bluuebunny/crossref_metadata_2025 huggingface dataset:
The visual claustrum of the cat. I. Structure and connections
Authors: LeVay S , Sherk H
Published: March 2018

The cat's dorsocaudal claustrum was studied in Golgi preparations, by electron microscopy, and by anterograde and retrograde tracer techniques. It receives a convergent retinotopic projection from several visual cortical ares, including areas 17, 18, 19, 21a and PMLS (posteromedial lateral suprasylvian area). The projection arises from spiny dendrite cells (pyramidal and fusiform) in the middle of cortical layer VI. As shown by a double label experiment, they form a separate population from those projecting to the lateral geniculate nucleus. There are also inputs from the lateral hypothalamus, from the nucleus centralis thalami, and probably from the locus coeruleus, but not from the sensory nuclei of the thalamus. Non-visual cortical areas do not project to the visual claustrum, but many of them are connected to other parts of the nucleus. For example, the splenial (cingulate) gyrus projects to a claustral zone just ventral to the visual area, and regions anterior to the visual area are connected with somatosensory and auditory cortex. The commonest cell type in the claustrum is a large spiny dendrite neuron whose axon leaves the nucleus after giving off local collaterals. Small spine-free cells, with beaded dendrites and a locally arborizing axon, are found also. Electron microscopy of the claustrum after ablation of the visual cortex showed degenerating type 1 axon terminals synapsing on spines and beaded dendrites, suggesting a direct cortical input to both cell types. The visual claustrum projects back to the visual cortex, to the same areas from which it receives an input. The return projection is predominantly ipsilateral, but there is, in addition, a small crossed projection. The claustrocortical axons terminate in all cortical layers but most heavily in layers IV and VI. The majority of the cells in the visual claustrum project to the cortex, and retinotopy is maintained throughout the entire corticoclaustral loop. No subcortical projections from the claustrum could be identified.
Postsynaptic localization of alpha 2-adrenergic receptors in rat submandibular gland
Authors: Bylund DB , Martinez JR
Published: March 2018

Norepinephrine is known to inhibit its own release from presynaptic nerve terminals through alpha 2-adrenergic receptors, which presumably have a presynaptic localization. alpha 2-Adrenergic receptors (as determined by [3H]clonidine binding) appear in rat submandibular gland membranes following reserpine treatment. These alpha 2 receptors seem to be localized postsynaptically, based on the following evidence. (1) Partial destruction of the presynaptic nerve terminals with 6- hydroxydopamine did not decrease the density of alpha 2-adrenergic receptors following subsequent reserpine administration. (2) Duct ligation, which results in atrophy of the gland, markedly decreased the density of the receptors following subsequent reserpine administration. (3) Surgical denervation resulted in the appearance of high levels of alpha 2-adrenergic receptors. (4) The changes in alpha 2 receptors paralleled the changes in postsynaptic beta-adrenergic receptor binding (as determined by [3H]dihydroalprenolol). While these results establish the existence of postsynaptic alpha 2-adrenergic receptors in an innervated tissue, the concomitant presence of a low density of presynaptic alpha 2 receptors has not been eliminated.
Possible mechanisms of enkephalin action on hippocampal CA1 pyramidal neurons
Authors: Dingledine R
Published: March 2018

(1) Intracellular and extracellular recordings were made from CA1 pyramidal neurons in an in vitro rat hippocampal slice preparation, while [D-Ala2, D-Leu5]enkephalin (DADL) was applied by perfusion at a known concentration (1 to 5 X 10–7 M), in a small droplet, or by iontophoresis into the cellular and dendritic layers of the slice. The effects of DADL on synaptic potentials and membrane properties were studied in an effort to determine the mechanisms underlying its epileptogenic action in the hippocampus. (2) DADL increased the size and often the duration of excitatory postsynaptic potentials (EPSPs) generated on either the apical or basal dendrites; this resulted in an increased discharge probability for a constant orthodromic stimulus. Extracellular field potential recordings showed a larger population spike for a given size field EPSP. These effects of DADL could be reversed substantially by perfusion with naloxone (1 to 5 X 10–7 M) and appeared qualitatively different from the epileptiform actions of penicillin. (3) DADL did not appear to increase the intrinsic excitability of the soma membrane, since membrane potential, input resistance, spike threshold, and antidromic field potentials all were unchanged. In addition, the shape of the membrane charging curve during hyperpolarizing current injection was not changed noticeably by DADL. (4) At the concentrations tested, DADL did not attenuate recurrent inhibition in the CA1 region, as evaluated by comparing in the absence and presence of DADL: (a) antidromically evoked recurrent inhibitory postsynaptic potentials (IPSPs) and their dependence of membrane potential, (b) the reduction of a synaptically driven population spike by a prior antidromic volley, (c) iontophoretic GABA (gamma- aminobutyric acid) responses. Similarly, IPSPs evoked by orthodromic stimulation appeared either unaffected or occasionally enhanced by DADL. (5) By iontophoretic mapping, it was shown that the DADL- sensitive sites are limited to stratum oriens and stratum pyramidale. Local application of DADL into stratum radiatum was relatively ineffective in enhancing the efficacy of synapses located in this region. (6) The dendritic input-output relationship between the presynaptic fiber volley and the field EPSP was not changed by DADL. This finding and the results of the iontophoretic mapping experiments suggest that increased excitatory transmitter release was not involved. (7) The data are consistent with the proposal that DADL selectively attenuates a dendritic IPSP which is virtually invisible to the soma, although the possibility cannot be ruled out that DADL may, in addition, act to enhance the responsiveness of pyramidal dendritic membrane to excitatory synaptic activation.
Brain peptidase with a unique neuronal localization: the histochemical distribution of dipeptidyl-aminopeptidase II
Authors: Gorenstein C , Tran VT , Snyder SH
Published: March 2018

