bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequence of pedal peptide: a novel neuropeptide from the central nervous system of Aplysia
Authors: Lloyd PE , Connolly CM
Published: March 2018

We report the identification of a novel neuropeptide from Aplysia nervous tissue. The peptide was termed Pedal peptide (Pep) because it was predominantly synthesized in the pedal ganglia. Pep was purified and sequenced from pooled extracts of pedal ganglia. The following sequence was proposed: Pro-Leu-Asp-Ser-Val-Tyr-Gly-Thr-His-Gly-Met-Ser- Gly-Phe-Ala. Enzymatic hydrolysis procedures indicated that Pep had a free carboxyl terminal. A peptide with the proposed sequence was synthesized and compared with the native peptide. Chromatographic properties of the 2 peptides under 3 different conditioned were compared and found to be identical. Electrophysiological responses to the 2 peptides were compared on an identified neuron in the abdominal ganglia and found to be qualitatively and quantitatively very similar. Both peptides produced net inward currents that were associated with a decrease in membrane conductance. The results from these 2 procedures confirmed that the proposed Pep sequence was correct. Quantitative measurements of the incorporation of 35S-methionine into Pep suggest that cell bodies that synthesize Pep were present predominantly in the pedal ganglia but should also be found in other central ganglia as well. Pep-like immunoreactive neurons are found predominantly in the pedal ganglia and less frequently in the other ganglia (Pearson and Lloyd, 1989). Quantitatively, Pep constitutes one of the predominant peptides in the nervous system of Aplysia. Pep does not appear to be a member of any other previously identified invertebrate or vertebrate peptide family.
Inositol 1,4,5-trisphosphate receptor binding: autoradiographic localization in rat brain
Authors: Worley PF , Baraban JM , Snyder SH
Published: March 2018

Inositol 1,4,5-trisphosphate is a second messenger generated by stimulation of the phosphoinositide cycle, thought to release calcium from intracellular stores. We have mapped the distribution of 3H- inositol 1,4,5-trisphosphate receptor binding sites in rat brain by autoradiographic techniques. The cerebellum contains the highest level of inositol 1,4,5-trisphosphate binding sites in brain, which appear to be selectively localized to Purkinje cells. Moderate levels of binding sites are present in the hippocampus, cerebral cortex, caudate, and substantia nigra. Lesion studies indicate that binding in the hippocampus is restricted to intrinsic neuronal elements and in the nigra is found on terminals of the striatonigral projection. Overall, the autoradiographic distribution of inositol 1,4,5-trisphosphate receptors resembles the distribution of phorbol ester binding sites associated with protein kinase C. However, the inositol 1,4,5- trisphosphate receptor has a more restricted distribution since it is not detectable in the spinal cord or olfactory bulb, regions with substantial levels of protein kinase C.
The two major phosphoproteins in growth cones are probably identical to two protein kinase C substrates correlated with persistence of long- term potentiation
Authors: Nelson RB , Linden DJ , Hyman C , Pfenninger KH , Routtenberg A
Published: March 2018

Regulation of neural protein kinase C (PKC) activity appears to directly affect the persistence of long-term potentiation (LTP; Akers and Routtenberg, 1985; Lovinger et al., 1985, 1986, 1987; Routtenberg et al., 1985, 1986; Akers et al., 1986; Linden et al., 1987), a model of neural plasticity (Bliss and Lomo, 1973). In addition, the in vitro phosphorylation of a brain-specific PKC substrate, protein F1 (Mr 47 kDa, pl 4.5), has been directly correlated with persistence of LTP (Lovinger et al., 1986). Because PKC has been implicated in neurite outgrowth and is present at high levels in growth cone-rich areas of fetal brain, we investigated and characterized PKC substrates in a preparation of isolated nerve growth cone fragments from fetal rat brain and compared them with PKC substrates found in adult rat hippocampus. Four major proteins in the growth cone preparation showed endogenous phosphorylation levels at least 10-fold greater than any other phosphoproteins. Three of these 4 phosphoproteins, termed pp40, pp46, and pp80 (Katz et al., 1985), were phosphorylated by exogenous PKC in a dose-dependent manner, indicating that PKC activity might be of particular importance relative to other kinases in growth cone function. The 2 most highly labeled PKC substrates, pp46 and pp80, comigrated on 2-dimensional gels with the adult hippocampal proteins F1 and “80k” (Mr 78–80 kDa, pl 4.0), respectively. In addition, similarities in charge heterogeneity, 2-dimensional phosphopeptide maps, and increased phosphorylation in the presence of exogenous PKC or PKC stimulators suggest that protein F1 and 80k are highly homologous to, if not identical to, pp46 and pp80, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Signaling properties of Ascaris motorneurons: graded active responses, graded synaptic transmission, and tonic transmitter release
Authors: Davis RE , Stretton AO
Published: March 2018

