bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific changes in rapidly transported proteins during regeneration of the goldfish optic nerve
Authors: Benowitz LI , Shashoua VE , Yoon MG
Published: March 2018

Double labeling methods were used to identify changes in the complement of proteins synthesized in the retinal ganglion cells and transported down the optic nerve during the process of axonal regeneration. Eight to 62 days after goldfish underwent a unilateral optic nerve crush, one eye was labeled with [3H]-, the other with [14C]proline. Control and regenerating optic nerves were dissected out and homogenized together after 5 hr, a time which allowed us to examine selectively membrane- bound components which migrate in the rapid phase of axoplasmic transport. Proteins from the two sides were so-purified and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analysis of the 3H and 14C incorporation patterns along the gels revealed a radical shift away from the normal labeling spectrum during regeneration, with selective changes in labeling at particular molecular weights varying over a 3-fold range. Eight days after crushing the optic nerve, the greatest increases in labeling were seen for material with apparent molecular weights of 24,000 to 27,000, 44,000, and 210,000 daltons. These peaks declined thereafter, and on days 29 to 39, the most prominent increases were at 110,000 to 140,000 daltons. These studies indicate a continuously changing pattern in the synthesis and/or degradation of proteins that are rapidly transported down the optic nerve during regeneration and point to molecular species potential significance in the establishment of the visual map upon the brain.
Transmitter release properties along regenerated nerve processes at the frog neuromuscular junction
Authors: Decino P
Published: March 2018

Reinnervation following nerve crush was examined in the frog cutaneous pectoris muscle using histological and electrophysiological techniques. Functional recovery, as monitored by miniature endplate potential (mepp) frequency and quantal content, was slower than morphological recovery. To understand this discrepancy, extracellular recording electrodes were used to determine the amount of transmitter released from localized areas of nerve terminals in both unoperated and experimental muscles. There was no increased tendency over controls for the proximal portion of a regenerated nerve process to release more quanta (spontaneous or nerve evoked) than the distal portion. Moreover, extracellular recording at the growing nerve tip showed that this portion of nerve terminal was capable of transmitter release upon nerve stimulation. These results suggest that the entire length of a regenerating nerve terminal becomes functional at early stages of reinnervation and matures at essentially the same rate.
Nerve growth factor-induced differentiation of PC12 cells: evaluation of changes in RNA and DNA metabolism
Authors: Gunning PW , Landreth GE , Layer P , Ignatius M , Shooter EM
Published: March 2018

The relationship between both DNA and RNA metabolism and the nerve growth factor (betaNGF)-induced differentiation of PC12 cells was investigated. Cells remained in log phase growth for 4 days after exposure to betaNGF. DNA synthesis was similarly unaffected by betaNGF during this time. Thereafter, a gradual decrease in DNA synthesis was observed. In contrast, as many as 40% of the cells display neurites after 4 days exposure to betaNGF. The implication, that cells which have begun to differentiate morphologically may still synthesize DNA, was confirmed using autoradiography. The cellular RNA concentration was elevated significantly within 1 day of exposure to betaNGF and continued to increase for up to 6 days. Dose-response analysis revealed that this increase in cellular RNA, both rRNA and tRNA, closely correlates with the size and number of neurites per cell rather than with the cell's capacity to grow a neurite per se. A parallel rise in the cellular protein concentration was observed also. It was concluded, therefore, that (1) cessation of cell division is not a prerequisite for the initiation of the morphological differentiation of these cells and (2) the elevation of the cellular RNA content influences some quantitative aspects of neurite outgrowth.
Characteristics of growth-associated polypeptides in regenerating toad retinal ganglion cell axons
Authors: Skene JH , Willard M
Published: March 2018

We report here certain properties of three polypeptides that are rapidly transported in greatly increased amounts during the regeneration of toad optic nerves. All three of these growth-associated polypeptides (GAPs) are associated with a membrane(s) with a buoyant density similar to the plasma membrane. Since none of these GAPs are solubilized substantially by washing the membranes in either low or high ionic strength media, they may be ″integral membrane proteins. All three GAPs contain a significant number of polar amino acids (judging from their isoelectric points and their rapid electrophoretic migration under their native charge), suggesting that portions of each molecule must extent away from the membrane surfaces. One of these proteins (GAP- 50) is a fucosylated glycoprotein. GAP-50 and GAP-43 appear to be transported preferentially to axon tips; GAP-24 may be distributed more uniformly along the axons. GAP-24 has an extremely short half-life (4 to 6 hr), while the maximum half-lives of GAP-43 (2 to 3 days) and GAP- 50 (approximately 1 day) are longer. We discuss the relevance of these properties to possible roles for these polypeptides in the control of nerve regeneration.
Aspartate and glutamate as possible neurotransmitters in the visual cortex
Authors: Baughman RW , Gilbert CD
Published: March 2018

