendritic and axonal sprouting. On the other hand, axotomy distant to the cell body induces sprouting only from the axon and does not alter the dendritic structure of the MGI. After crushing the ventral nerve cord distant to the cell body, the MGI sprouted neurites from the proximal axonal stump which crossed the site of lesion and continued growing within the distal cord. After a distant cut of the cord, however, the axonal neurites formed a neuroma in the proximal cord stump at the site of lesion and stopped elongating after 1 month. At this time, supernumerary sprouts first began to emerge from the normally smooth, rounded contours of the cell body. Based on these observations, we propose that axotomized neurons produce membrane at a constant rate. This newly synthesized membrane is preferentially inserted into neurites emerging from the proximal axonal stump. When axonal neurites stop growing in a neuroma following a distant cut, then this new membrane appears as supernumerary neurites from the soma. After a close cut, the axon often dies back into the ganglion and appears unable to receive the full complement of sprouting membrane. In such cases, the balance of the newly synthesized membrane is inserted into the dendrites and the characteristic structure of the arborization is significantly altered.
Storage of serotonin in vivo as a complex with serotonin-binding protein in central and peripheral serotonergic neurons
Authors: Gershon MD , Liu KP , Karpiak SE , Tamir H
Published: March 2018

Serotonin-binding protein (SBP) is a soluble protein found in synaptic vesicles of central and peripheral serotonergic neurons. Experiments were undertaken to determine whether serotonin (5-HT) is physiologically stored as a complex with SBP in vivo. [3H]5-HT was used as a probe. Neurons were allowed to specifically take up the labeled amine and attempts were made to recover the in vivo formed [3H]5-HT X SBP complex. Rats were perfused intraventricularly (3 hr) with [3H]5- HT. Strips of rabbit enteric nervous system (ENS) were incubated with [3H]5-HT in the presence of desipramine. The tissues were then homogenized so as to disrupt synaptic vesicles; protein-bound [3H]5-HT was obtained from the 100,000 X g supernatant by filtration on Sephadex G-50 and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Studies with [3H]5-HT added just prior to homogenization indicated that the [3H]5-HT X SBP complex had formed intraneuronally, prior to homogenization. The protein X [3H]5-HT complexes from brain and gut migrated on the gels with apparent molecular weights of 45,000 and 56,000, corresponding to those measured by SDS-PAGE for purified SBP; however, the 45-kilodalton (kd) molecule predominated when the SBP complex was formed in vivo, whereas the 56-kd molecule predominated when the SBP X [3H]5-HT complex was formed with extracted SBP. It is possible that the 56-kd SBP is characteristic of the molecule in perikarya or nonterminal axons, whereas the 45-kd molecule is characteristic of terminal varicosities because radioautographic results show that in both the central nervous system and ENS, [3H]5-HT is mostly concentrated in terminals. In any case, newly taken up [3H]5-HT preferentially labels 45-kd SBP. Depletion of endogenous 5-HT by placing animals on a tryptophan-deficient diet increased the amount of exogenous [3H]5-HT bound to SBP in vivo. This suggests that endogenous 5-HT is normally bound to SBP and competes with the [3H]5-HT probe for available binding sites. The binding of 5- HT to SBP within vesicles may be important to reduce the osmotic pressure that would build up in synaptic vesicles if 5-HT were free in solution.
Effects of ascorbic acid, dexamethasone, and insulin on the catecholamine and opioid peptide stores of cultured adrenal medullary chromaffin cells
Authors: Wilson SP , Kirshner N
Published: March 2018