The commissural motorneurons of the nematode Ascaris are capable of transmitting signals passively over long distances with little decrement. This ability is due to the high resistivities of their membranes (Davis and Stretton, 1989). Although these cells rely on their passive properties for long-distance signaling, voltage-sensitive channels are present in commissural membranes. These channels underlie the graded active responses that can be elicited at the offset of abrupt hyperpolarizing and depolarizing intracellular current pulses. The inhibitory motorneurons generate membrane potential oscillations when they are strongly depolarized. All-or-none action potentials have never been observed to occur spontaneously, nor has it been possible to evoke them even when the cells have been strongly hyperpolarized to remove any possible channel inactivation. Our findings indicate that the typical all-or-none action potentials so commonly used in nerve cells throughout the animal kingdom do not occur in these cells. Synaptic transmission is therefore mediated without spikes and is graded. The resting potentials of Ascaris motorneurons lie where the synaptic input-output curves are steepest, above the threshold for release of neurotransmitter. Tonic transmitter release from commissural motorneurons may be the neural mechanism underlying the hydrostatic skeleton of Ascaris.
Postnatal development of glutamatergic, GABAergic, and cholinergic neurotransmitter phenotypes in the visual cortex, lateral geniculate nucleus, pulvinar, and superior colliculus in cats
Authors: Fosse VM , Heggelund P , Fonnum F
Published: March 2018

We have analyzed the postnatal development of glutamatergic/aspartergic, GABAergic, and cholinergic neurotransmitter systems in the visual cortical Areas 17 and 18, lateral geniculate nucleus (LGN), pulvinar, and the visual and non-visual parts of superior colliculus (SC) in kittens. High-affinity uptake of D- aspartate (HA D-Asp), glutamate decarboxylase (GAD), and choline acetyltransferase (ChAT) activities were measured as a means of probing the development of the respective transmitter systems. HA D-Asp exceeded the adult level several-fold in all areas during the postnatal period which corresponded with the period of maximal dendritic/axonal branching patterns and synapse densities in the respective regions. GAD exhibited a gradual increase towards adult levels during the first month. The adult level was reached during postnatal week (PNW) 5–6 in Areas 17 and 18, during PNW3 within LGN, pulvinar, and the visual part of SC. In the nonvisual part of SC, the adult GAD level was reached as early as PNW2. ChAT exhibited biphasic developmental profiles in Areas 17 and 18. An initial peak of near adultlike activity in PNW2 was followed by a decline and subsequently by a slow increase towards adult levels during PNW5–17. ChAT developed very slowly in LGN and pulvinar, and in the latter structure only approximately 70% of the adult activity had been attained by PNW17. In both subdivisions of SC, ChAT had reached adult levels during PNW3–5. Dark-rearing from birth until PNW6 moderately attenuated GAD development in all areas and increased ChAT activity in Areas 17 and 18 but did not affect development of HA D- Asp in any part of the kitten visual system. Our neurochemical findings in the developing cat visual system are consistent with available evidence regarding localization of neurotransmitter systems, as well as postnatal changes in terms of cytoarchitectonics, synaptogenesis, functional development, and susceptibility to neonatal dark-rearing in visual pathways.
Kinesthetic and visual control of a bimanual task: specification of direction and amplitude
Authors: Flanders M , Cordo PJ
Published: March 2018

