bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of cell and fiber vulnerability in the mesostriatal system of the mutant mouse weaver. I. Gradients and compartments
Authors: Graybiel AM , Ohta K , Roffler-Tarlov S
Published: March 2018

In mice carrying the autosomal recessive gene weaver, there is a massive postnatal loss of dopamine in the caudoputamen, the target of the nigrostriatal system, with relative (though not complete) preservation of dopamine in the ventral striatum, a target of the mesolimbic system. There is concomitant death of catecholaminergic neurons in the substantia nigra, with much less cell death in the limbic midbrain area. In the study reported here, we have reexamined the mesostriatal system of weaver mice by means of tyrosine hydroxylase (TH) immunohistochemistry in order to determine the local architecture of the defect within the striatum and substantia nigra. For the dorsal striatum, the most striking finding was the appearance in the weaver caudoputamen of small pockets of especially weak immunostaining within a larger dorsal zone of generally reduced TH-positive neuropil. These pockets were identified as striosomes by calbindin28k and met- enkephalin immunohistochemistry carried out on adjacent sections. In dorsal, central, and caudal sectors of the caudoputamen, there was also more generalized depletion of TH-immunoreactive neuropil. In the mid- brains of the mutants, the patterns of loss of TH-positive neurons appeared to correspond to these distributions of reduced immunostaining in the striatum. In the substantia nigra pars compacta, ventrally situated TH-positive neurons were especially affected, suggesting preferential depletion of TH-positive neurons projecting to striosomes. In addition, there was a central sector of nearly complete loss of TH- positive neurons in the substantia nigra para compacta and a marked depletion of TH-positive neurons in cell group A8 that, together, may have accounted for the diminution of TH-positive innervation of the striatal matrix. We conclude that the effects of the weaver gene discriminate among mesostriatal subsystems not only according to the regional affiliations of these subsystems within the dorsal and ventral striatum, but also according to the preferential association of the subsystems for the striosomal and matrical compartments of the caudoputamen. The depletion of TH-positive innervation was not confined to the dorsal striatum proper. The defect extended into the adjoining nucleus accumbens, where it appeared to affect the lateral “core” division, and included also a lateral part of the olfactory tubercle. Thus, as in the dorsal striatum, the defect in the TH-positive innervation of the ventral striatum closely follows the local architecture of this striatal region. Neuronal loss in the ventral tegmental area was not evident on qualitative analysis, but at the border between lateral cell group A 10 and medial cell group A9 there was obvious loss of immunostained neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
Electrophysiological properties of neuroendocrine cells of the intact rat pars intermedia: multiple calcium currents
Authors: Williams PJ , MacVicar BA , Pittman QJ
Published: March 2018

Intracellular recordings for current and voltage clamping were obtained from 130 neuroendocrine cells of the pars intermedia (PI) in intact pituitaries maintained in vitro. Spontaneous and evoked action potentials were blocked by TTX or by intracellular injection of a local anesthetic, QX-222. After potassium (K+) currents were blocked by tetraethylammonium (TEA), 4-aminopyridine, and intracellular cesium (Cs+), 2 distinct calcium (Ca2+) spikes were observed which were differentiated by characteristic thresholds, durations, and amplitudes. Both Ca2+ spikes were blocked by cobalt (Co2+) but were unaffected by TTX or QX-222. The low-threshold spike (LTS) had a smaller amplitude and inactivated when membrane potential was depolarized past -40 mV or when evoked at a fast rate (greater than 0.5 Hz). The high-threshold spike (HTS) typically had a larger amplitude and longer duration, was not inactivated at potentials which inactivated the LTS, and could be evoked at rates of up to 10 Hz. Single-electrode voltage-clamp analysis revealed that 3 distinct components of the Ca2+ current were present in most cells. From a negative holding potential (-90 mV), 2 separate peak inward currents were observed; a low-threshold transient current, similar to a T-type Ca2+ current, activated at -40 mV, whereas a large- amplitude inactivating current activated above -20 mV. This large inactivating Ca2+ current was significantly inactivated at a holding potential of -40 mV or by brief prepulses to positive potentials, and was similar to an N-type Ca2+ current. A sustained Ca2+ current (L- type) was observed which was not altered by different holding potentials.(ABSTRACT TRUNCATED AT 250 WORDS)
Synaptic modulation by dopamine of calcium currents in rat pars intermedia
Authors: Williams PJ , MacVicar BA , Pittman QJ
Published: March 2018