Bovine adrenal medullary chromaffin cells cultured in serum-free medium were examined for changes in their catecholamine and opioid peptide stores following exposure to dexamethasone, ascorbic acid, or insulin for 2 to 12 days. Dexamethasone failed to alter cellular catecholamine levels, measured by high performance liquid chromatography with electrochemical detection, or cellular opioid peptide content, measured by an enkephalin radioreceptor assay. Chromaffin cells cultured in medium supplemented with ascorbic acid retained high ascorbate contents for 2 to 3 days, despite the rapid loss of this vitamin from the culture medium (approximately 50% lost in 2 hr). The epinephrine and norepinephrine contents of chromaffin cell cultures supplemented with ascorbate for 7 days were increased approximately 10% compared to cultures without added ascorbic acid; ascorbate had no effect on chromaffin cell opioid peptide levels. Addition of insulin to chromaffin cell cultures produced a doubling of cellular protein and opioid peptide levels by 6 days and produced a concentration-dependent increase in the dopamine and norepinephrine contents of the cells with only a slight elevation in cell epinephrine. Chromaffin cells were also tested for the ability to resynthesize their catecholamine and opioid peptide stores following depletion as the result of secretion evoked by acetylcholine or nicotine. The cellular stores of norepinephrine and dopamine were resynthesized within 3 days following secretagogue-evoked depletion. Epinephrine stores were incompletely replenished with only 20% of the epinephrine lost via secretion recovered in 7 days. Opioid peptide levels were maximally recovered (50% of the amount secreted) within 1 day. Addition of ascorbic acid, dexamethasone, or insulin to the medium failed to enhance the recovery of catecholamine stores.
The influence of motor preparation on the response of cerebellar neurons to limb displacements
Authors: Strick PL
Published: March 2018

This study examined the influence of “motor set” on the response of neurons in the deep cerebellar nuclei to peripheral afferent inputs. Two monkeys were trained to perform arm movements which were triggered by imposed displacements of their forelimb. Imposed displacements were generated by a torque motor which was coupled to a handle held by the monkey. The direction of the triggered movements depended on a prior instruction presented to the animal before the onset of the imposed displacement. Single neuron recordings were made from 105 interpositus and 191 dentate neurons whose activity was related to the performance of the task. Forty-three of the interpositus and 46 of the dentate neurons displayed a change in activity within 70 msec of the onset of the imposed displacement. None of these neurons displayed a neural response following the onset of the instruction. The short latency response of most interpositus neurons was related to the parameters of the afferent input generated by the imposed displacements. For more than 60% of the interpositus neurons this response was strongly influenced by the direction of the imposed displacement. None of these responses were markedly altered by the prior instructions. In contrast, the short latency response of 67% of the dentate neurons, although triggered by the imposed displacement, was markedly altered by the “motor set” of the animal. For most of the dentate neurons whose activity was influenced by the animal's “motor set,” the neural response was contingent on two factors: (1) the prior instruction given to the animal and (2) the direction of the imposed displacement. In a second set of dentate neurons (13% of those influenced by motor preparation) the characteristics of the short latency response were determined solely by the nature of the prior instruction. For these neurons the imposed displacement served as a trigger for possible changes in the activity. Thus, dentate neuron activity can behave like a motor command signal which is triggered at short latency by a peripheral event but depends on the intent of the animal.
Characterization of the peptide and sensory neurotoxic effects of capsaicin in the guinea pig
Authors: Buck SH , Walsh JH , Davis TP , Brown MR , Yamamura HI , Burks TF
Published: March 2018

The effects of capsaicin, the major pungent ingredient of hot peppers, were assessed on sensory neuron neuropeptide levels and on sensory function in the adult guinea pig. Systemic doses of capsaicin as low as 2.5 mg/kg depleted substance P (SP) in dorsal roots plus ganglia (DRG) whereas a 10-mg/kg dose depleted the peptide maximally in DRG and in the dorsal spinal cord. High doses of capsaicin had no consistent effects on levels of cholecystokinin (CCK), vasoactive intestinal polypeptide, or somatostatin, although a transient decrease in CCK levels was observed 4 days after dosing. A single 5-mg/kg dose of capsaicin rendered animals completely insensitive to chemical irritation of the cornea without affecting sensitivity to noxious heat. Higher doses of capsaicin produced a marked insensitivity to nociceptive and non-nociceptive heat as well as to chemical irritation without affecting other sensory modalities. The SP depletion and sensory deficits produced by a single 50-mg/kg dose of capsaicin were still evident 10 weeks later. The pattern of selectivity of the sensory deficits produced by capsaicin differed from that produced by morphine which was active against all forms of nociceptive stimuli. The results indicate that in the guinea pig capsaicin is potent at producing a unique, long-lasting syndrome of peripheral sensory deficits that may result from an effect of the agent on SP-containing primary afferent neurons.
Serotonin involvement in descending inhibition of spinal nociceptive transmission produced by stimulation of medial diencephalon and basal forebrain
Authors: Carstens E , MacKinnon JD , Guinan MJ
Published: March 2018