Kinesthetic information about a perturbation can quickly modify motor activity by producing reflexive compensation. The purpose of the present study was to determine how quickly kinesthetic information about target movement can modify motor activity. Visual information about target movement is known to guide motor activity both quickly and accurately. Therefore, we compared the speed and accuracy of responses to kinesthetically and visually presented targets. Human subjects produced changes in elbow torque as quickly and accurately as possible after the random presentation of 1 of 8 target torques. Information about the direction and amplitude of the target torque was provided either kinesthetically or visually. Responses to kinesthetic targets started at an average latency of 150 msec, and after an additional 159 msec, these responses became accurately graded according to target amplitude. Responses to visual targets started at an average latency of 250 msec, and after an additional 208 msec, these responses became accurately graded according to target amplitude. The accuracy of responses to kinesthetic targets was very similar to the accuracy of responses to visual targets. We conclude that the neural processing of kinesthetic information about target movement is sufficiently fast and accurate to guide typical motor activities.
Interruptions of fictive scratch motor rhythms by activation of cutaneous flexion reflex afferents in the turtle
Authors: Currie SN , Stein PS
Published: March 2018

A low-spinal immobilized turtle displays a fictive scratch reflex in hindlimb muscle nerves in response to mechanical stimulation of specific regions of the shell (Robertson et al., 1985). There are 3 forms of the scratch reflex: the rostral, the pocket, and the caudal; each exhibits rhythmic activation of hindlimb motor neurons. Cutaneous stimulation of the distal hindlimb elicits a fictive flexion reflex that exhibits tonic excitation of hip protractor (flexor) motor neurons and tonic inhibition of knee extensor motor neurons (Stein et al., 1982). In the present study, we describe the motor pattern blends that resulted from transient activation of either the ipsilateral or the contralateral flexion reflex pathway during ongoing scratch motor patterns. Two types of blends were observed: (1) insertions of a flexion reflex synergy into an interrupted scratch cycle and (2) deletions of parts of a scratch cycle. Associated with each type of motor pattern blend was a permanent reset of the ongoing scratch rhythm. The sign of the reset (phase-advance or phase-delay) could be predicted for all forms of the scratch based on the location of the foot stimulus (ipsi- or contralateral) and its timing relative to the hip protractor/retractor cycle. The timing of knee extensor activity within the hip cycle is different for each form of the scratch (Robertson et al., 1985); thus, the sign of the reset cannot be predicted from the timing of the stimulus relative to the knee extensor cycle. These results indicate the importance of the hip rhythm in determining the overall timing of the scratch reflex.(ABSTRACT TRUNCATED AT 250 WORDS)
Peripheral target choice by homologous neurons during embryogenesis of the medicinal leech. I. Segment-specific preferences of Retzius cells
Authors: Loer CM , Kristan WB
Published: March 2018

A pair of large serotonergic neurons, the Retzius (Rz) cells, is found in each segment of the leech nervous system. Most Rz cells innervate the body wall of their own segment as well as adjacent anterior and posterior segments. Rz cells in segments 5 and 6 [Rz (5,6)] instead innervate the reproductive tissue found only in those segments. Rz cells from adjacent segments [Rz (4,7)] provide the serotonergic innervation of the body wall of segments 5 and 6. During embryogenesis, the body wall and the reproductive tissue are apparently available to both Rz (5,6) and Rz (4,7), yet these neurons choose different targets. We asked how Rz (5,6) and Rz (4,7) choose their respective peripheral targets in the reproductive segments by ablating either the reproductive tissue or specific Rz cells. Ablation of the reproductive tissue caused Rz (5,6) to innervate body wall, although not as proficiently as did standard Rz cells, suggesting a preference of Rz (5,6) for reproductive tissue. Ablation of those Rz cells that would normally innervate the body wall of segments 5 and 6 did not cause Rz (5,6) to innervate body wall, ruling out competition for this target. When Rz (5,6) were ablated, Rz (4,7) innervated the body wall of segments 5 and 6 normally and did not innervate reproductive tissue. Thus, competition did not act in the choice of target by Rz (4,7) either. These results suggest that during normal development, Rz (5,6) and Rz (4,7) choose their targets independently of one another rather than competing for the available targets and that these cells have segment-specific target preferences.
Relationship between phosphorylation and synthesis of goldfish optic nerve proteins during regeneration
Authors: Larrivee DC , Grafstein B
Published: March 2018