To identify possible neurotransmitters in the visual cortex, high pressure liquid chromatography was used to measure the release of endogenous compounds from a tissue slice preparation of the visual cortex of the rat. When synaptic release was induced, either by raising the K+ concentration in the medium or by adding veratridine, of the compounds measured, marked increases (6- to 35- fold) in release rate were observed for aspartate, glutamate, and gamma-aminobutyric acid (GABA). This increased release was blocked either with a low Ca2+/high Mg2+ or a tetrodotoxin-containing medium. To label possible aspartate or glutamate pathways, D-[3H]aspartate and D-[3H]glutamate were injected in the lateral geniculate nucleus (LGN), superior colliculus, and visual cortex. Following injections in the LGN, labeling was observed in the pyramidal cells in cortical layer 6 and in a diffuse band in layer 4, whereas no cortical cells were labeled after injections in the superior colliculus. When D-[3H]aspartate was injected in the cortex, the uptake again was concentrated in the layer 6 cells, but not labeled cell bodies were seen in the LGN, confirming the specificity of the uptake and retrograde filling process. Diffuse labeling was present in the LGN, however, presumably produced by anterograde filling process. Diffuse labeling was present in the LGN, however, presumably produced by anterograde transport from the layer 6 cells. These results suggest that layer 6 cells in the cortex, which are the source of the recurrent projection to the thalamus, may use aspartate or glutamate as their transmitter. Analysis of the function of the corticothalamic pathway may be facilitated by these findings.
Biochemical identification of pharmacologically and functionally distinct GABA receptors in rat brain
Authors: Browner M , Ferkany JW , Enna SJ
Published: March 2018

Receptor binding studies were undertaken in an attempt to identify and characterize pharmacologically and functionally distinct receptor sites for gamma-aminobutyric acid (GABA) in rat brain. The results indicated that the potency of bicuculline, a GABA receptor antagonist, to displace membrane-bound [3H]GABA varies significantly among different brain regions, with the greatest potency found in the cerebral cortex and midbrain. In addition, in the presence of 50 mM ammonium thiocyanate, the potency of bicuculline to displace specifically bound [3H]GABA was increased significantly, with the magnitude of this increase being greater in some brain areas than others. The biological relevance of this thiocyanate-induced shift in the potency of bicuculline to inhibit [3H]GABA binding was indicated by the finding that ammonium thiocyanate also increased the potency of bicuculline to inhibit GABA-activated benzodiazepine receptor binding, a biochemical measure of GABA receptor function. Receptor site saturation analysis revealed that ammonium thiocyanate selectively abolished the high affinity GABA binding site without affecting either the low affinity component or GABA-activated benzodiazepine receptor binding. These findings provide further evidence for the existence of pharmacologically distinct GABA receptor sites, with some being more sensitive to the blocking action of bicuculline than others. Furthermore, the data provide direct evidence to support the hypothesis that only low affinity GABA receptor sites are linked to the benzodiazepine receptor, indicating that the kinetically different GABA binding sites are also functionally distinct. The discovery that ammonium thiocyanate selectively destroys high affinity GABA receptor binding may be useful for further defining the pharmacological, biochemical, and functional differences between GABA receptors in brain.
Glycine receptor: light microscopic autoradiographic localization with [3H]strychnine
Authors: Zarbin MA , Wamsley JK , Kuhar MJ
Published: March 2018

Glycine receptors have been localized by autoradiography in the rat central nervous system (CNS) using [3H]strychnine. The gross distribution of receptors is in excellent accord with the distribution determined by filtration binding assays. Specifically, the density of glycine receptors is greatest in the gray matter of the spinal cord and decreases progressively in regions more rostral in the neuraxis. Glycine receptors were found to be associated with both sensory and motor systems in the CNS. Moreover, there is a striking correlation between areas of high strychnine binding site density and areas in which glycine has been found to be electrophysiologically active. Finally, the anatomic localization of strychnine binding sites may help explain many of the signs and symptoms of strychnine ingestion. For example, individuals consuming subconvulsive doses of strychnine frequently experience altered cutaneous and auditory sensation. We have localized strychnine receptors in areas of the acoustic system known to influence discriminative aspects of audition and in areas of the spinal cord and trigeminal nuclei which modulate discriminative aspects of cutaneous sensation. The alteration of visceral functions (e.g., blood pressure and respiratory rate) associated with strychnine ingestion may be accounted for in a similar manner.
Plasticity in the spinal cord sensory map following peripheral nerve injury in rats
Authors: Devor M , Wall PD
Published: March 2018

The medial part of the L4 and 5 dorsal horn in adult rats is dominated by afferents from the toes and foot. After transection of the sciatic and saphenous nerves, virtually all cells in this region are left without any peripheral receptive field. Beginning 4 to 5 days after nerve section, however, many peripherally deafferented cells take on a novel receptive field on the thigh, lower back, or perineum. The new receptive fields are served by intact nerves ending in proximal skin rather than by misdirected sprouts of cut toe-foot nerves. Thus, peripheral axotomy results in synaptic reorganization in the spinal cord proper. Receptive field reorganization occurs after nerve transection, ligation, or ligation with distal transection but does not occur if the nerve is crushed. If a cut nerve is sutured and regeneration is permitted, spinal reorganization is reversed and the toe-foot afferents regain exclusive dominance of the medial dorsal horn.
Dual expression of neurotransmitter synthesis in cultured autonomic neurons
Authors: Iacovitti L , Joh TH , Park DH , Bunge RP
Published: March 2018