Melanotrophs of the rat pars intermedia are innervated by dopaminergic fibers traveling through the pituitary stalk which inhibit secretion via an action on D-2 receptors. As secretion from the melanotroph has been shown to be calcium (Ca2+) dependent, it is possible that dopamine may have an action to inhibit Ca2+ currents in these cells. This possibility was tested by examining the effects of exogenously applied dopaminergic agonists or synaptically released dopamine upon Ca2+ currents recorded under single electrode voltage clamp in intact rat pars intermedia in vitro. Following blockade of sodium and potassium currents in melanotrophs, Ca2+ spikes were elicited with intracellular injection of depolarizing currents; electrical stimulation of the pituitary stalk caused an inhibition of the Ca2(+)-based action potentials which lasted for several seconds. Using single-electrode voltage-clamp techniques, we recorded inward Ca2+ currents corresponding to the T, N, and L types (see Williams et al., 1990). Stimulation of the pituitary stalk inhibited both the low- and high- threshold peak inward Ca2+ currents elicited from a holding potential of -90 mV. In contrast, when noninactivating Ca2+ currents were elicited from a holding potential of -30 mV, the currents were not altered by stalk stimulation. This pattern of inhibition of the Ca2+ currents was consistent with the preferential inhibition, by stalk stimulation, of the N and T Ca2+ currents, while sparing the L current. We observed that inhibition of Ca2+ currents due to stalk stimulation was completely reversed by bath perfusion of domperidone (1 microM), an antagonist of dopamine at the D-2 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Differential expression of two neuronal intermediate-filament proteins, peripherin and the low-molecular-mass neurofilament protein (NF-L), during the development of the rat
Authors: Escurat M , Djabali K , Gumpel M , Gros F , Portier MM
Published: March 2018

The expression of peripherin, an intermediate filament protein, had been shown by biochemical methods to be localized in the neurons of the PNS. Using immunohistochemical methods, we analyzed this expression more extensively during the development of the rat and compared it with that of the low-molecular-mass neurofilament protein (NF-L), which is expressed in every neuron of the CNS and PNS. The immunoreactivity of NF-L is first apparent at the 25-somite stage (about 11 d) in the ventral horn of the spinal medulla and in the posterior part of the rhombencephalon. The immunoreactivity of peripherin appears subsequently, first colocalized with that of NF-L. Both immunoreactivities then spread out along rostral and caudal directions, but whereas the immunoreactivity of NF-L finally becomes noticeable in every part of the nervous system, that of peripherin remains localized to (1) the motoneurons of the ventral horn of the spinal medulla; (2) the autonomic ganglionic and preganglionic neurons; and (3) the sensory neurons. These results demonstrate that, in the neurons that originate from migrating neural crest cells, the immunoreactivities of peripherin and of NF-L become apparent only when they have reached their destination. The results also show that peripherin is expressed more widely than has been previously observed and that this protein occurs in neuronal populations from different lineages (neural tube, neural crest, placodes) with different functions (motoneurons, sensory and autonomic neurons). The common point of these neurons is that they all have axons lying, at least partly, at the outside of the axis constituted by the encephalon and the spinal medulla; this suggests that peripherin might play a role in the recognition of the axonal pathway through the intermediary of membrane proteins.
Three-dimensional autoradiographic localization of quench-corrected glycine receptor specific activity in the mouse brain using 3H- strychnine as the ligand
Authors: White WF , O'Gorman S , Roe AW
Published: March 2018

The autoradiographic analysis of neurotransmitter receptor distribution is a powerful technique that provides extensive information on the localization of neurotransmitter systems. Computer methodologies are described for the analysis of autoradiographic material which include quench correction, 3-dimensional display, and quantification based on anatomical boundaries determined from the tissue sections. These methodologies are applied to the problem of the distribution of glycine receptors measured by 3H-strychnine binding in the mouse CNS. The most distinctive feature of this distribution is its marked caudorostral gradient. The highest densities of binding sites within this gradient were seen in somatic motor and sensory areas; high densities of binding were seen in branchial efferent and special sensory areas. Moderate levels were seen in nuclei related to visceral function. Densities within the reticular formation paralleled the overall gradient with high to moderate levels of binding. The colliculi had low and the diencephalon had very low levels of binding. No binding was seen in the cerebellum or the telencephalon with the exception of the amygdala, which had very low levels of specific binding. This distribution of glycine receptors correlates well with the known functional distribution of glycine synaptic function. These data are illustrated in 3 dimensions and discussed in terms of the significance of the analysis techniques on this type of data as well as the functional significance of the distribution of glycine receptors.
Light and electron microscopic localization of beta I-, beta II-, and gamma-subspecies of protein kinase C in rat cerebral neocortex
Authors: Tsujino T , Kose A , Saito N , Tanaka C
Published: March 2018

We have localized the beta I-, beta II-, and gamma-subspecies of protein kinase C in cerebral neocortex with light and electron microscopic immunocytochemistry using a monoclonal antibody against gamma-PKC and polyclonal antisera to beta I- or beta II-PKC-specific oligopeptides. The gamma-PKC-immunopositive cell bodies were seen mostly in layers II, V, and VI, and the vast majority of them were pyramidal cells. The beta II-PKC immunoreactive cell bodies were observed in layers II, III, V, and VI, and most of them seemed to be pyramidal cells. Both gamma- and beta II-PKC were colocalized in some pyramidal cells in layers II, V, and VI. The small number of beta I-PKC immunoreactive cell bodies were observed in the neocortex, and many of them were nonpyramidal cells. About 80% of the beta I-PKC- immunoreactive cells were shown to be GABAergic neurons. The gamma-PKC- immunopositive neuropils were observed in layers I, II, V, and VI, while beta II-PKC-immunoreactive neuropils were seen in layers I-III, V, and VI. The distribution of each subspecies is much the same throughout all regions of the neocortex, although with different intensities of immunoreactivity. electron microscopic studies revealed that, in the perikarya, gamma-PKC was distributed throughout the cytoplasm, beta I-PKC was just adjacent to the plasma membrane, and beta II-PKC was located around the Golgi complex. The immunoreactivity of these 3 subspecies was also seen in dendrites and axons, but no immunoreactivity of these subspecies was found in the presynaptic terminals in the present study. The discrete cellular and intracellular distributions of protein kinase C subspecies imply that each subspecies has a specific role in neuronal activity in the cerebral neocortex.
In vivo visualization of the growth of pre- and postsynaptic elements of neuromuscular junctions in the mouse
Authors: Balice-Gordon RJ , Lichtman JW
Published: March 2018