After intraocular injection of radiolabeled phosphate and 3H-proline, the labeling of goldfish optic nerve proteins was monitored over a 7 week period of regeneration following a lesion to the optic tract. Labeled phosphate incorporation into total nerve protein increased to a peak value about twice that in normal nerve at 3 weeks after injury, then declined to slightly above normal by 7 weeks. Incorporation of 3H- proline showed a higher rise and a steeper decline, with values still significantly above normal at 7 weeks. Two-dimensional gel electrophoresis revealed that almost all the individual proteins examined underwent an increase in 3H-proline incorporation with a peak at about 3 weeks. However, only 4 proteins showed an increase in incorporation of 32P correlated with the increase in 3H-proline. The closest correlation was seen for protein 4, the equivalent of the growth-associated protein GAP-43; for the other 3 proteins (15, 31, and 38) 32P incorporation remained elevated even when 3H-proline incorporation had declined. Two other proteins (24e and 48) showed increased 32P incorporation not correlated with 3H-proline changes. Several proteins showed a decrease in 32P incorporation, even though 3H- proline incorporation was increased. For example, the phosphorylation of ON2, a neuronal intermediate filament protein, showed a long-lasting decline, which was already evident at 1 week and had not yet returned to normal by 7 weeks. Other proteins in this group (33, 37, and 46) showed a faster recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
Differentiation of axon-related Schwann cells in vitro: II. Control of myelin formation by basal lamina
Authors: Eldridge CF , Bunge MB , Bunge RP
Published: March 2018

Several recent observations suggest that Schwann cell (SC) differentiation, including myelin formation, is dependent upon the development of basal lamina which characteristically surrounds each axon-SC unit in peripheral nerve. This dependence can be tested in a neuron-SC culture system developed in our laboratory in which SC differentiation, including basal lamina formation and myelination, is faithfully reproduced. The use of serum-free, defined medium (DM) with this culture system allows axon-driven SC proliferation but not basal lamina formation or myelination. We previously demonstrated that ascorbic acid, in the presence of a nondialyzable serum factor(s), stimulates basal lamina assembly and myelin formation with similar dose- response relationships (Eldridge et al., 1987). We hypothesized that ascorbic acid acts to promote SC myelination indirectly, by enabling the assembly of basal lamina. We now provide support for this hypothesis by demonstrating the following. (1) Pepsin-resistant triple- helical collagen molecules were produced only by SCs grown in the presence of ascorbic acid, suggesting that triple-helical type IV collagen may mediate the effect of ascorbic acid on basal lamina formation. (2) The formation of myelin by oligodendrocytes, which myelinate axons in the CNS without the concomitant deposition of basal lamina, was little affected by ascorbic acid, suggesting that the biosynthesis and assembly of myelin per se does not require ascorbic acid. (3) The provision of exogenous basal lamina matrix to SCs grown with neurons in DM without ascorbic acid promoted control levels of myelination (and basal lamina formation); the provision of exogenous fibrillar collagen matrix did not. (4) Purified laminin promoted control levels of myelination in the absence of ascorbic acid, but purified type IV collagen and heparan sulfate proteoglycan (HSPG) did not. Laminin caused SCs to assemble basal lamina-like structures that contained not only laminin but also HSPG and non-triple-helical type IV collagen. Thus, several types of experiments demonstrate that SC myelin formation can be controlled by regulating the ability of the SC to assemble basal lamina, illustrating that acquisition of basal lamina is a crucial prefatory step for further SC differentiation.
G proteins couple alpha-adrenergic and GABAb receptors to inhibition of peptide secretion from peripheral sensory neurons
Authors: Holz GG , Kream RM , Spiegel A , Dunlap K
Published: March 2018