To assess whether specific peptidases regulate neuropeptide disposition, we have examined histochemically the localization of dipeptidyl-aminopeptidase II (DAP II). With beta-naphthylamide (beta- NA) substrates, this enzyme has a selectivity for lysyl-alanyl-beta-NA. DAP II staining is highly localized to specific neuronal populations with no staining over glia. Areas in the brain with high densities of DAP II staining include the mitral cells in the olfactory bulb, polymorphic cells in the hippocampus, the paraventricular nucleus of the hypothalamus, and the anterior dorsal thalamus, Purkinje cells, and deep nuclei in the cerebellum. Staining occurs in virtually all cell groups in the inferior colliculus, red nucleus, oculomotor nucleus, and mesencephalic nucleus of the trigeminal nerve, the stratum album of the superior colliculus, as well as most cells in the cochlear and superior olivary nuclei. DAP II localizations do not correlate fully with those on any known neuropeptide. Of the numerous peptides evaluated, only glucagon competes substantially for the DAP Ii substrate, reducing enzymatic activity by 50% at a 2 x 10(-5) M concentration.
Substance P receptor on parotid cell membranes
Authors: Liang T , Cascieri MA
Published: March 2018

A conjugate (125I-BH-SP) between substance P and 125I-labeled Bolton- Hunter reagent binds reversibly to a single class of high affinity (Kd = 4 nM) binding sites on dispersed rat parotid cells. The total number of binding sites is 49 +/- 17 fmol/mg of protein. The binding affinity of 13 fragments and analogs of substance P correlates with their relative potency in stimulating salivation. The smallest fragment of substance P which exhibits significant binding affinity and saliva- stimulating activity is the COOH-terminal hexa(6–11)peptide. Structurally unrelated neurotransmitters and hormones do not affect the parotid cell binding of 125 I-BH-SP. 125I-BH-SP pre-bound to the cells was recovered mainly in the particulate fractions of the cell homogenate. The 125I-BH-SP binding activity of the parotid cells was inactivated by pretreatment of the cells with papain but not with ribonuclease A or deoxyribonuclease I. Our results suggest that 125I-BH- SP binds to a substance P receptor on parotid membranes and that the receptor, at least in part, may be a protein.
The distribution of melanin in the developing optic cup and stalk and its relation to cellular degeneration
Authors: Strongin AC , Guillery RW
Published: March 2018

The early distribution of melanin in the developing optic cup and stalk and its relationship to cellular degeneration have been studied during intrauterine development in hamsters, mice, ferrets, and humans. The extensive degenerative changes that occur in the region of the optic fissure do not involve any pigment-bearing cells. Melanin is not formed at the site of the fissure until after the processes of fusion and the associated degenerative changes are complete. In contrast to this, there is a small region near the junction of the cup and stalk where melanin is particularly related to degenerative changes. Melanosomes form dense clumps associated with basophilic, apparently degenerate areas of cytoplasm, and these melanosome complexes themselves undergo further degenerative changes. The two types of degenerative changes, pigmented and unpigmented, are limited to the same two regions of the developing eye in all four species. However, the pigment degeneration is more extensive in ferrets and humans than in mice and hamsters. These observations raise the possibility that the lysis of melanosomes plays a significant but undefined local role in ocular
Axonal ramifications of hippocampal Ca1 pyramidal cells
Authors: Knowles WD , Schwartzkroin PA
Published: March 2018

Intracellular injections of Lucifer Yellow into CA1 pyramidal cells of the in vitro guinea pig hippocampal slice enabled us to examine in detail the morphology of the axons of these neurons. We also recorded the electrophysiological responses of these neurons to alvear stimulation. In our morphological examinations, we found that many axons bifurcate in the alveus, with the major branch projecting caudally toward the subiculum and the second, thinner branch projecting rostrally toward the fimbria. Either axons may bifurcate further to produce several axon branches which follow parallel paths in the alveus. These axons also have local collaterals which project into strata oriens and pyramidale. In addition, a very fine plexus of axonal processes was observed in stratum oriens located largely within the basal dendritic field of the parent cell. Our electrophysiological experiments demonstrated that neurons could be activated antidromically by stimulation of the alveus at sites both rostral ad caudal to the neuron. Weak alvear stimulation occasionally evoked small potentials which appeared similar to fast prepotentials. The local axonal ramifications may be involved in recurrent pathways mediating feedback inhibition and/or excitation. The axonal bifurcations also may provide a basis for understanding the origins of fast prepotentials elicited with antidromic stimulation.
Bilateral organization of the vocal control pathway in the budgerigar, Melopsittacus undulatus
Authors: Paton JA , Manogue KR , Nottebohm F
Published: March 2018