In order to study how neuromuscular junctions grow, we have repeatedly viewed the same junctions in mouse sternomastoid muscles at monthly intervals from 2 weeks to 18 months of age. Motor nerve terminals were stained with the nontoxic fluorescent dye 4-Di-2-ASP (Magrassi et al., 1987), and postsynaptic ACh receptors were labeled with fluorescently tagged alpha-bungarotoxin. Neuromuscular junctions grew primarily by expansion of existing motor nerve terminal and postsynaptic receptor regions without the addition or loss of synaptic areas. The expansion of pre- and postsynaptic specializations was precisely matched, suggesting that as neuromuscular junctions grow, the opposing specializations enlarge simultaneously. Each neuromuscular junction grew in length and width at the same rate that muscle fibers enlarged in those 2 dimensions, suggesting that junctional growth might be a mechanical consequence of muscle fiber growth. Repeated visualization of ACh receptors over time showed that previously labeled receptors spread apart in the membrane occupying a progressively larger area as muscle fibers grew. At the same time, new receptors were intercalated throughout the enlarged postsynaptic area. Thus, the growth of postsynaptic regions appears to be directly related to the expansion of the muscle fiber membrane as muscle fibers grow. The maintained alignment between growing motor nerve terminals and postsynaptic regions suggests that nerve terminal growth may be a consequence of its adhesion to growing postsynaptic specializations. This conclusion is supported by the coextensive stretching of motor nerve terminals and postsynaptic regions when muscle fibers are stretched. Thus, the growth of motor nerve terminals is coupled to the growth of postsynaptic regions, and the growth of the postsynaptic regions is in turn coupled to the growth of muscle fibers. In this way, the branching pattern of neuromuscular junctions may be stably maintained despite ongoing enlargement of synaptic area.
T-type calcium channels: heterogeneous expression in rat sensory neurons and selective modulation by phorbol esters
Authors: Schroeder JE , Fischbach PS , McCleskey EW
Published: March 2018

We report selective inhibition of low-threshold, T-type calcium channels by a phorbol ester in rat sensory neurons. Cells were exposed, either acutely or with 15–60 min preincubations, to low concentrations of phorbol 12-myristate 13-acetate, (PMA), an activator of protein kinase C; if the temperature was 29 degrees C or higher, T-type Ca current was diminished without effect on high-threshold Ca current. In untreated cells, the amplitude of T-type Ca current varies widely among neighboring sensory neurons. T channels are absent in about 25% of cells, provide a small current near threshold for the majority of cells, and are a dominant pathway for calcium entry in a small subset of neurons. The results are of interest because, by selectively inhibiting a calcium channel expressed differently among subpopulations of sensory neurons, activation of protein kinase C might selectively suppress particular sensations.
Topographic organization of neurons in the acoustic thalamus that project to the amygdala
Authors: LeDoux JE , Farb C , Ruggiero DA
Published: March 2018

Projections from the posterior thalamus to the amygdala have been implicated in the processing of the emotional significance of acoustic stimuli. The aim of the present studies was to determine which areas of the amygdala receive afferents from posterior thalamic structures that, in turn, receive afferents (presumably acoustic afferents) from the inferior colliculus. Projections from the posterior thalamus to the amygdala and striatum were examined in rats using anterograde and retrograde axonal transport techniques. Following injections of WGA-HRP into the posterior thalamic areas [including the medial division of the medial geniculate body, the posterior intralaminar nucleus (PIN) and the medial posterior complex (POM)], anterograde transport was seen in the lateral (AL), central (ACE), medial (AM), and basomedial (ABM) nuclei of the amygdala and in the amygdalostriatal transition area (AST) and posterior caudate putamen (CPU). Injection of WGA-HRP into each anterogradely labeled area produced retrograde transport to the posterior thalamus, but the pattern of transport varied with the site of the injection. Injections in AL and AST produced retrograde transport to neurons in the medial division of the medial geniculate body (MGM), PIN, suprageniculate nucleus (SG) and, to a lesser extent, the lateral posterior nucleus (LP). Injections of the ACE, AM, and ABM, in contrast, only labeled cells in POM. While the MGM, PIN, and SG each receive afferents from the inferior colliculus, POM does not. AL and AST, therefore, receive inputs from thalamic areas that, in turn, receive inputs from the inferior colliculus.
Autoradiographical detection of cholecystokinin-A receptors in primate brain using 125I-Bolton Hunter CCK-8 and 3H-MK-329
Authors: Hill DR , Shaw TM , Graham W , Woodruff GN
Published: March 2018