Previous studies have demonstrated that, when the predominantly adrenergic neurons of the neonatal rat superior cervical ganglion (SCG) are grown under certain culture conditions, they acquire many of the properties characteristic of cholinergic neurons. To determine whether this occurs at the expense of certain of their adrenergic properties, cultured SCG neurons were characterized by both biochemical and immunocytochemical methods. We report here data which demonstrate that sympathetic neurons, cultured under conditions which foster the accrual of cholinergic properties, exhibit parallel increases in the activities and amounts of the specific adrenergic enzymes, tyrosine hydroxylase and dopamine beta-hydroxylase, as well as the specific cholinergic enzyme, choline acetyltransferase. Using immunocytochemical methods, we further demonstrate that essentially all SCG neurons stain positively with antibodies to tyrosine hydroxylase, even at times in culture when choline acetyltransferase levels are elevated significantly. These data indicate that virtually all SCG neurons grown in our culture system are capable of dual neurotransmitter production and thus express at least the potential for dual function for up to 7 weeks in culture.
Enhancement of heart rate responses during conditioning and sensitization following interruption of raphe-spinal projections
Authors: Cabot JB , Goff DM , Cohen DH
Published: March 2018

Recent evidence suggests that neurons within the ventromedial medulla give rise to an inhibitory pathway(s) which projects directly upon the sympathetic preganglionic neuropil. The present investigations were initiated to determine the effects of interrupting this pathway on the expression of a learned autonomic response, defensively conditioned cardioacceleration in the pigeon. Experiment I included two groups. Each experimental animal was trained concomitantly with a sham-operated control, and all birds received 100 trials of conditioning. Each conditioning trial consisted of a 6-sec light presentation followed immediately by a 0.5-sec foot shock. The first experimental group included birds with lesions involving the rostral medullary raphe nuclei (RMR), while the second included birds sustaining lesions of the caudal pontine raphe region (CPR). The principal findings were that (a) RMR-lesioned birds exhibited heart rate increases significantly greater than CPR-lesioned and control birds, (b) heart rate changes in CPR- lesioned birds were not significantly different from control values, and (c) RMR and CPR lesions did not affect base line heart rates significantly. Experiment II was undertaken to determine whether the elevated responsivity following RMR lesions represented a performance increment or an actual enhancement of associative learning. RMR- lesioned animals and their paired controls received 60 trials of sensitization training (explicitly unpaired lights and foot shocks) followed by 60 trials of conditioning. The primary result was that, independent of the training paradigm, RMR-lesioned animals, had significantly greater heart rate increases than control animals. In summary, the “lability” of heart rate changes following RMR lesions apparently is a performance effect and does not represent an enhancement of associative learning. Additionally, the data are consistent with the hypothesis that lesions of this midline medullary region disrupt a descending pathway important for the phasic reflex modulation of chronotropic cardiac responses to exteroceptive stimuli.
Localization of sodium channels in cultured neural cells
Authors: Catterall WA
Published: March 2018

Sodium channels in cultured neural cells were localized by light microscopic autoradiography of specifically bound 125I-scorpion toxin. Ninety percent of the cell-bound 125I-scorpion toxin was associated specifically with sodium channels as assessed by the blocking of autoradiographic labeling by unlabeled scorpion toxin and by depolarization. Sodium channels were distributed uniformly in the surface membrane of neurites and cell bodies of both morphologically differentiated and undifferentiated cells of clone N18 of mouse neuroblastoma C1300. Sodium channels were distributed nonuniformly in many cultured spinal cord neurons. Visual observation indicated that 37 +/- 5% of cultured spinal cord neurons had a higher sodium channel density on the initial segment of one or more neurites than on the cell body. For these neurons, the density on one neurite initial segment averaged 7.4 +/- 1.9-fold greater than on the adjacent cell body. This increased sodium channel density may be the basis of the lower threshold for action potential generation at the axon initial segment of motor neurons and some spinal interneurons in vivo.
Developmental stage-specific changes in lectin binding to mouse cerebellar cells in vitro
Authors: Huck S , Hatten ME
Published: March 2018