The responses of single lumbar dorsal horn neurons to noxious radiant heat stimuli (50 degrees C, 10 sec) applied to glabrous footpad skin were recorded in cats anesthetized with sodium pentobarbital and 70% N2O. Responses were markedly reduced during electrical stimulation (100- msec trains at 100 Hz, 3/sec, up to 400 microA) at sites in the medial diencephalic periventricular gray (PVG), preoptic area, and basal forebrain. A role for serotonin (5-hydroxytryptamine, 5-HT) was investigated by determining whether descending inhibition from these areas could be affected by (1) acute systemic administration of the 5- HT antagonist methysergide, or (2) depletion of central 5-HT levels by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA; 500 mg/kg, i.p.). Inhibition produced by stimulation at these sites was reduced or abolished in 22 cases following administration of methysergide (0.2 to 1 mg/kg) to non-pretreated cats. In the PCPA- pretreated cats, stimulation in preoptic or basal forebrain areas inhibited the responses of 26 units to noxious skin heating to varying degrees; PVG stimulation inhibited the responses of 14 of 26 units, while the remainder were unaffected. The mean current threshold for inhibition produced by PVG or preoptic/basal forebrain stimulation was significantly higher, while mean inhibition at 200 microA was significantly lower, in units from PCPA-pretreated cats compared to those from non-pretreated cats. The results indicate that 5-HT may be involved in the mediation of spinal inhibition produced by medial diencephalic and basal forebrain stimulation.
Contribution of the cortico-claustral loop to receptive field properties in area 17 of the cat
Authors: Sherk H , LeVay S
Published: March 2018

The contribution of the cat's claustrum to the response properties of cells in area 17 was studied by destroying the left claustrum and examining receptive field properties of cells in both the left and right area 17. For each cell we assessed sharpness of orientation tuning, degree of direction selectivity, length summation, end- stopping, ocular dominance, responsiveness, and several other properties. On the lesioned side, 462 cells were studied, and on the control side, 636 cells. All cats showed a reduction in the number of end-stopped cells in area 17 on the side of the lesion. This was particularly marked in layers 2 + 3 and 4, where end-stopped cells are normally most abundant. In the control hemisphere, 43% of the sample from these layers showed at least moderate end-stopping whereas, in contrast, only 21% exhibited this degree of end-stopping on the side of the lesion. There was no obvious change in other response properties. We conclude that one function of the cat's claustrum is to help regulate the length selectivity of cells in area 17.
Astrocyte-like glia in the peripheral nervous system: an immunohistochemical study of enteric glia
Authors: Jessen KR , Mirsky R
Published: March 2018

The similarities between the enteric nervous system of the gut and the central nervous system (CNS), both of which function as complex integrative nervous networks, include striking ultrastructural similarities between the glia of the enteric nervous system and the astrocytic glia of the CNS. In this paper we have determined whether this anatomical resemblance also extends to the molecular level by examining the enteric glial cells to see whether they express several surface and intracellular molecules which are highly restricted to glia and to astrocytes in particular. Indirect immunofluorescence was used to visualize the antigens in frozen sections of gut wall and in whole mount, tissue culture, and freshly dissected preparations of myenteric and submucous plexuses from rats of various ages. It was found that enteric glial cells expressed the intracellular proteins glial fibrillary acidic protein, glutamine synthetase, and vimentin both in situ and in culture. The surface antigen Ran-2 was expressed in situ but not in culture, and the surface antigen Ran-1 was expressed in culture but not in situ. Cultured enteric glial cells did not express fibronectin in significant quantity, nor did they make galactocerebroside. From these results we conclude that the adult phenotype of enteric glia in situ closely resembles that of astrocytes, while in culture some of their cell surface features change, reverting to those seen during development. Because these cells possess distinctive molecular features and numerically form one of the major populations of peripheral glia, it is appropriate to classify them as a third distinctive category of peripheral glial cells, in addition to satellite and Schwann cells. The molecular similarities between these cells and astrocytes, in addition to their anatomical resemblance, suggest that a further study of enteric glia will provide new insights into the role of glia in integrative nervous tissues.
Specific influence of striatal target neurons on the in vitro outgrowth of mesencephalic dopaminergic neurites: a morphological quantitative study
Authors: Denis-Donini S , Glowinski J , Prochiantz A
Published: March 2018