In vitro autoradiography was performed in order to visualize cholecystokinin-A (CCK-A) receptors in sections of Cynomolgus monkey brain. CCK-A receptors were defined as those which displayed high affinity for the selective non-peptide antagonist MK-329 (L-364,718) and were detected in several regions by selective inhibition of 125I- Bolton Hunter CCK using MK-329 or direct labeling with 3H-MK-329. In the caudal medulla, high densities of CCK-A sites were present in the nucleus tractus solitarius, especially the caudal and medial aspects, and also the dorsal motor nucleus of the vagus. CCK-A sites were localized to a number of hypothalamic nuclei such as the supraoptic and paraventricular nuclei, the dorsomedial and infundibular nuclei as well as the neurohypophysis. The mammillary bodies and supramammillary nuclei also contained CCK-A receptor sites. High concentrations of CCK- A receptors were present in the substantia nigra zona compacta and also the ventral tegmental area and may be associated with dopamine cell bodies. Binding of 3H-MK-329 was also detected in parts of the caudate nucleus and ventral putamen. The detection, by autoradiographical means, of CCK-A receptors throughout the Cynomolgus monkey brain contrasts with similar studies performed using rodents and suggests differences in the density and, perhaps, the importance of CCK-A receptors in the primate as opposed to the rodent. The data suggest the possibility that CCK-A receptors may be involved in a number of important brain functions as diverse as the processing of sensory information from the gut, the regulation of hormone secretion, and the activity of dopamine cell activity.
Intrinsic and extrinsic factors influencing properties and growth patterns of identified leech neurons in culture
Authors: Acklin SE , Nicholls JG
Published: March 2018

An analysis has been made of intrinsic mechanisms influencing growth patterns of 2 identified leech interneurons in tissue culture. These small cells (known as DL and VL) display unusual arborizations in the ganglion. The distinctive branching patterns resemble the letter “T” for VL and the letter “Y” for DL. DL and VL cells contain serotonin and can be identified in situ with Neutral red. 1. DL and VL cells were isolated and cultured on 2 homogeneous substrates, concanavalin A (Con A) and leech extracellular matrix extract (ECM). Individual DL and VL cells in culture retained their ability to fire in spontaneous, rhythmical bursts. The synaptic connections formed in culture were specific and differed from those made by other serotonergic neurons. 2. On both Con A and ECM the neurons sprouted to reproduce their characteristic patterns. Every DL or VL cell that grew processes on ECM developed the appropriate Y- or T-shaped pattern. On Con A, most but not all of the cells showed specific Y or T patterns. The probability of sprouting was higher on Con A than on ECM. 3. Disruption of microtubular assemblies in freshly isolated DL and VL cells by treatment with nocodazole did not affect the later outgrowth of specific patterns in culture. 4. These results provide evidence that adult DL and VL leech neurons retain intrinsic information for determining a variety of their properties in culture: In particular, they reproduce type-specific neuritic patterns in the absence of extrinsic guidance cues. Moreover, the intrinsic pattern determining mechanism is not lost after the destruction of microtubular arrays within the cytoskeleton.
Eye position effects on visual, memory, and saccade-related activity in areas LIP and 7a of macaque
Authors: Andersen RA , Bracewell RM , Barash S , Gnadt JW , Fogassi L
Published: March 2018

We studied the effect of eye position on the light-sensitive, memory, and saccade-related activities of neurons of the lateral intraparietal area and area 7a in the posterior parietal cortex of rhesus monkeys. A majority of the cells showed significant effects of eye position, for each of the 3 types of response. The direction tuning of the light- sensitive, memory and saccade responses did not change with eye position but the magnitude of the response did. Since previous work showed a similar effect for the light-sensitive response of area 7a neurons (Andersen and Mountcastle, 1983; Andersen et al., 1985b), the present results indicate that this modulating effect of eye position may be a general one, as it is found in 3 types of responses in 2 cortical areas. Gain fields were mapped by measuring the effect of eye position on the magnitude of the response at 9 different eye positions for each neuron. The gain fields were usually planar or largely planar for all 3 types of response in both areas, indicating that the magnitude of the response usually varies linearly with both horizontal and vertical eye position. A similar observation was made previously for the gain fields of the light-sensitive response of area 7a neurons (Andersen et al., 1985b). Although gain fields sloped in all directions for the population of cells, the gain field slopes of the light- sensitive, memory and saccade responses for individual cells were usually similar. It is proposed that these eye position effects play an important role in making coordinate transformations for visually guided movement.
Descending control of electroreception. I. Properties of nucleus praeeminentialis neurons projecting indirectly to the electrosensory lateral line lobe
Authors: Bastian J , Bratton B
Published: March 2018