Regulation of neuronal calcium channels by GTP-binding proteins (G proteins) is likely to be an important mechanism by which inhibitory transmitters influence excitation-secretion coupling in presynaptic nerve endings. Here, we report that in peripheral sensory neurons from embryonic chick dorsal root ganglia (DRG), the G protein-mediated inhibition of voltage-dependent calcium channels may best explain how norepinephrine (NE) and GABA inhibit the electrically evoked, calcium- dependent release of substance P (SP). As is the case for the previously reported inhibitory actions of these transmitters on DRG cell calcium channels, we demonstrate that NE and GABA inhibit peptide secretion through activation of alpha-adrenergic and GABAb receptors that are functionally coupled to pertussis toxin (PTX)-sensitive G proteins. Pretreatment of DRG cell cultures with PTX blocked the ability of NE and GABA to inhibit the release of SP, an action correlated with PTX-catalyzed ADP-ribosylation of membrane proteins with apparent molecular weight (Mr) of 40–41 kDa. Western immunoblot analysis of chick DRG cell membrane proteins using antisera directed against synthetic peptides corresponding to amino acid sequences predicted from cDNAs for PTX-sensitive G protein alpha subunits revealed a minimum of 2 Gi-like proteins (Mr 40 and 41 kDa) and a third Go-like protein (Mr 40 kD). Significantly, these findings implicate Gi- and/or Go-like GTP-binding proteins as mediators of presynaptic inhibition in peripheral sensory neurons.
Chromatic and achromatic vision of macaques: role of the P pathway
Authors: Merigan WH
Published: March 2018

Chromatic and achromatic contrast sensitivity were measured in a human observer, 2 normal macaque monkeys, and 3 monkeys with severe toxicant- induced damage to the parvocellular projecting retinogeniculate pathway (P cell-deficient monkeys). Damage to the P pathway was produced by the oral administration of acrylamide monomer (Eskin and Merigan, 1986). Contrast sensitivity was measured in all subjects with isochromatic luminance gratings, as well as isoluminant chromatic gratings, modulated along several directions of a color space that represents color-opponent and luminance contrast (Krauskopf et al., 1986). The chromatic and achromatic sensitivity of the control monkeys was virtually identical to that of the human observer. Chromatic sensitivity of the P cell-deficient monkeys, measured at a low spatial frequency (0.3 c/deg), along a constant-blue color axis, was 0.9–1.5 log units lower than that of controls. Similar losses were seen along a tritanopic confusion axis and along 2 intermediate axes of color direction. Chromatic thresholds measured at higher spatial frequency (2.0 c/deg) were similarly reduced. Counterphase-modulated chromatic gratings were used to test color sensitivity over a range of temporal frequencies up to 15 Hz, and the loss of color vision was substantial over the entire range of frequencies. The luminance contrast sensitivity of the P cell-deficient monkeys for stationary gratings decreased after exposure by 0.5–0.8 log units. These results indicate that the chromatic and achromatic spatial vision of macaques is very similar to that of humans. They also suggest that the P pathway plays an important role in macaque chromatic sensitivity at all spatial frequencies, as well as achromatic sensitivity at high spatial and lower temporal frequencies.
Open channel structure and ion binding sites of the nicotinic acetylcholine receptor channel
Authors: Dani JA
Published: March 2018