Anatomical and electrophysiological methods were used to map the vocal control nuclei of the budgerigar, Melopsittacus undulatus. Beginning with the motor nucleus of the syrinx, nuclei were located using antidromic stimulation and then injected with horseradish peroxidase (HRP). Retrogradely transported HRP labeled afferents to the injected nucleus. This procedure was repeated at successively higher levels along the vocal pathway. Connections found using this strategy then were confirmed using anterograde transport of HRP and/or tritiated proline and orthodromic electrical stimulation. We found that the primary vocal control pathway consisted of (1) the motor nucleus innervating the trachea and syrinx, nXIIts; (2) an archistriatal nucleus, RA; and (3) a neostriatal nucleus, “HVc.” These nuclei correspond to similar, possibly homologous, nuclei in the vocal control pathway of the canary (Nottebohm, F., T. M. Stokes, and C. M. Leonard (1976) J. Comp. Neurol. 165: 457–486) but, because of differences in gross brain morphology, are displaced considerably in absolute position. Furthermore, the projection from RA to the motor nucleus is bilateral in the budgerigar, whereas the same connection is strictly ipsilateral in the canary. The projection of the motor nucleus to muscles of the vocal organ is also bilateral in the budgerigar (Manogue, K. R., and F. Nottebohm (1981) J. Compl. Neurol., in press) but ipsilateral in the canary. the possible significance of these species differences for lateralization of motor control is discussed.
Classical conditioning in a simple withdrawal reflex in Aplysia californica
Authors: Carew TJ , Walters ET , Kandel ER
Published: March 2018

The ability of Aplysia and other gastropod molluscs to exhibit complex behaviors that can be modified by associative learning has encouraged us to search for an elementary behavior controlled by a simple and well analyzed neural circuit that also can be modified by this type of learning. Toward that end, we have now produced classical conditioning in the defensive siphon and gill withdrawal reflex of Aplysia. We used as a conditioned stimulus (CS) a light tactile stimulus to the siphon, which produces weak siphon and gill withdrawal. As the unconditioned stimulus (US), we used a strong electric shock to the tail, which produces a massive withdrawal reflex. Specific temporal pairing of the CS and US endowed the CS with the ability of triggering enhanced withdrawal of both the siphon and the gill. Random or unpaired presentations of the CS and US, as well as presentations of the CS or US alone, produced either no enhancement or significantly less enhancement than paired presentations of the CS and US. The conditioning is acquired rapidly (within 15 trials) and is retained for several days. The conditioned response is abolished completely by removal of the abdominal ganglion and many of the neurons involved in the conditioning have been identified in this ganglion previously. These include the sensory neurons and several interneurons in the CS pathway and the siphon and gill motor neurons of the conditioned and unconditioned response pathways. Moreover, the sensory neurons of the US pathway have been identified in the pleural ganglia. As a result of its simplicity, it should be possible in this reflex to specify neurons that are causally related to the conditioned response. Since this reflex also exhibits nonassociative learning, it also may be possible to compare associative and nonassociative learning on a mechanistic level.
Stimulation of the gerbil's gustatory receptors by saccharin
Authors: Jakinovich W
Published: March 2018

The gustatory responses from the chorda tympani nerve of the Mongolian gerbil, Meriones unguiculatus, were tested with saccharin and some closely related compounds. Only two compounds, saccharin and 6- chlorosaccharin, stimulated the gerbil's taste receptors to any degree and in the same order in which they are sweet to man, saccharin greater than 5-chlorosaccharin. Those compounds which are tasteless to man did not stimulate and include N-methyl saccharin, phthalimide, and O- sulfobenzoic acid. These nonstimulating derivatives did not inhibit the saccharin electrophysiological response. The saccharin taste response pH optimum is from 5 to 8. At pH 7 and 8, saccharin is fully ionized and is binding to the receptor site by an anionic mechanism. Kinetic plots of the taste response at pH 7 indicate that saccharin is forming 1:1 complexes with it. In addition, mixtures of saccharin and sucrose stimulate in such a manner as to suggest that they are interacting at different receptor sites.
Anomalous anatomy of identified neurons in the larval prawn: spontaneous and induced by microlesions
Authors: Friedlander DR , Levinthal C
Published: March 2018

The abdominal ganglia of the prawn Macrobrachium rosenbergii undergo developmental changes of fundamental interest between the time of hatching and metamorphosis. These changes include an increase in cell numbers and changes in the connectivity between identified neurons. The giant motoneurons involved in the escape response, which form a syncytium in the adult, are observed as separate neurons with crossed axons in early larvae. Anomalous growth and connections of identified neurons were studied in order to gain some understanding of the rules and mechanisms governing normal development. Spontaneous anomalies included: supernumerary axons and abnormal axonal trajectories. The plasticity and specificity of identified neurons were studied by following the anatomical effects of deletions of giant neurons. Microlesions were inflicted reproducibly by means of a focused beam of visible and ultraviolet light. Within a day, irradiated cell bodies are eliminated; complete disappearance of the axon takes about 10 days, indicating that the remarkable ability of some invertebrate neurons to survive without a soma is not present in the larval prawn. As a result of the removal of an axon, the most common effect found in central connections was the absence of the collaterals or axons deprived of their targets. No collateral sprouting was detected in the central nervous system. In about a third of the ganglia where a giant motoneuron was killed and structure was analyzed 2 or more weeks after irradiation, anomalous connections were found. They usually involved contacts between an interneuron deprived of its normal target and the contralateral motoneuron which remained intact. The restricted types of anomalies observed support the notion of a hierarchical order in the rules governing formation of central synapses, in which neuron type ranks higher than laterality.
[14C]2-deoxyglucose uptake in ground squirrel brain during hibernation
Authors: Kilduff TS , Sharp FR , Heller HC
Published: March 2018