The first-order CNS processing region within the electrosensory system, the electrosensory lateral line lobe, receives massive descending inputs from the nucleus praeeminentialis as well as the primary afferent projection. The n. praeeminentialis receives its input from the electrosensory lateral line lobe as well as from higher centers; hence this nucleus occupies an important position in a feedback loop within the electrosensory system. This report describes the physiological properties of a category of n. praeeminentialis neurons characterized by very high spontaneous firing frequency, but relatively poor sensitivity to electrolocation targets as compared to neurons in the electrosensory lateral line lobe. These neurons are specialized to encode long-term changes in electric organ discharge amplitude with high resolution. Intracellular recording and Lucifer yellow staining of these neurons show that they are the previously described multipolar neurons of the n. praeeminentialis, and they project bilaterally to the posterior eminentia granularis. Posterior eminentia granularis efferents project to the electrosensory lateral line lobe forming its dorsal molecular layer. Hence, these multipolar cells influence the electrosensory lateral line lobe circuitry indirectly. The information that the multipolar cells encode regarding the electric organ discharge amplitude may be needed for a gain control mechanism operative within the electrosensory lateral line lobe. Previous studies have shown that the indirect projection from the n. praeeminentialis to the electrosensory lateral line lobe must be intact for this gain control mechanism to operate.
Descending control of electroreception. II. Properties of nucleus praeeminentialis neurons projecting directly to the electrosensory lateral line lobe
Authors: Bratton B , Bastian J
Published: March 2018

The nucleus praeeminentialis projects to the electrosensory lateral line lobe via 2 distinct pathways. Neurons that project to the posterior eminentia granularis and therefore influence the electrosensory lateral line lobe indirectly are described in the preceding report. This report describes the physiological properties and anatomical characteristics, revealed with Lucifer yellow staining, of n. praeeminentialis neurons that project directly to the ventral molecular layer of the electrosensory lateral line lobe. The neurons studied were the stellate cells described by Sas and Maler (1983), and we found 2 physiological subtypes of these. These neurons typically had no spontaneous activity, but responded vigorously to either increased electric organ discharge amplitude on the contralateral side of the body (ST-E cells) or to decreased amplitude (ST-I cells). These neurons also responded to low-frequency sinusoidal electric organ discharge amplitude modulations (AM) but were inhibited by AMs having frequencies greater than about 16 Hz. These stellate neurons were unable to encode information about long-term changes in electric organ discharge amplitude, but they responded very well to moving electrolocation targets. The relatively long response latency of these neurons suggests that they receive inputs from higher centers in addition to those from the electrosensory lateral line lobe. It is suggested that these cells alter the sensitivity of restricted populations of output cells in the electrosensory lateral line lobe and process temporally and spatially restricted stimuli. They may act to increase the intensity of the neural representation of important stimuli.
Learning and memory is reflected in the responses of reinforcement- related neurons in the primate basal forebrain
Authors: Wilson FA , Rolls ET
Published: March 2018

Certain basal forebrain neurons encode the learned reinforcement value of objects: they respond differentially to visual stimuli that signal availability of fruit juice (positively reinforcing) or saline (negatively reinforcing) obtained by lick responses in visual discrimination tasks. In this report we describe the rapid, learning- related changes in the responses of these neurons during the acquisition and reversal of the reinforcement contingency of a visual discrimination reversal task. The same neurons also responded differentially to novel and familiar stimuli in 2 recognition memory tasks, in which monkeys applied the learned rule that lick responses to novel stimuli elicited saline and responses to familiar stimuli elicited juice. These differential responses to novel and familiar stimuli thus reflected the reinforcement value of the stimuli. A single presentation of a novel or a familiar stimulus was sufficient to elicit a differential response which was maintained even when the stimulus had not been seen recently. The maintenance of the differential response indicates that these neurons are influenced by a durable memory for the stimuli, estimated to be 30 trials on average. These differential neurons were recorded in the substantia innominata, the diagonal band of Broca, and a periventricular region of the basal forebrain. The responses of the reinforcement-related neurons in these 3 regions were similar in most respects. These results support the conclusion that basal forebrain neurons respond to sensory stimuli that, through learning of different contingencies, signal the availability of reinforcement. We suggest that the properties of learning and memory reflected in these neuronal responses are due to afferent pathways from ventromedial regions of the prefrontal and temporal cortices and the amygdala, and that the responses of these neurons provide an enabling mechanism that facilitates the operation of diverse cortical regions in which specific sensory, motor, or mnemonic functions take place.
Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood
Authors: Gould E , Woolley CS , Frankfurt M , McEwen BS
Published: March 2018

Gonadal steroids are known to influence hippocampal physiology in adulthood. It is presently unknown whether gonadal steroids influence the morphology of hippocampal neurons in the adult intact rat brain. In order to determine whether female sex hormones influence hippocampal morphology in the intact adult, we performed Golgi impregnation on brains from ovariectomized rats and ovariectomized rats which received estradiol or estradiol and progesterone replacement. Removal of circulating gonadal steroids by ovariectomy of adult female rats resulted in a profound decrease in dendritic spine density in CA1 pyramidal cells of the hippocampus. Estradiol replacement prevented the observed decrease in dendritic spine density; progesterone augmented the effect of estradiol within a short time period (5 hr). Ovariectomy or gonadal steroid replacement did not affect spine density of CA3 pyramidal cells or granule cells of the dentate gyrus. These results demonstrate that gonadal steroids are necessary for the maintenance of normal adult CA1 hippocampal pyramidal cell structure. The short time course required to observe these effects (3 d for the estradiol effect and 5 hr for the progesterone effect) implies that CA1 pyramidal cell dendritic spine density may fluctuate during the normal (4–5 d) rat estrous cycle.
Differential effects of C- and N-terminal substance P metabolites on the release of amino acid neurotransmitters from the spinal cord: potential role in nociception
Authors: Skilling SR , Smullin DH , Larson AA
Published: March 2018