In previous studies, we have shown that dissociated dopaminergic neurons from embryonic mouse in co-culture with striatal target neurons take up and synthesize dopamine to a greater extent. We now report that striatal target cells influence the morphology of dopaminergic neurons as well. In co-culture, the total length of neuritic arborization visualized by autoradiography is reduced when compared to cultures of mesencephalic neurons alone or to co-cultures with cerebellar cells. Experiments performed in the presence of striatal glial cells at the same density as striatal neurons or with media conditioned with striatal glia or neurons suggest that striatal neurons regulate dopaminergic afferent growth in vitro through specific neuro-neuronal interactions.
The parcellation of the medial geniculate body of the cat defined by the auditory response properties of single units
Authors: Calford MB
Published: March 2018

Single unit responses were recorded in the medial geniculate body (MGB) of anesthetized cats. In response to acoustical stimulation the properties of response latency, discharge pattern, frequency tuning, binaural interaction, and habituation were examined to allow an appraisal of the differentiation of the MGB by electrophysiological means. It is found that definite boundaries can be determined at which there is a distinct change in response properties; the position of these “physiological boundaries” seems to correspond with the boundaries between the seven subnuclei of the MGB described by Morest (Morest, D. K. (1964) J. Anat. 98: 611–630) in Golgi-stained material. Using these physiological boundaries to determine unit locations, population comparisons are made allowing the description of each subnucleus in terms of its auditory response properties. It is suggested that these properties, together with the limited information gained from Nissl cytoarchitecture, are sufficient to describe the location of physiological recording sites in the MGB.
Electrical characteristics of dendrites and dendritic spines in intracellularly stained CA3 and dentate hippocampal neurons
Authors: Turner DA , Schwartzkroin PA
Published: March 2018

Theoretical parameters of synaptic efficacy were studied in a detailed cable model of in vitro hippocampal neurons. CA3 pyramidal cells (n = 9) and dentate granule neurons (n = 6) were injected with horseradish peroxidase (HRP) after brief physiological analysis. The dendrites of these HRP-stained neurons were measured and approximated by a series of cylindrical segments. Specific electrical values of the neurons were calculated on a steady-state basis, using a cable analysis of the dendritic segments. The evaluation was expanded to include idealized dendritic spines. Average spine dimensions were determined by electron microscopic measurements. The density distribution of spines was patterned after reported Golgi measurements of similar neurons. The average electrotonic length of the CA3 apical dendrites was determined to be 0.69 length constant. These CA3 neurons were not well approximated by a single equivalent cylinder coupled to a soma (E-C model). The dentate granule cells exhibited an average electrotonic length of 1.12 length constants and could be adequately represented by the E-C model. Synaptic efficacy was estimated by the transfer of either charge or steady-state voltage from a spine input to the soma. Charge transfer varied as a function of the electrotonic distance from the soma to the input site. Voltage transfer, however, did not vary as a simple function of electrotonic distance. Voltage and charge transfer averaged less than 10% loss across the dendritic spine neck. These calculations, based on specific neuronal anatomy, predict that dendritic spines do not significantly attenuate steady-state electrical signals.
Modulation by vasoactive intestinal peptide (VIP) of serotonin receptors in membranes from rat hippocampus
Authors: Rostene WH , Fischette CT , McEwen BS
Published: March 2018