Autoradiographic patterns of [14C]2-deoxyglucose uptake are described throughout the brains of hibernating and euthermic ground squirrels. Autoradiographs of the brains of hibernating animals are generally homogeneous in comparison to euthermic animals; hence, the relative 2- deoxyglucose uptake (R2DGU) of gray to white matter for the majority of the 85 neural structures examined decreases during hibernation. Two categories of structures are identified as potentially important in hibernation: (1) structures that have the highest R2DGU during hibernation (cochlear nucleus, paratrigeminal nucleus, and superior colliculus) and (2) structures that undergo the least reduction in R2DGU in the transition from euthermia to hibernation (suprachiasmatic nucleus and lateral septal nucleus). The percentage of reduction in R2DGU that a structure undergoes in the transition from euthermia to hibernation is proportional to the R2DGU of that structure during euthermia. The suprachiasmatic, paratrigeminal, and cochlear nuclei undergo less of a reduction than would be predicted from this relationship and may be particularly important during hibernation. Sensory nuclei that receive primary afferent projections are among the structures with the highest R2DGU during hibernation. These metabolically active structures may be responsible for the sensitivity of the hibernator to environmental stimuli.
Depletion of somatostatin-like immunoreactivity in the rat central nervous system by cysteamine
Authors: Sagar SM , Landry D , Millard WJ , Badger TM , Arnold MA , Martin JB
Published: March 2018

Selective neurotoxins have been of value in providing a means for specifically interfering with the actions of endogenous neurotransmitter candidates. Others have shown cysteamine (CSH) to deplete the gastrointestinal tract and hypothalamus of rats of immunoreactive somatostatin, suggesting a toxic action of that compound directed against somatostatin-containing cells. The present study further defines the actions of cysteamine on somatostatin in the central nervous system. (CNS). Cysteamine hydrochloride administered subcutaneously results in a depletion of somatostatin-like immunoreactivity (SLI) in the retina, brain, and cervical spinal cord of rats. The effect is demonstrable at doses of 30 mg/kg of body weight and above, occurs within 2 to 4 hr of a single injection of the drug, and is largely reversible within 1 week. The mean depletion of SLI observed within the CNS varies from 38% in cerebral cortex to 65% in cervical spinal cord 24 hr following administration of CSH, 300 mg/kg of body weight, s.c. By gel permeation chromatography, all molecular weight forms of SLI are affected, with the largest reductions in those forms that co-chromatograph with synthetic somatostatin-14 and somatostatin-28. These results indicate that CSH has a generalized, rapid, and largely reversible effect in depleting SLI from the rat CNS.
Preferential localization of polyribosomes under the base of dendritic spines in granule cells of the dentate gyrus
Authors: Steward O , Levy WB
Published: March 2018

Electron microscopic studies of the dentate gyrus of the rat have revealed an apparent association between polyribosomes and dendritic spines. The present study was designed to elucidate the nature of this association. Our qualitative observations revealed that polyribosomes appeared primarily in two locations within the dendrite: (1) beneath the base of identified spines just subjacent to the intersection of the spine neck with the main dendritic shaft and (2) beneath mounds in the dendritic membrane which had the appearance of the base of a spine which extended out of the plane of section. To quantitatively define the nature of the apparent association, we attempted to determine (1) the proportion of spines with associated polyribosomes and (2) the proportion of the polyribosomes within dendrites which are associated with spine bases. Evaluation of profiles which were identifiable as spine neck-dendritic shaft intersections in a single section revealed that an average of 12.2% had associated polyribosomes. A serial section analysis revealed a somewhat higher incidence, however. Of a collection of 34 through-sectioned spines, 29% had polyribosomes which were revealed in one or more of the sections comprising the series. To evaluate what proportion of polyribosomes within the dendrite was associated with spines, we evaluated a series of photographs covering approximately 1250 micrometer2 of the dentate molecular layer from five animals, identifying all polyribosomes within dendrites and scoring their location as being (1) under spines, (2) under mounds, or (3) other. An average of 9.6% of the polyribosomes were found under processes identifiable as spine neck-dendritic shaft intersections, while 71.4% of the polyribosomes were found under mounds. Only 19% were not obviously associated with spines or mounds. Spine bases and mounds comprise only 3 of 35%, respectively, of the outline of dendritic profiles, however, indicating that the high incidence of polyribosomes under these elements cannot be accounted for by chance. To attempt to determine whether the mounds represent the base of dendritic spines, 68 mounds in 21 dentritic profiles were selected from the middle of the series of 20 serial sections. Ninetine of these mounds (28%) were continuous with an identified spine, and an additional 31% were continuous with thin processes of the size and appearance of spine necks. Thus, most of the mounds probably do represent the base of spines which extend out of the plane of a single section.
Medial septal area lesions disrupt theta rhythm and cholinergic staining in medial entorhinal cortex and produce impaired radial arm maze behavior in rats
Authors: Mitchell SJ , Rawlins JN , Steward O , Olton DS
Published: March 2018