Extensive evidence implicates Substance P [SP(1–11)] as a primary afferent neurotransmitter or modulator of nociceptive information, and there is increasing evidence that the excitatory amino acids aspartate (Asp) and glutamate (Glu) may also act as nociceptive neurotransmitters. We have previously demonstrated that nociceptive stimulation (metatarsal injection of formalin) caused a tetrodotoxin (TTX)-sensitive release of Asp and a TTX-insensitive release of Glu from the dorsal spinal cord. We have also shown release of Asp and Glu following the direct infusion of SP(1–11), suggesting that formalin- induced Asp or Glu changes could be secondary to an initial release of SP(1–11). In contrast to nociception, pretreatment with TTX, reported here, had no effect on the SP(1–11)-induced release of Asp, suggesting a presynaptic mechanism. Behavioral experiments, in both our laboratory, and others, now suggest that the N-terminal products of SP metabolism play a distinct role in the modulation of SP(1–11) nociception, possibly through an interaction with an opiate receptor. To test the hypothesis that N- and C-terminal fragments of SP produce opposite effects on biochemical events potentially involved in nociception, we compared the effects of infusion of the N-terminal metabolite SP(1–7) and the C-terminal metabolite SP(5–11) on changes in the ECF concentration of amino acids in the spinal cord as a measure of their apparent release, using microdialysis. Intradiaylsate infusion of SP(5–11) increased the release of Asp, Glu, asparagine (Asn), glycine (Gly), and taurine (Tau). The changes in Asp, Glu, and Tau were similar in direction and magnitude to changes produced by SP(1–11) or formalin injection, further supporting the hypothesis that the C-terminal is responsible for the nociceptive effects of SP(1–11). In contrast, infusion of SP(1–7) significantly decreased the release of Asn, Tau, Glu, and Gly. This inhibition of amino acid release is consistent with the hypothesis that N-terminal metabolites produce opposite effects to those of C-terminal metabolites of SP(1–11). The decreases in Glu, Asn, Gly, and Tau following SP(1–7) infusion were significantly reduced by i.p. or intradialysate naloxone. Systemic naloxone had no significant effects on the SP(5–11)-induced amino acid changes; however, it did inhibit the SP(1–11)-induced increase in Asp and Glu. Intradialysate naloxone had no effect on the SP(1–11)-induced increases.(ABSTRACT TRUNCATED AT 400 WORDS)
Regulation of cytochrome oxidase protein levels by functional activity in the macaque monkey visual system
Authors: Hevner RF , Wong-Riley MT
Published: March 2018

The activity of cytochrome oxidase (CO), a mitochondrial enzyme of oxidative energy metabolism, is regulated by nerve cell functional activity. The mechanism of CO activity regulation was studied using histochemical and immunohistochemical methods to show the distributions of CO activity and protein, respectively, in the macaque monkey visual system under normal and experimental conditions. In normal animals, patterns of CO activity were found to reflect underlying patterns of CO protein distribution; for example, puffs of high CO activity in cortical area 17 contained high levels of CO protein. Experimental animals were injected monocularly with TTX for 3–4 weeks; this treatment blocks retinal impulses in the injected eye and results in decreased CO activity in lateral geniculate laminae and striate cortical columns normally driven by the treated eye. The experimentally induced decreases in CO activity were also found to reflect underlying parallel decreases in CO protein levels. These results suggest that CO activity is regulated mainly at the level of the local amount rather than the turnover number of the enzyme and imply that the rates of CO synthesis and/or degradation are regulated by neural functional activity.
Delayed, frequency-specific inhibition in the cochlear nuclei of mice: a mechanism for monaural echo suppression
Authors: Wickesberg RE , Oertel D
Published: March 2018

To understand how auditory information is processed in the cochlear nuclei, it is crucial to know what circuitry exists and how it functions. Previous anatomical experiments have shown that neurons in the deep layer of the dorsal cochlear nucleus (DCN) project topographically to the anteroventral cochlear nucleus (AVCN) (Wickesberg and Oertel, 1988). Because interneurons in the DCN and their targets in AVCN are excited by the same group of auditory nerve fibers, the projection is frequency-specific. Here we report that microinjections of glutamate in the DCN evoke trains of IPSPs in individual, impaled AVCN neurons in brain slices of the cochlear nuclear complex. Only injections along a rostrocaudal band in the DCN, matching the anatomical projection of tuberculoventral neurons, evoke IPSPs; elsewhere, there were no responses to the glutamate. The inhibition is blocked by 0.5 microM strychnine. Both bushy and stellate cells are targets of the inhibitory projection. Inhibition in the AVCN is delayed by an additional synaptic delay with respect to the excitation. Delayed, frequency-specific inhibition allows the first wavefront to be transmitted to higher auditory centers by bushy and stellate cells, while following inputs encoding signals of similar frequencies are attenuated at least for the duration of an IPSP. These findings are consistent with results from psychoacoustic experiments and suggest that this circuit provides a source of monaural echo suppression.
Identification of serine 473 as a major phosphorylation site in the neurofilament polypeptide NF-L
Authors: Xu ZS , Liu WS , Willard M
Published: March 2018