Eleven fluorescein isothiocyanate-conjugated (FITC) lectins, each with distinct carbohydrate-binding properties, were used to assess cell surface glycoconjugates of embryonic and early postnatal cerebellar cells in vitro. Fluorescence staining of embryonic day 13 (E13) cerebellar cells with FITC Ricinus communis agglutinin diminished markedly between 24 and 72 hr in vitro. No staining of postnatal day 0 (P0) or postnatal day 7 (P7) cells was observed with FITC Ricinus communis agglutinin. A similar, but less pronounced decrease in FITC concanavalin A, FITC Lens culinaris, and FITC wheat germ agglutinin was observed between embryonic day 13 and birth. No specific staining of E13, P0, or P7 cultures was observed with FITC peanut agglutinin, FITC Dolichos bifloris agglutinin, FITC soybean agglutinin, FITC Wistaria floribundis agglutinin, FITC Phaseolus vulgaris agglutinin, FITC Limulus polyphemus agglutinin, or FITC Ulex europaeusI agglutinin. Similar results were obtained with 125I-lectin binding assays. Ricinus communis 125-I-agglutinin binding decreased dramatically between embryonic day 13 and birth. Less pronounced decreases were observed in 125I-concanavalin A and wheat germ 125I-agglutinin binding. Very low levels of soybean 125I-agglutinin or Ulex europaeusI 125I-agglutinin were bound by either embryonic or early postnatal cerebellar cells in vitro.
The influence of attentive fixation upon the excitability of the light- sensitive neurons of the posterior parietal cortex
Authors: Mountcastle VB , Andersen RA , Motter BC
Published: March 2018

We describe the effect of behavioral state upon the excitability of light-sensitive (Ls) neurons of the inferior parietal lobule, area 7a, studied in waking monkeys. The responses of parietal LS neurons to visual stimuli are facilitated during the state of attentive fixation of a target light as compared to their responses to physically and retinotopically identical test stimuli delivered during the eye pauses of alert wakefulness. Seventy percent of the neurons tested (n = 55) showed significant increments in responses in the state of attentive fixation; the median value of the increments was 3.5 times. Only 4 of the 55 cells examined completely showed the reverse relation. Three sets of control experiments were done. The facilitation occurred when the responses evoked during the trials of a reaction task with attentive fixation of a target were compared with those evoked by identical stimuli delivered to the same retinotopic locations at the end of each intertrial interval: the facilitation of attentive fixation is not due to a shift in the general level of arousal. The facilitation occurred when the animal maintained attentive fixation of a spot of the tangent screen without a target light or when an additional light mimicking the target light was presented along with testing stimuli in the state of alert wakefulness without attentive fixation: the facilitation is not produced by a sensory-sensory interaction between target and testing lights. Finally, the facilitation was observed whether or not the test stimuli were behaviorally relevant. We conclude that the act of attentive fixation exerts a specific and powerful effect upon the excitability of the neural systems linking the retinae and the inferior parietal lobule and that the facilitation plays an important role in visually guided behavior.
An autoradiographic study of the projections of the central nucleus of the monkey amygdala
Authors: Price JL , Amaral DG
Published: March 2018

The efferent connections of the central nucleus of the monkey amygdala have been studied using the autoradiographic method for tracing axonal projections. Small injections of 3H-amino-acids which are largely confined to the central nucleus lead to the labeling of several brainstem nuclei as far caudally as the spinomedullary junction. Specifically, in the forebrain, the central nucleus projects heavily to the bed nucleus of the stria terminalis, the basal nucleus of Meynert, the nucleus of the horizontal limb of the diagonal band, and more lightly to the substantia innominata and the preoptic area. In the hypothalamus, label is found over the dorsomedial nucleus, the perifornical region, the lateral hypothalamus, the supramammillary area, and most heavily in the paramammillary nucleus. In the thalamus, all components of the nucleus centralis medialis and the nucleus reuniens receive fibers from the central nucleus and there is a light projection to the medial pulvinar nucleus. In the mesencephalon, there is heavy labeling dorsal to the substantia nigra ad over the peripeduncular nucleus and lighter labeling within the substantia nigra pars compacta and the ventral tegmental area; the midbrain central gray is also labeled. More caudally, fibers from the central nucleus travel in the lateral tegmental reticular fields and contribute collaterals to the raphe nuclei, the cuneiform nucleus, and the central gray substance. Perhaps one of the heaviest terminal zones is the parabrachial region of the pons, both the lateral and the medial nuclei of which receive a prominent central nucleus projection. Only the ventral aspect of the adjacent locus coeruleus appears to receive a substantial input, but there is labeling also over the area of the nucleus subcoeruleus. Finally, there is heavy labeling around the dorsal motor nucleus of the vagus and over the parvocellular component of the nucleus of the solitary tract. A number of intra-amygdaloid connections between the basal and lateral nuclei of the amygdala and the central nucleus are also described. The present findings, taken together with recently reported widespread projections from the temporal association cortex to the amygdala, point out a potentially trisynaptic route between neocortical association regions and a variety of brainstem nuclei, many of which are related to autonomic function.
Cellular localization of the molecular forms of acetylcholinesterase in rat pheochromocytoma PC12 cells treated with nerve growth factor
Authors: Inestrosa NC , Reiness CG , Reichardt LF , Hall ZW
Published: March 2018