This study was designed to determine (1) which brain area paces the theta rhythm in the medial entorhinal cortex (MEC) of rats and (2) the extent to which the behavioral effects of lesions in the medial septal area (MSA), which disrupt the cholinesterase-related pathway to the hippocampal formation, resemble the effects previously reported to result from fimbria-fornix lesions. MSA lesions abolished or decreased theta rhythm in dorsal hippocampus (DHPC) and MEC; acetylcholinesterase (AChE) staining was depleted or diminished in all of the hippocampus and entorhinal cortex. Rats with MSA lesions were impaired on acquisition of a radial arm maze task. Unilateral fimbria lesions left theta rhythm and AChE staining essentially unaltered in ipsilateral DHPC and MEC but depleted AChE in ipsilateral ventral hippocampus (VHPC) and ventral lateral entorhinal cortex (LEC). A lesion of the dorsal fornix at the level of the hippocampal flexure left ipsilateral DHPC theta rhythm and AChE stain unaltered while causing a substantial reduction in theta rhythm and depletion of AChE in ipsilateral MEC. AChE staining was complete in VHPC and LEC. These results suggest tha MSA paces MEC theta rhythm and that the presumed cholinergic projection which mediates this function travels in the dorsal fornix. The fimbria carries a presumed cholinergic projection to ventral LEC. Rats with MSA lesions can learn a radial arm maze task, unlike rats with fimbria- fornix lesions, but they learn significantly slower than normal rats.
Neuronal firing in the inferotemporal cortex of the monkey in a visual memory task
Authors: Fuster JM , Jervey JP
Published: March 2018

The objective of this study was to elucidate the functional role of neurons in the inferotemporal cortex of the primate. Single unit activity was recorded with microelectrodes in monkeys performing a visual delayed matching-to-sample task. On each trial, the animal was exposed briefly to a color - the sample - and, after a period of delay, had to select the same color among two or four colors simultaneously presented. Thus, correct performance of the task required perception, retention, and recognition of the sample color for every trial. A large number of inferotemporal units were seen to react to the stimuli with changes of firing frequency. Many units showed color-dependent reactions, suggesting their involvement in perception and discrimination of colors. A substantial contingent of cells showed increased, sustained, and in some cases, color-dependent discharge during the delay which was not necessarily preceded or succeeded by firing changes in sample or match periods. It is proposed that those cells were engaged in temporary retention of the sample stimulus. Since most of the inferotemporal units examined showed firing changes in more than one period of a trial, they appeared to be involved in more than one of the operations required by the task. Thus, the data do not support a clear-cut topographic separation of visual functions within the inferotmeporal cortex. However, neurons that appear to participate in visual memory, either exclusively or in addition to other functions, are concentrated in the cortex of the lower banks of the superior temporal sulcus.
Dopamine deficiency in the weaver mutant mouse
Authors: Schmidt MJ , Sawyer BD , Perry KW , Fuller RW , Foreman MM , Ghetti B
Published: March 2018

The dopamine system in weaver mutant mice (B6CBA-Aw-J/A background) was studied. Dopamine was 27% lower in the olfactory tubercle, 77% lower in the frontal cortex, and 75% lower in the striatum of 6-month-old weaver mice compared to control mice of the same age. Norepinephrine and serotonin were not lower in these brain areas. Tyrosine hydroxylase activity in the striatum was measured with a radiometric assay and was 70% lower in weaver mice. Examination of mice from 11 to 180 days of age revealed that the dopamine system failed to develop in weaver mice. Motor activity in individual animals was assessed using circular photocell activity cages with minimal illumination. Apomorphine and pergolide, direct dopamine agonists, increased activity more in weaver mice than in normal littermates. Amphetamine, which releases endogenous stores of dopamine, was less active in mutant mice. These findings provide suggestive evidence that postsynaptic dopamine receptors in weaver mutants might have become supersensitive as a result of lower levels of dopamine in motor areas of the brain. Anatomical evidence of dopamine system abnormalities was found in weaver mice by examination of serial sections cut from the midbrain of mutant and normal mice. The pars compacta of the substantia nigra in weaver mice appeared hypocellular when compared with the corresponding sections from controls. Fewer large neurons were seen in the affected animals. This study illustrates that weaver mice have specific deficiencies in the dopamine system. The weaver mouse might provide a way of examining the biochemical and behavioral effects of long term dopamine deficiency and a way to examine drugs to treat dopamine-deficient states in vivo.
Dopamine action on hippocampal pyramidal cells
Authors: Benardo LS , Prince DA
Published: March 2018