Neurofilaments are composed of 3 polypeptides designated NF-H, NF-M, and NF-L, all of which are subject to posttranslational phosphorylation. It has been suggested that phosphorylation of the NF-L polypeptide can influence the assembly of NF-L into filaments, but the sites at which NF-L is phosphorylated are unknown. To locate these phosphorylation sites, we have identified phosphopeptides of NF-L by labeling them with 32P both in vitro and in cultured neurons and also by observing their change in chromatographic behavior after they have been treated with phosphatase. We report here that serine 473, in the carboxy-terminal tail domain of NF-L, is a major substrate in vitro for protein kinases endogenous to a crude cytoskeleton-containing fraction. Moreover, serine 473 is a major phosphorylation site in vivo; in neurofilaments isolated from rat spinal cord, approximately 73% of serine 473 was phosphorylated, and accounted for at least one-third of the total phosphate associated with NF-L. The identification of this phosphorylation site in NF-L provides a criterion for identifying the protein kinase that phosphorylates NF-L and raises the question of its function.
Altered slow axonal transport and regeneration in a myelin-deficient mutant mouse: the trembler as an in vivo model for Schwann cell-axon interactions
Authors: de Waegh S , Brady ST
Published: March 2018

The thickness of the myelin sheath in normal myelinated nerve is proportional to the diameter of the axon. In the demyelinating mutant mouse, Trembler, not only is the thickness of the myelin sheath reduced, but the caliber of associated axons is smaller. This correlation suggests that the interaction between axons and Schwann cells may affect the shape and function of axons as well as properties of myelin. Since axonal diameter depends in part on the cytoskeleton and its movement with slow axonal transport, we have compared the properties of slow transport in the sciatic nerve of control and Trembler mice. Studies of the sciatic nerve of normal mice showed that the rates for proteins moving in slow component a (SCa) and slow component b (SCb) are similar to those previously measured in rat. In Trembler mice, tubulin was transported significantly faster than in control mice, with a rate of 1.73 mm/d for Trembler compared to 1.56 mm/d in the control. In contrast, the rate for neurofilament proteins was significantly slower in the Trembler (1.15 mm/d compared to 1.38 mm/d in the control). The majority of proteins in SCb were also transported slower in Trembler than control: actin and calmodulin were transported at 2.29 mm/d as compared to 2.73 mm/d in control, while spectrin and clathrin were transported at 2.01 and 2.43 mm/d, respectively, as compared to 2.54 mm/d in control. The importance of slow axonal transport in regeneration has been suggested by the clear correlation between the rates of regeneration and the rates of SCb. Therefore, we evaluated regeneration of motor axons in Trembler mice to determine whether the regenerative response was affected by deficient Schwann cells. A slower regeneration rate was found in the Trembler (1.7 mm/d) motor axon when compared to the control (2.29 mm/d), but elongation of fibers in regeneration began after a shorter delay in the Trembler (1.6 d) than in control (2.5 d). Thus, deficient Schwann cells and poor myelination appear to affect both quantitative and qualitative properties of slow axonal transport. These changes lead to alterations in the morphological and physiological properties of affected axons.
Postnatal construction of neural circuitry in the mouse olfactory bulb
Authors: Pomeroy SL , LaMantia AS , Purves D
Published: March 2018

We have undertaken a quantitative analysis of the mouse olfactory bulb to address several major questions concerning the development of neural circuitry in the postnatal mammalian brain. These are: (1) To what degree are new elements and circuits added during maturation? (2) How long do such processes go on? and (3) Does postnatal development involve a net addition of circuits and their constituent elements, or is there elimination of some portion of an initial surfeit? Using male mice of known age, weight, and length, we measured the overall size of the bulb, the numbers of processing units (glomeruli) within the bulb, the extent and complexity of postsynaptic dendrites within the glomeruli, and the number of synapses in different regions of the bulb. Between birth and the time mice reach sexual maturity at 6–7 weeks of age, the bulb increases in size by a factor of 8, the number of glomeruli by a factor of 4–5, the length of mitral cell dendritic branches by a factor of 11, and the number of glomerular and extraglomerular synapses by factors of 90 and 170, respectively. Each of these parameters increases steadily from birth, in concert with the enlargement of the olfactory mucosa, the overall growth of the brain, and indeed, of the entire animal. We found no evidence of an initial surfeit of processing units, dendritic branches, or synapses. Further elaboration of neural circuitry by each of these measures is also apparent from the time of sexual maturity until the animals reach their full adult size at about 10–12 weeks of age. The developmental strategy in this part of the mouse brain evidently involves prolonged construction that persists until the growth of the body is complete. This ongoing elaboration of neural circuitry in the postnatal mammalian brain may be relevant to understanding a number of unexplained developmental phenomena, including critical periods, the ability of the juvenile brain to recover from injuries that would cause severe and permanent deficits in older animals, and the special ability of the maturing brain to encode large amounts of new information.
Activation kinetics of retinal cones and rods: response to intense flashes of light
Authors: Hestrin S , Korenbrot JI
Published: March 2018