In rat pheochromocytoma (PC12) cells treated with nerve growth factor (NGF), there are several molecular forms of the enzyme acetylcholinesterase (AChE) which sediment on sucrose density gradients at 4 to 6, 10, and 16 S, respectively. We have investigated the cellular localization of these forms in PC12 cells. In order to determine which forms are soluble and which are membrane bound, we extracted PC12 cells in buffers of various ionic strengths and detergent compositions. To distinguish internal from external forms of the enzyme, we examined the effect of di-isopropyl fluorophosphate and BW284c51 dibromide, membrane-permeable and -impermeable inhibitors of AChE, respectively, AChE forms in intact cells. We also determined the susceptibility of the forms in intact cells to collagenase treatment. Based on these studies, we conclude that the globular G1 and G2 (4 to 6 S) forms are internal and consist of both soluble and membrane- associated species. Thirty percent of the G4 (10 S) form is bound to cytoplasmic membrane structures, while the remainder occurs as an integral component of the plasma membrane. The asymmetric A12 (16 S) form is also a surface protein but is extracted by high salt without detergent and is released from intact cells by collagenase. This form thus contains a collagenous domain and is located outside of the plasma membrane, where it may be associated with an extracellular matrix.
Visual responses of single neurons in the caudal lateral pulvinar of the macaque monkey
Authors: Benevento LA , Miller J
Published: March 2018

Single unit recordings were made in the portion of the lateral pulvinar which forms the lateral aspect of the caudal pole of the thalamus, i.e., PL gamma (Rezak, M., and L. A. Benevento (1977) Soc. Neurosci. Abstr. 3:573; Rezak, M. (1978) Soc. Neurosci. Abstr. 4: 642), of macaque monkeys. PL gamma receives convergent inputs from the occipital cortex and has strong reciprocal interconnections with the visual association cortex, including the inferotemporal cortex (areas 20 and 21). It was found the that PL gamma has a poor or nonexistent retinotopic organization. Many of the neurons had large, unflanked, overlapping receptive fields which often included the fovea. A few neurons could be influenced by a visual stimulus placed anywhere in the visual field described by a tangent screen. The receptive fields could be bilateral or located entirely within the contralateral or ipsilateral hemifields. The majority of units were binocular and exhibited various types of binocular interaction which could be quite complex. The binocular response was not predictable from the algebraic sum of the monocular responses and could be of the opposite sign (e.g., excitatory when the monocular response was inhibitory). Neurons which were also sensitive to the direction of movement of stimuli projected upon the tangent screen formed a major group. Of the units sensitive to tangentially moving stimuli, two special subgroups were found. One group of neurons gave sustained responses to static levels of luminance, while the other group was sensitive to simuli which moved toward or away from the eyes. The nonlinear rate of change of the apparent size of approaching or receding stimuli was described by a mathematical function which also describes the response of the neurons to the same stimuli. For many of these units which were sensitive to tangentially moving stimuli and one other class of stimuli, such as luminance levels of movement in depth, the responses to one class were seemingly unrelated to the responses to the other class. The same statement may be made for monocular and binocular responses. It may be, then, that different wiring diagrams describe these different types of inputs. These physiological results are discussed in terms of the inputs to PL gamma as well as its cortical targets.
Immunocytochemical localization of vasoactive intestinal polypeptide- containing cells and processes in the suprachiasmatic nucleus of the rat: light and electron microscopic analysis
Authors: Card JP , Brecha N , Karten HJ , Moore RY
Published: March 2018

The distribution of vasoactive intestinal polypeptide-like (VIP) immunoreactivity in neurons and processes within the suprachiasmatic nuclei (SCN) of the rat was investigated with light and electron microscopic immunocytochemical techniques. These studies utilized well characterized antisera directed to synthetic vasoactive intestinal polypeptide. Specificity was established by absorption of the antisera with synthetic vasoactive intestinal polypeptide. Neurons and dendrites exhibiting specific VIP immunoreactivity are concentrated in the ventral half of the nucleus, with the greatest concentration of immunoreactive perikarya occurring in the ventral SCN immediately adjacent to and within the optic chiasm (OC). Thin varicose axons containing VIP immunoreactivity are present throughout the SCN. A large number of immunoreactive axons leave the dorsal aspect of the SCN to reach the periventricular hypothalamic nucleus and continue dorsally to form an extensive plexus along the ventral border of the paraventricular hypothalamic nucleus. Other immunoreactive axons project upon the contralateral SCN via the OC. Ultrastructurally, VIP- containing neurons in the SCN are characterized by a spherical to slightly elongated soma and an invaginated nucleus that fills the majority of the cell body. In the soma, peroxidase reaction product is localized on the outer membrane of all cellular organelles. The reaction product of immunoreactive boutons is related primarily to vesicles, and some of these boutons establish axodendritic synaptic contacts in the SCN. The demonstration of VIP-containing neurons in the SCN provides further evidence that this nucleus is composed of a heterogeneous population of neurons which form distinct subfields within it.
The induction of "stress" proteins in organ slices from brain, heart, and lung as a function of postnatal development
Authors: White FP
Published: March 2018