The vasoactive intestinal peptide (VIP) has been located in various structures of the rat brain, but few actions of the peptide have been reported as yet. Because VIP might interact with classical neurotransmitter systems in the central nervous system as it does in the periphery, we investigated whether VIP can modulate serotonin (5- HT1) receptors in membrane preparations obtained from brain areas which contain various amounts of VIP and 5-HT receptors. The presence of bacitracin alone, which protects VIP from proteolytic degradation, decreases the affinity of [3H]5-HT binding in almost all of the structures tested. Scatchard analysis indicates that, in the presence of bacitracin, VIP significantly decreases the affinity and increases the number of specific high affinity binding sites for [3H]5-HT in the dorsal hippocampus. VIP induces a dose-dependent increase in the number of 5-HT1 receptors with a maximal response of 60% with 10(-7) M VIP. At the same concentration, neither secretin nor glucagon modifies 5-HT1 receptor density. No effect of VIP is observed in the ventral hippocampus, parietal cortex, whole hypothalamus, and midbrain. This effect of VIP is not observed when bacitracin is omitted, and the presence of calcium ions does not alter the efficacy of the VIP effect. No effect of VIP is obtained on [3H]spiperone binding assayed with 10 microM mianserin to define specific binding. The present data suggest that some of the effects of 5-HT in the hippocampus may be modulated by VIP.
Post-translational modification and evoked release of two large surface proteins of sympathetic neurons
Authors: Sweadner KJ
Published: March 2018

Two high molecular weight glycoproteins, exposed on the surface of sympathetic neurons, are modified after they have been translated, glycosylated, and inserted in the plasma membrane. B1 (apparent Mr = 230,000 by electrophoresis in sodium dodecyl sulfate) and B3 (Mr approximately 200,000) are each modified to give proteins of lower apparent molecular weight: B2 (Mr approximately 215,000) and B4 (Mr approximately 185,000). B1 and B3 are derived from two precursors, P1 (Mr approximately 210,000) and P3 (Mr approximately 185,000) which are nonsialylated, mannose-rich proteins not exposed on the cell surface. In unstimulated cells, B1 and B3 are converted to B2 and B4 with a half- life of 4 to 6 hr. In cells which have been treated chemically to evoke the release of neurotransmitter, the modification appears to be accelerated, and B2 and B4 are shed into the medium in soluble form (S2 and S4). This evoked release of protein is calcium dependent and is detected only in conditions which favor the rapid release of neurotransmitter. In the absence of exogenous calcium, however, transmitter release can be evoked without the accompanying release of protein. Thus the release of protein is not an essential step of transmitter release, but may follow it. B1, its precursor, and derivatives are immunologically related to the NILE (nerve growth factor-inducible, large external) glycoprotein of pheochromocytoma PC12 cells (McGuire, J. C., L. A. Greene, and A. V. Furano (1978) Cell 15: 357–365). B3 does not cross-react with B1 or NILE antigenically, but otherwise is synthesized, processed, and released in a similar manner.
Single-channel currents activated by curare in cultured embryonic rat muscle
Authors: Morris CE , Wong BS , Jackson MB , Lecar H
Published: March 2018

Single cholinergic receptor channel currents activated by curare were recorded in tissue-cultured embryonic rat muscle, directly confirming curare's action as a weak cholinergic agonist. In embryonic muscle, curare, in addition to its classical action as a competitive cholinergic antagonist, produces small sustained depolarizations which can be blocked by alpha-bungarotoxin. The single-channel events are of short duration but otherwise exhibit the major features observed with other cholinergic agonists. The single-channel events are blocked by alpha-bungarotoxin. Two values of unit conductance, 30.4 +/- 3.5 pS and 47 +/- 6 pS, were measured in cells from different cultures. Histograms of open-state duration are well fit by a distribution which is a sum of two exponentials, with time constants of 0.33 +/- 0.08 msec for the fast component and 1.84 +/- 0.43 msec for the slow component.
Binaural characteristics of units in the owl's brainstem auditory pathway: precursors of restricted spatial receptive fields
Authors: Moiseff A , Konishi M
Published: March 2018

The barn owl uses binaural phase and intensity differences for sound localization. These two cues also determine the receptive fields of specialized neurons in the inferior colliculus. The main aim of this study was to investigate where neuronal sensitivity to the binaural cues emerges in the brainstem auditory nuclei, and how this sensitivity reaches the neurons in the inferior colliculus. The owl's phase- sensitive neurons are selective to microsecond phase differences of high frequency signals, unlike mammalian phase-sensitive neurons which are restricted to low frequency signals. In certain nuclei virtually all of the neurons are sensitive to either phase differences or intensity differences, but not to both. These nuclei form two distinctly separate pathways that converge at the inferior colliculus where neurons selective to both phase and intensity differences occur. In contrast to the mammalian auditory system, the owl's phase- and intensity difference-sensitive pathways are not segregated into low frequency and high frequency channels.
Visual response properties in the tectorecipient zone of the cat's lateral posterior-pulvinar complex: a comparison with the superior colliculus
Authors: Chalupa LM , Williams RW , Hughes MJ
Published: March 2018