Cone photoreceptors are less sensitive to light and the duration of their photoresponse is shorter than that of rods. In salamander rods and cones, we identified 3 components in membrane currents activated by bright flashes of light: an early receptor current (ERC) resulting from charge displacement within visual pigments, a saturation photocurrent generated by the closure of the cGMP-sensitive channels, and a putative Na-Ca exchanger current. The time courses of both the ERC and the onset of the saturation photocurrent were similar in rods and cones. The putative Na-Ca exchanger current, on the other hand, is 4- to 8-fold faster in cones. The onset of the saturation photocurrent consisted of a delay followed by a fast relaxation with an exponential time course. In both photoreceptor types the delay and the time course of the fast relaxation are dependent on light intensity and reach a limiting value when about 1% of the photopigment is bleached. The limiting value of the delay, about 8 msec, and of the relaxation time constant, about 2 msec, are nearly identical in rods and cones. The near identity of these parameters implies that at least 2 kinetic steps in the activation response of rods and cones are quantitatively similar. These findings suggest that the functional differences between rods and cones may arise from disparities in the processes that restore the components of the phototransduction cascade to their dark level and not from differences in the activation processes.
The firing of hippocampal place cells in the dark depends on the rat's recent experience
Authors: Quirk GJ , Muller RU , Kubie JL
Published: March 2018

Hippocampal “place cells” fire when a freely moving rat is in a given location. The firing of these cells is controlled by visual and nonvisual environmental cues. The effects of darkness on the firing of place cells was studied using the task of Muller et al. (1987), in which rats were trained to chase randomly scattered food pellets in a cylindrical drum with a white cue-card attached to the wall. The position of the rats was tracked via an infrared LED on the headstage with a video system linked to computer. Two experimental protocols were used: in the first, lights were turned off after the rat had already been placed in the chamber; in the second, the rat was placed in the darkened chamber. The dark segments produced by these 2 methods were identical with respect to light and other cues but differed with respect to the rat's experience. The firing patterns of 24 of 28 cells were unaffected by darkness when it was preceded by a light period. In contrast, the firing patterns of 14 of 22 cells changed dramatically when the rats were put into the darkened chamber. Furthermore, the majority of cells that changed their firing pattern in initial darkness maintained that change when the lights were turned on. These results show that place cells can fire differently in identical cue situations and that the best predictor of firing pattern is a combination of current cues and the rat's recent experience. The results are discussed in terms of mnemonic properties of hippocampal cells and “remapping” of place cell representations.
Tachykinins and calcitonin gene-related peptide enhance release of endogenous glutamate and aspartate from the rat spinal dorsal horn slice
Authors: Kangrga I , Randic M
Published: March 2018

The effects of dorsal root stimulation and of substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP) on the basal release of 9 endogenous amino acids, including glutamate (Glu) and aspartate (Asp), have been investigated using the rat spinal cord slice-dorsal root ganglion preparation and high-performance liquid chromatography with fluorimetric detection. High-intensity repetitive electrical stimulation of a lumbar dorsal root produced a Ca2(+)- dependent increase in the basal release of Asp, Glu, glycine (Gly), serine (Ser), and threonine (Thr). Low concentrations of SP (2 x 10(-7) M) caused a selective increase in the rate of basal release of Glu, whereas higher concentrations (1–5 x 10(-6) M) produced, in addition, an increase in the basal release of Asp. The SP-induced increase of Glu persisted in the absence of external Ca2+, but the effect was blocked by (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP, an SP analog claimed to be an antagonist of the synthetic SP. NKA (5 x 10(-7) - 10(-6) M), a related tachykinin coexpressed with SP in primary sensory neurons, enhanced the basal release of Gly. CGRP (10(-7) M) caused a significant, largely Ca2(+)-independent increase in the basal release of Glu and Asp and a decrease in asparagine. SP and CGRP potentiated the electrically evoked release of Glu and Asp. Neonatal capsaicin treatment did not significantly alter the basal efflux of 9 endogenous amino acids from the spinal slices, but it prevented the dorsal root stimulation-evoked release of Asp, Glu, Gly, and Thr and the SP-induced increase in the basal release of Glu. However, the effect of CGRP was not significantly modified by the capsaicin treatment. These results indicate that tachykinins (SP and NKA) and CGRP are capable of modulating the basal and electrically evoked release of endogenous Glu and Asp, and these actions may provide an important mechanism by which the peptides contribute to the regulation of the primary afferent synaptic transmission. The enhancement of the basal and the dorsal root stimulation-evoked release of Glu and Asp by tachykinins and CGRP may have important physiological implications for strengthening the synaptic connections in the spinal dorsal horn.