Dopamine (DA) was applied to CA1 region pyramidal cells in slices of guinea pig hippocampus maintained in vitro in order to examine its electrophysiological effect on CNS neurons. DA induced hyperpolarization of membrane potential and an increased conductance in 75% the 21 CA1 neurons to which it was applied. DA also augmented the afterhyperpolarizations and increased conductance which normally follow spike trains in these neurons. These effects were not altered by intracellular injections of Cl- but were blocked when slices were bathed in Mn2+ solutions. The Mn2+ blockade of DA-induced hyperpolarizations could be overcome when large amounts of agonists were applied. The DA effects were long lasting, were mimicked by the dopamine agonists apomorphine and Epinine, and were blocked by the dopamine antagonists flupenthixol and chlorpromazine. Extracellular or intracellular application of cyclic AMP mimicked the effects of DA. The results suggest that DA-induced hyperpolarization and conductance changes are mediated by a Ca2+-activated K+ conductance. DA may increase the intracellular Ca2+ concentration through effects on one of the Ca2+ buffering mechanisms. The long duration of these effects suggest that DA works though some intracellular intermediary, perhaps cyclic AMP, considering that the actions of cyclic AMP on membrane properties are similar to those of DA. The dopaminergic projection to the hippocampus should have a powerful inhibitory action, which would be most effective in modulating the activities of neurons exhibiting high levels of excitability, particularly cells involved in cyclical burst generation.
Binding, internalization, and retrograde transport of 125I-nerve growth factor in cultured rat sympathetic neurons
Authors: Claude P , Hawrot E , Dunis DA , Campenot RB
Published: March 2018

Sympathetic neurons internalize nerve growth factor (NGF) and transport it retrogradely to their cell bodies where it appears to serve a trophic function in maintaining neuronal survival. We have characterized the binding, internalization, and retrograde transport of 125I-NGF by cultured rat sympathetic neurons. After 3 to 4 weeks in culture, sympathetic neurons possessed approximately 2 X 10(7) specific, cell surface NGF binding sites per neuron with an apparent affinity constant of 2 to 5 X 10(9) M. The density of binding sites on the plasma membrane of the neurites approximately twice that on the plasma membrane of the cell bodies. Because of the extensive network of neuronal processes, the neurites probably account for more than 99.5% of the total binding in mature cultures. Using electron microscope autoradiography, we localized the distribution of 125I-NGF in the cell body following a 1-hr exposure to 125I-NGF. The majority of silver grains were associated with lysosomal organelles, including secondary lysosomes, residual bodies, and multivesicular bodies (MVB). The MVB were the most heavily labeled, with a labeling density (L.D.) of 21, while the lysosomes had a L.D. of 3.1. To study the retrograde transport of 125I-NGF, neurons were grown in compartmentalized culture dishes and their distal processes were exposed to 125I-NGF. Radioactive material was transported to the cell bodies at the rate of approximately 3 mm/hr. The transport mechanism was sensitive to colchicine and was saturable with respect to NGF. After 8 hr of transport, when the radioactivity in the cell bodies had reached a steady state, the label again was localized primarily to the MVB (L.D. = 16.8) and the lysosomes (L.D. = 3.8). The nuclei were not labeled significantly and had an overall L.D. of 0.47. We saw no evidence for the accumulation of NGF by the nuclear membrane, the nucleolus, or chromatin.
Electrophysiology and morphology of the developing hippocampus of fetal rabbits
Authors: Schwartzkroin PA , Kunkel DD
Published: March 2018

The pyramidal neurons of fetal rabbit hippocampus were studied using intracellular electrophysiological techniques in in vitro slice preparations. Correlative light and electron microscopic analyses were carried out on hippocampus during the 21st through the 29th day of fetal gestation. In intracellular experiments, neurons with all-or-none action potentials and near-adult level resting potentials were found even in the youngest preparations. Synaptic activity, however, was rare until about 24 days of gestation. CA1 neurons showed primarily excitatory synaptic potentials during fetal development, whereas CA3 neurons displayed both inhibitory and excitatory postsynaptic potentials at early stages. Anatomical studies suggested that pyramidal cell precursors were still dividing and migrating at 21 days; by 29 days, cellular migration was completed, and cellular intercommunication in the form of synapses was increasing. These experiments demonstrate that fetal central nervous system (CNS) material can be studied electrophysiologically without growing tissue in culture. Our results suggest that the newly differentiated hippocampal neurons have a limited repertoire of activities. Such data may provide a link between in vivo studies of postnatal CNS development and cell and tissue culture investigations of the properties of immature neurons.
Changes in expression of glial antigens M1 and C1 after cerebellar injury
Authors: Lagenaur C , Masters C , Schachner M
Published: March 2018

In response to mechanical injury in the adult mouse cerebellum, Bergmann glia and astrocytes of the granular layer exhibit abnormally increased expression of M1 antigen, while expression of C1 antigen in Bergmann glia is reduced. these reciprocal changes in two different astrocytic antigenic determinants (each recognized by monoclonal antibodies) are easily detected in the immediate area of the wound 4 days after the lesion. Although loss of C1 antigen from Bergmann glia remains localized to the area of the wound, abnormal M1 expression becomes widespread in cerebellar astrocytes, also affecting the contralateral side of the injured cerebellum at its peak 8 to 12 days after injury. These findings suggest that previous observations of abnormal expression of the two antigens in the cerebellum of mutant mice (Sommer, I., and M. Schachner (1981) J. Supramol. Struct. 16: 53- 74) might be interpreted with the view that a glial reaction to pathological state might be induced by genetically programmed neuronal cell death and/or abnormal development. We therefore postulate that expression of M1 in astrocytes that normally do not express this antigen and repression of C1 in normally positive astrocytes are indicative of a distinct functional state of astroglia, reactive gliosis.
Impulse activity in presynaptic dendrites: analysis of mitral cells in the isolated turtle olfactory bulb
Authors: Mori K , Nowycky MC , Shepherd GM
Published: March 2018