The medial portion of the cat's lateral posterior-pulvinar complex (LPm) receives a prominent ascending projection from the superficial layers of the superior colliculus. This region of the thalamus has been suggested to serve as a relay by which visual information from the midbrain could be conveyed to extrastriate cortex. In order to determine how the functional organization within the LPm compares with that of the superior colliculus, visual response properties of LPm and superior collicular neurons were examined under identical experimental conditions. The majority of neurons in the LPm, as in the superior colliculus, respond vigorously to moving stimuli, and a substantial proportion of these cells also exhibit a preference for movements in a particular direction. Furthermore, most cells in the LPm, in common with those of the tectum, respond only in a phasic manner to flashed stimuli, have homogeneous receptive field organization, and show response suppression to stimuli larger than the activating region of the receptive field. As in the colliculus, the ipsilateral visual field is represented in the LPm. In spite of these similarities, there are also some striking differences between the visual responses of LPm and collicular neurons. First, the average size of receptive fields of neurons within the LPm is at least twice that of units in the superficial gray layers of the tectum. Second, more cells in the colliculus are directionally selective than those in the LPm, and the distribution of preferred directions is different in the two regions. Third, an appreciable proportion (27%) of the cells in the LPm are orientation selective, whereas this response property is only rarely encountered in the cat's tectum. Fourth, many LPm neurons can only be activated by binocular stimulation, whereas most collicular units respond equally well to stimulation of either eye. Collectively, these findings indicate that there is a substantial transformation in the lateral posterior-pulvinar complex of the ascending visual influx provided by the superior colliculus.
The medial division of the medial geniculate body of the cat: implications for thalamic organization
Authors: Winer JA , Morest DK
Published: March 2018

The structure of neurons and axons was studied in the medial division of the medial geniculate body of the cat with the Golgi methods. The results show that the medial division consists of morphologically heterogeneous neurons. The main types, in descending order of frequency, are medium-sized neurons with (1) radiate, (2) tufted, or (3) elongate dendrites; (4) small stellate or radiate neurons, including Golgi type II cells with a locally arborizing, sparsely branching axon collateral system; (5) large neurons, which are weakly tufted. A variety of afferent axons impose a reticulate appearance on the fiber architecture of the medial division. The dominant element in the neuropil consists of axons terminating in the medial division as well as a collateral system of fibers traveling to the adjacent ventral and dorsal divisions of the medial geniculate body. Four types of extrinsic axons are described, including two kinds of thin axons with collateral systems, thick fibers with restricted branches, and large axons with elaborate, serpentine collaterals. Compared to the dorsal and ventral divisions of the medial geniculate body, where, respectively, radiate and tufted neurons are more frequent, the medial division is intermediate in a sense-not that the degree of radiate or tufted dendritic branching is less well developed, but neither type of cell predominates. Moreover, all of the cell types are overlapping in distribution, although the large ones tend to be more common rostrally in the medial division. Likewise, there is no clear-cut regional segregation of axonal types. The ascending projections to the medial division originate in many different structures, involving purely auditory tracts from the inferior colliculus, spinal inputs, and pathways from polysensory regions, such as the midbrain tegmentum and deep layers of the superior colliculus. The spinothalamic tract projects most heavily to the rostromedial region of the medial division bordering the ventrobasal complex. The auditory input from the central nucleus of the inferior colliculus tends to project more heavily to the caudolateral region next to the ventral nucleus of the medial geniculate body. However, these inputs overlap in the medial division. Moreover, the pathways from the tegmentum and the superior colliculus have a broad distribution in the medial division. Still other inputs are known, not to mention those from the cerebral cortex and a widespread and complicated pattern of thalamocortical projections.(ABSTRACT TRUNCATED AT 400 WORDS)