The proteins synthesized in vitro by rat brain, heart, and lung slices were compared by two-dimensional polyacrylamide gel electrophoresis. A protein, P71, which is related to one of the heat shock proteins induced in many cultured cells by hyperthermia and other harsh conditions, was the major protein synthesized by all slices from rats 3 weeks old and older. In vivo synthesis of P71 was not detected in brain, heart, or lung from these animals nor was there any detectable Coomassie brilliant blue-stained protein coinciding with P71 on the gels. P71 thus appears to be a minor protein species in normal unstressed brain, heart, and lung. While both heart and lung slices synthesized large quantities of P71 at all stages of postnatal development, brain slices synthesized little, if any, P71 until 3 weeks postnatal. There was a dramatic decrease in protein synthesis in all tissue slices during postnatal development. During this decrease, the relative abundance of newly synthesized P71 remained almost constant in heart and lung slices, but the relative abundance of P71 increased by approximately 50-fold in brain slices. The cells synthesizing P71 in brain slices were enriched in a microvascular fraction. The increase in P71 synthesis by these cells, occurring between the 3nd and 3rd postnatal week, coincides with the final maturation of brain capillaries and the blood-brain barrier.
Collateralization of monoamine neurons: mesotelencephalic dopamine projections to caudate, septum, and frontal cortex
Authors: Fallon JH
Published: March 2018

Axonal collateralization of substantia nigra (SN) and ventral tegmental area (VTA) neurons was studied in the rat with the multiple retrograde labeling technique using fluorescent dyes. Injections of nuclear yellow, granular blue, and propidium iodide were made into the caudate- putamen, septum, and frontal cortex and cells were found to be single, double, and triple labeled in the SN-VTA. Cells in the VTA were predominantly single labeled with the three tracers and cells in the medial SN were predominantly double labeled with the tracers. These results suggest that mesotelencephalic neurons in the SN-VTA can be subdivided into two subpopulations on the basis of relative degree of collateralization. The SN axons appear to be highly collateralized to anatomically and functionally distinct telencephalic areas and the VTA axons appear to have a more singular one-to-one type of projection to the same forebrain regions.
Neuronal cell surfaces: distinctive glycoproteins of cultured adrenergic and cholinergic sympathetic neurons
Authors: Braun SJ , Sweadner KJ , Patterson PH
Published: March 2018

Cell surface components which are candidates for a role in nerve-target interactions specific for neurons of particular transmitter types in the sympathetic nervous system have been identified. Neurons of superior cervical ganglia of neonatal rats were dissociated and cultured in the virtual absence of non-neuronal cells under conditions previously found to control their choice of neurotransmitter. When raised in medium conditioned by heart cells, the neurons become cholinergic; when raised in medium which depolarizes them, the neurons remain in their original adrenergic state. The cell surface proteins of the neurons were labeled by either metabolic or surface-specific methods, separated by two-dimensional polyacrylamide gel electrophoresis, and visualized by autoradiography. A total of approximately 35 glycoproteins can be resolved, of which at least 14 are exposed on the cell surface. We evaluated glycoproteins of neurons raised under conditions which differ in their potency for inducing cholinergic properties: medium conditioned by skeletal muscle, liver, or heart cells or medium containing 1 mM butyric acid. The expression of three neuronal glycoproteins was correlated with the ability of a given culture condition to induce the synthesis and accumulation of acetylcholine or catecholamines. Two of these proteins are exposed on the cell surface, and the third appears to be identical with a protein previously shown to be secreted into the culture medium.
Encoding of target range and its representation in the auditory cortex of the mustached bat
Authors: O'Neill WE , Suga N
Published: March 2018

The time course of acoustic events is a critical element for the recognition of biologically meaningful sounds. Echolocating bats analyze the time intervals between their emitted biosonar pulses and the echoes returning from objects to assess target distance (range). In this study, we have explored the auditory cortex of the mustached bat, Pteronotus parnellii rubiginosus, using pairs of acoustic stimuli mimicking the multiharmonic biosonar signals (pulses) used by this species and their echoes. A discrete field of auditory cortex dorsorostral to the tonotopically organized primary field contains neurons which are insensitive to pure tone, frequency-modulated (FM), or noise stimuli presented singly. Rather, they respond strongly to pairs of stimuli, specifically, the fundamental FM component of the pulse paired with an FM component of one of the higher harmonics of the echo. We call these neurons FM1-FMn facilitation neurons. There are three separate longitudinal clusters in this cortical area containing FM1-FM2, FM1-FM3, and FM1-FM4 neurons, respectively. Moreover, FM1-FMn neurons are specifically sensitive to the time delay between the two FM components, i.e., the time delay of the echo from the pulse. Thus, they can decode target range. Two types of delay-sensitive neurons were found. Tracking neurons, whose response to echo delay varied according to repetition rate and stimulus duration, were found rarely. Delay- tuned neurons, which were tuned to specific time delays (best delays) of the echo from the pulse, were much more evident. Both types of neurons are organized into columns with similar best delays, and the best delay of delay-tuned neurons was found to increase systematically along the cortical surface in the rostrocaudal direction. This area, therefore, contains a neural representation of target range along this best delay axis. Such an axis exists in each of the clusters of FM1- FM2, FM1-FM3, and FM1-FM4 neurons. This is a new type of cortical organization which is not tonotopic but which represents an important acoustic cue related to the time course of acoustic events.
Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex
Authors: Bienenstock EL , Cooper LN , Munro PW
Published: March 2018