Impulse activity has been reported in neuronal dendrites in several regions of the central nervous system, where it is believed to assist in boosting transmission of signals from remote dendritic sites to the cell body. We have studied this activity in the dendrites of mitral cells in an isolated preparation of the turtle olfactory bulb. Intracellular recordings have been obtained from mitral cells responding to single volleys in the olfactory nerves or lateral olfactory tract. In addition to the large somatic spike, a small fast prepotential (FPP) was present in nearly all cells in response to an orthodromic volley in the olfactory nerves, but it was never seen in antidromic responses from the lateral olfactory tract. Collision tests using antidromic and orthodromic volleys showed that the EPP does not propagate into the axon. Hyperpolarizing current injections caused delay and blocking of the soma spike with little effect on the FPP response. These and other tests provided evidence to localize the EPP in the dendrites and to distinguish it from injury potentials and from spikes in the axon hillock or axonal initial segment. These results suggest that one function of the impulse in mitral cell dendrites is the classical one of boosting transmission of synaptic responses from the glomerular tuft to the cell body. In addition, it si well established that mitral cell dendrites are presynaptic to the dendrites of interneurons within the bulb and that these connections provide pathways for recurrent inhibition of the mitral cells. It therefore appears that the dendritic impulse in mitral cells acts as a booster for local dendritic synaptic output. These results provide further evidence for the multiple state-dependent input-output functions of cells with presynaptic dendrites.
Cholinergic projections from the basal forebrain of rat to the amygdala
Authors: Nagai T , Kimura H , Maeda T , McGeer PL , Peng F , McGeer EG
Published: March 2018

Cholinergic afferents to the amygdala from the basal forebrain were studied using di-isopropyl fluorophosphate-AChE histochemistry in combination with retrograde tracing using various fluorescent dyes. Cells sending their axons to the amygdala and staining intensely for AChE were located mainly in the nucleus of the substantia innominata. They also were found in the ventral part of the globus pallidus, the horizontal limb of the nucleus tractus diagonalis Broca, and the nucleus interstitialis ansae lenticularis. A correspondence was established between these cells and cells staining for choline acetyltransferase by immunohistochemistry in both distribution and morphology. Non-cholinergic neurons which send their axons to the amygdala also were found in the substantia innominata complex.
Development of Thy-1 antigen on cerebellar neurons in culture
Authors: Fields KL , Currie DN , Dutton GR
Published: March 2018

The Thy-1.1 cell surface antigen was demonstrated by indirect immunofluorescence on two types of neurons in dissociated cell cultures of developing rat cerebellum. In cultures from postnatal rats, small cells predominated. They bound tetanus toxin, a neuronal marker, and did not have the capacity to take up gamma-aminobutyric acid (GABA) as measured by autoradiography. From these properties, we conclude that they are granule cells. These neurons began to express the surface antigen Thy-1.1 by 2 weeks in culture, and by 4 weeks, the antigen was detected on about 40% of all of the surviving neurons. The second type of neuron, which may be a heterogeneous mixture of cerebellar neurons, was numerous only in cultures prepared from embryonic rats. They were larger than granule cells and expressed Thy-1.1 antigen after a few days in culture. Such cells bound tetanus toxin and were negative for the glial markers galactocerebroside and glial fibrillary acidic protein. Thy-1-positive cells and cells with high GABA uptake were most frequent in embryonic day 19 cultures, where 40 to 50% of all of the neurons were positive for either property. They survived about 1 week in culture. The size and frequency of Thy-1 cells and the frequency of similar cells with high GABA uptake suggest that the embryonic rat cultures included many Purkinje cells, which express Thy-1.
The binding of kappa- and sigma-opiates in rat brain
Authors: Wolozin BL , Nishimura S , Pasternak GW
Published: March 2018

Detailed displacements of [3H]dihydromorphine by ketocyclazocine and SKF 10,047, [3H]ethylketocyclazocine by SKF 10,047, and [3H]SKF 10,047 by ketocyclazocine are all multiphasic, suggesting multiple binding sites. After treating brain tissue in vitro with naloxazone, all displacements lose the initial inhibition of 3H-ligand binding by low concentrations of unlabeled drugs. Together with Scatchard analysis of saturation experiments, these studies suggest a common site which binds mu-, kappa, and sigma-opiates and enkephalins equally well and with highest affinity (KD less than 1 nM). The ability of unlabeled drugs to displace the low affinity binding of [3H]dihydromorphine (KD = 3 nM), [3H]ethylketocyclazocine (KD = 4 nM), [3H]SKF 10,047 (KD = 6 nM), and D- Ala2-D-Leu5-[3H]enkephalin (KD = 5 nM) remaining after treating tissue with naloxazone demonstrates unique pharmacological profiles for each. These results suggest the existence of distinct binding sites for kappa- and sigma-opiates which differ from those sites which selectively bind morphine (mu) and enkephalin (delta).
A comparative study of avermectin B1a and other modulators of the gamma- aminobutyric acid receptor . chloride ion channel complex
Authors: Pong SS , DeHaven R , Wang CC
Published: March 2018

The interactions of the anthelmintic agent avermectin B1a, the anticonvulsant pentobarbital, and the anxiolytic tracazolate with the gamma-aminobutyric acid (GABA) receptor . chloride ion channel complex in rat brain membrane were studied. The results indicated that they all potentiated ligand binding to the GABA and benzodiazepine receptors. The stimulatory effects of avermectin B1a and pentobarbital, but not tracazolate, on GABA receptor binding were inhibited by picrotoxin. The effect of avermectin B1a was not additive with those of tracazolate and pentobarbital. On the other hand, the stimulatory effect of GABA on benzodiazepine binding was additive with those of avermectin B1a and pentobarbital, but tracazolate and pentobarbital inhibited the effect of avermectin B1a. In the receptor heat inactivation experiments, avermectin B1a and clonazepam protected GABA receptors, whereas avermectin B1a and GABA protected benzodiazepine receptors. Tracazolate, pentobarbital, and picrotoxin did not protect either receptor. These findings suggest that the recognition sites for the benzodiazepines, avermectin B1a, pentobarbital, and picrotoxin are coupled allosterically to the GABA receptor . chloride ion channel complex in different ways. The binding sites for avermectin B1a may be partially shared by picrotoxin, pentobarbital, and tracazolate.
Morphology and distribution of retinal ganglion cells projecting to different layers of the dorsal lateral geniculate nucleus in normal and Siamese cats
Authors: Leventhal AG
Published: March 2018

Electrophoretic injections of horseradish peroxidase were made into physiologically characterized sites within the different layers of the dorsal lateral geniculate nuclei (LGNd) of normal and Siamese cats. The histochemical procedures used stained the cell bodies, dendrites, and axons of retrogradely labeled ganglion cells. In both normal and Siamese cats, only alpha and beta ganglion cells are labeled by injections restricted to the A laminae. In normal cats, the alpha/beta ratios (number of labeled alpha cells/number of labeled alpha + beta cells) resulting from injections into lamina A increase from about 0.045 at 0.5 mm from the area centralis to about 0.12 in the far periphery. The alpha/beta ratios observed outside of the area centralis in normal cats following injections into different parts of lamina A1 were lower at each eccentricity than those resulting from injections into corresponding parts of lamina A. Also, the cell bodies and dendritic fields of alpha and beta cells projecting to lamina A1 are somewhat larger than those projecting to corresponding parts of lamina A. Outside of the area centralis, the relative numbers of alpha and beta cells projecting to Siamese lamina A are normal. However, alpha cells comprise an abnormally small proportion of ganglion cells projecting to the normal segments of Siamese lamina A1 and an abnormally large proportion of cells projecting to the abnormal segments of lamina A1. In Siamese cats, alpha and beta cells projecting to lamina A1 are distributed continuously throughout virtually all of the ipsilateral and contralateral temporal retinas. Since large parts of the ipsilateral and contralateral hemifields are not represented in Siamese lamina A1, it seems that some of the retinal afferents to this lamina are being suppressed. Injections into the C laminae of the LGNd show that the same morphological classes of ganglion cells project to these laminae in normal and Siamese cats. The classes projecting to the contralateral as C laminae (laminae C and C2) include alpha, beta, gamma, and epsilon as well as two other groups of cells referred to g1 and g2 cells, gamma, epsilon, g1, and g2 cells project to the ipsilateral C lamina (lamina C1). In siamese, but not in normal cats, examples of all of these types are found far into the contralateral temporal retina following injections involving lamina C1. This indicates that all classes projecting to the ipsilateral C lamina misproject in Siamese cats.
Subfornical organ-median preoptic connections and drinking and pressor responses to angiotensin II
Authors: Lind RW , Johnson AK
Published: March 2018

The subfornical organ (SFO) and the periventricular tissue of the anteroventral third ventricle (AV3V) have been shown to be important for the central action of circulating angiotensin. Recent anatomical findings have elucidated neural connections between the SFO and several structures within the AV3V region. The present study examined the function of fibers between the SFO and the median preoptic nucleus. Horizontal knife cuts rostral to the anterior commissure severed precommissural fibers between the SFO and the median preoptic nucleus. Cuts immediately dorsal to the anterior commissure interrupted both pre- and postcommissural connections. Rats with cuts of both sets of fibers evidenced a virtual absence of drinking responses following subcutaneous injections of angiotensin, while rats with selective cuts of precommissural fibers manifested a partial, but significant, reduction in responding. The two groups of animals showed similar attenuations in drinking responses following subcutaneous injections of hypertonic saline. Rats with cuts of both pre- and postcommissural fibers evidenced an attenuation of drinking responses elicited by centrally administered angiotensin. Pressor responses following intravenous and intraventricular angiotensin injections were not reduced specifically by the experimental knife cuts. These findings are consistent with a model that postulates that angiotensin receptors, and perhaps osmoreceptors, in the SFO send excitatory neural information to the median preoptic nucleus for the mobilization of thirst.