The development of stimulus selectivity in the primary sensory cortex of higher vertebrates is considered in a general mathematical framework. A synaptic evolution scheme of a new kind is proposed in which incoming patterns rather than converging afferents compete. The change in the efficacy of a given synapse depends not only on instantaneous pre- and postsynaptic activities but also on a slowly varying time-averaged value of the postsynaptic activity. Assuming an appropriate nonlinear form for this dependence, development of selectivity is obtained under quite general conditions on the sensory environment. One does not require nonlinearity of the neuron's integrative power nor does one need to assume any particular form for intracortical circuitry. This is first illustrated in simple cases, e.g., when the environment consists of only two different stimuli presented alternately in a random manner. The following formal statement then holds: the state of the system converges with probability 1 to points of maximum selectivity in the state space. We next consider the problem of early development of orientation selectivity and binocular interaction in primary visual cortex. Giving the environment an appropriate form, we obtain orientation tuning curves and ocular dominance comparable to what is observed in normally reared adult cats or monkeys. Simulations with binocular input and various types of normal or altered environments show good agreement with the relevant experimental data. Experiments are suggested that could test our theory further.
Depolarization-induced release of adenosine 5'-triphosphate from isolated varicosities derived from the myenteric plexus of the guinea pig small intestine
Authors: White TD , Leslie RA
Published: March 2018

In order to study the release of ATP from a neuronal preparation thought to be “purinergic,” isolated varicosities were prepared from myenteric plexus by mincing and homogenizing the longitudinal muscle of guinea pig ileum in 0.32 M sucrose. The presence of varicosities within the crude preparation (P2), isolated by differential centrifugation, was confirmed by electron microscopy and by the presence of occluded lactate dehydrogenase as a cytoplasmic marker. Varicosities were purified further from the P2 fraction on a discontinuous sucrose density gradient and characterized morphologically. Varicosities resembling cholinergic, “purinergic,” and adrenergic axonal terminals were identified. The release of ATP from both crude and purified varicosities was detected by monitoring the light produced when the released ATP reacted with firefly luciferin-luciferase which was present in the incubation medium. Elevated extracellular K+ or Rb+ caused the release of ATP, whereas elevated Na+ and Li+ did not. The release of ATP by either K+ or by the depolarizing drug, veratridine, was Ca2+ dependent. This requirement of extracellular Ca2+ for veratridine-induced release of ATP from isolated myenteric varicosities contrasted strikingly with that for brain synaptosomes, where the release of ATP induced by veratridine was increased rather than decreased in a Ca2+-free medium. The characteristics of ATP release from myenteric varicosities are consistent with a possible neurotransmitter function for ATP in myenteric plexus, although it is also possible that ATP is co-released with some other neurotransmitter.
Modulation of lateral geniculate nucleus cell responsiveness by visual activation of the corticogeniculate pathway
Authors: Marrocco RT , McClurkin JW , Young RA
Published: March 2018

A radial grating stimulus was used to assess the effect of stimulation of the region beyond the classical surround of monkey lateral geniculate nucleus (LGN) receptive fields. The effect was measured by the differences in the responsiveness of the LGN cell center to small flashing spots between two conditions: (1) grating stationary or (2) grating rotating. The grating was present only in regions beyond the classical center and surround. The rotating grating produced changes in the flash-evoked spike response but not in the spontaneous activity in about half of the X cells and all of the Y cells. The direction of the effect was independent of the sign of the receptive field center. In a control experiment, cryogenic blockade of striate cortex reversed the effect in all cells tested. The grating effect was still present for cells having fields in that part of visual space beyond the region represented by the cooled cortical area. The effect was not a result of activation of classical extra-receptive field influences, since cells showing the effect did not exhibit shift or periphery effects or outer disinhibitory surrounds. The effect was not seen in recordings from intrageniculate retinal axons. We conclude that the radial grating effects LGN cell responsivity by activation of the corticogeniculate pathway.
The influence of sex hormones on antidepressant-induced alterations in neurotransmitter receptor binding
Authors: Kendall DA , Stancel GM , Enna SJ
Published: March 2018

Long term (21-day) treatment with antidepressants induces a decrease in beta-adrenergic and serotonin 2 (5-HT2) receptor binding in rat brain frontal cortex. Since hormone imbalances are known to be associated with affective illness, the present study was undertaken to determine whether sex hormones influence these alterations in neurotransmitter receptor binding. Using receptor binding assays, we found that castration abolishes the decline in the concentration of 5-HT2, but not beta-adrenergic, receptors brought on by chronic imipramine or iprindole treatment in both male and female rats. In contrast, the receptor responses to trazodone, mianserin, and pargyline were not influenced by surgery. Furthermore, mianserin was found to reduce beta- adrenergic binding in intact females, but not males, suggesting a sex- related specificity with regard to the response to this agent. Testosterone and estrogen, but not dihydrotestosterone, reversed the effects of castration in males, suggesting that the interaction between the steroids and antidepressants is mediated through estrogenic, rather than androgenic, receptors. The results indicate that the receptor responses to some antidepressant drugs is dependent, at least in part, on the hormonal state of the animals.
Phenotypic expression in the developing murine enteric nervous system
Authors: Rothman TP , Gershon MD
Published: March 2018

The development of the enteric nervous system was examined in fetal mice. Synthesis of [3H] acetylcholine ([3H]ACh) from [3H]choline and acetylcholinesterase histochemistry were used as phenotypic markers for cholinergic neurons, while the radioautographic detection of the specific uptake of [3H]serotonin (5-[3H]HT) and immunocytochemical staining with antiserum to 5-HT marked serotonergic neurons. The gut also was examined by light and electron microscopy. Development of the gut was studied in situ and in explants grown in organotypic tissue culture. Neurons were first detected morphologically in the foregut on embryonic day 12 (E12). Synthesis of [3H]ACh was detectable on days E10 to E12 but increased markedly between days E13 and E14. Uptake and radioautographic labeling by 5-[3H]HT was seen first in the foregut on day E12, in the colon on day E13, and in the terminal colon on day E14. Gut explanted from both distal and proximal bowel prior to the time when neurons could be detected (days E9 to E11) nevertheless formed neurons in culture. These cultures of early explants displayed markers for both cholinergic and serotonergic neurons. Enhances development of both cholinergic and serotonergic neurons was found in cultures explanted at day E11 over that found in cultures explanted on days E9 or E10. The evidence presented indicates (1) that enteric neurons develop from nonrecognizable precursors, (2) that the proximodistal gradient in neuronal phenotypic expression probably is not related to a proximodistal migration of precursor cells down the gut, (3) that the colonization of the bowel by neuronal precursors may be a prolonged process continuing from day E9 at least through day E11, (4) that the first pool of neuronal primordia to colonize the developing bowel can produce both cholinergic and serotonergic neurons. It is proposed that a sequential interaction of a long retained pool of dividing precursor cells with a fetal enteric microenvironment that changes as a function of time during ontogeny may be involved in producing the phenotypic diversity that characterized the enteric nervous system.
Norepinephrine regulation of cerebral glycogen utilization during seizures and ischemia
Authors: Harik SI , Busto R , Martinez E
Published: March 2018

Norepinephrine (NE) depletion of the cerebral cortex after lesion of the ipsilateral locus ceruleus (LC) causes abnormalities of cerebral oxidative metabolism when the cortex is stimulated to increased energy demand (Harik, S. I., J. C. LaManna, A. I. Light, and M. Rosenthal (1979) Science 206: 69–71; LaManna, J. C., S. I. Harik, A. I. Light, and M. Rosenthal (1981) Brain Res. 204: 87–101). These abnormalities were exhibited as decreased mitochondrial reducing equivalent flow. One possible cause of this would be the decreased availability of oxidative metabolic substrates in the NE-depleted cortex. We therefore investigated the effect of unilateral LC lesion and the resultant depletion of ipsilateral endogenous NE on glycogen and other energy metabolites in the cerebral cortex of rats under three conditions: (1) at “rest,” (2) when energy demand is inncreased markedly by seizures, and (3) during total cerebral ischemia. We report no differences in cerebral metabolites between NE-depleted and control hemispheres at "rest." In seizures and ischemia, however, the increase in the level of adenosine 3′:5′-monophosphate (cyclic AMP) and the breakdown of glycogen were impaired considerably in the NE-depleted cortex. The data suggest that depletion of central NE impairs cerebral glycogenolysis in response to increased energy demands and ischemia. Such impairment may be mediated via a cyclic AMP-related mechanism.
Reversible developmental change in the ability of ciliary ganglion neurons to extend neurites in culture
Authors: Collins F , Lee MR
Published: March 2018

From stages 35 to 40 in the chicken embryo, ciliary ganglion neurons undergo a developmental change which is detected in our assay system as a marked decline in the ability to extend neurites when placed in culture. This developmental loss is observed when the neurons are placed in culture as single, dissociated cells or as undissociated ganglion explants. The loss of the ability to extend neurites in culture is not a transitory phenomenon, for no recovery of this ability is observed during the rest of embryonic development or posthatching. There is a close temporal correlation between the embryonic period during which the ability of ciliary ganglion neurons to extend neurites declines and the period (stages 35 to 40) when these neurons form functional peripheral synapses in the embryo. The ability to extend neurites rapidly is not recovered during normal development as long as the ganglion and its connections within the organism remain intact. However, if the ciliary ganglia are removed from a stage 40 embryo and cultured for 3 to 4 days before being dissociated, the neurons have largely recovered their ability to initiate neurite outgrowth rapidly. This recovery after removal from the embryo is also presumably responsible for the eventual dense outgrowth of neurites from stage 40 ganglion explants after a 3- to 4-day delay in culture. Our results, in conjunction with similar results from other systems, suggest a cause and effect relationship between the establishment or disruption of peripheral connections and the loss or recovery, respectively, of the ability to extend neurites rapidly.