Clonal BC3H-1 muscle cells were studied using patch-clamp techniques. The structure and ion binding sites of the nicotinic ACh receptor channel were examined by measuring permeability ratios and streaming potentials. The permeability ratio of lithium to ammonium remained constant from 10 to 150 mM. That result indicates there is one primary binding site in the narrowest region of the channel over the concentration range tested. There are, however, other binding sites and many ions in the large entrance vestibules. The sites in the wider regions of the channel influence ionic permeation, but the main determinant of transport is the site directly in the permeation pathway. An estimate of the length of the narrow region was obtained from streaming potential measurements. The streaming potential is directly related to the number of water molecules coupled to the transport of a permeant ion through the pore. Under proper experimental conditions, streaming potential measurements indicated that the narrowest cross section of the pore holds only about 6 water molecules. Therefore, the narrowest cross section is very short, and it contains one main binding site. The overall results are consistent with the pore being lined by transmembrane helices with a low charge density. Since the open pore has a short narrow region, the helices that rim the pore may spread out from the narrowest cross section. The widening of the pore would expose a second set of transmembrane helices at the interstices between the first set of helices.
Deficits in response space following unilateral striatal dopamine depletion in the rat
Authors: Brown VJ , Robbins TW
Published: March 2018

Hungry rats were trained to report the occurrence and location of brief, unpredictable visual stimuli presented to the left of their heads in 1 of 2 response locations. After training, they received unilateral infusions of 6-hydroxydopamine, depleting dopamine throughout the head of the caudate putamen, either on the left or the right side, that is, either ipsilateral or contralateral to the side on which they were required to respond. Following an ipsilateral lesion there were no impairments in localization of the visual discriminanda and there was no lengthening of reaction time. The contralaterally lesioned rats, however, showed considerably lengthened reaction times to both stimuli and a profound bias to the nearer of the 2 response locations. Evidence from probe trials in which the visual stimuli were presented separately or simultaneously showed that the impairment was not due to a failure to localize the stimuli in contralateral space but, rather, resulted from a deficit in directing responses in contralateral space. It is suggested that this may be due to a distortion in the representation of response space.
Biosynthesis of adipokinetic hormones (AKHs): further characterization of precursors and identification of novel products of processing
Authors: Hekimi S , O'Shea M
Published: March 2018

Two adipokinetic hormones (AKH I: pGlu-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly- Thr-NH2, and AKH II: pGlu-Leu-Asn-Phe-Ser-Thr-Gly-Trp-NH2) are synthesized by the neurosecretory cells of the corpora cardiaca (CC) of the locust Schistocerca gregaria. Both AKHs are released into the blood during flight and serve to regulate lipid metabolism and other physiological processes involved in flight. By in vitro “pulse-chase” experiments we show that 2 precursors (P1 and P2) are involved in AKH biosynthesis. These are about 8.4 kDa polypeptides which are AKH immunoreactive but also contain an amino acid (tyrosine) not present in the AKH peptides. By following the fate of 14C-tyrosine incorporated into P1 and P2, we have identified 2 novel products of precursor processing. These are called AKH-Precursor Related Peptides or APRP 1 and APRP 2. Size exclusion chromatography shows that the APRPs are about 6.5 kDa large and therefore represent major fragments of the precursors. The optical density peaks corresponding to P1, P2, APRP 1, and APRP 2 on a reverse-phase chromatogram are identified. The precursors being metabolic intermediates are represented by minor optical density peaks that disappear when de novo protein synthesis is blocked by cycloheximide. In contrast, the APRPs are represented by major optical density peaks consistent with their being accumulating end products of AKH precursor processing. The function of the APRPs is as yet unknown. They are, however, co-synthesized and also co-released with the AKHs, and may therefore also have hormonal functions related to flight.
Development of saxitoxin-sensitive and insensitive sodium channels in cultured neonatal rat astrocytes
Authors: Yarowsky PJ , Krueger BK
Published: March 2018

Voltage-sensitive Na channels were studied in cultures of neonatal rat cortical astrocytes. These channels were present at all times in culture as determined by tracer 22Na+ influx in the presence of batrachotoxin (BTX) and sea anemone polypeptide toxin (AxTx). The affinity of saxitoxin (STX) binding and sensitivity to STX inhibition of sodium influx were utilized to characterize these channels. Up to 7 d in culture, high-affinity 3H-STX binding (Kd of 0.2 nM at 4 degrees C) was very low, and 22Na+ influx was inhibited only by high concentrations (Ki = 170 nM) of STX. From 7 to 14 d, total specific binding of STX increased to a maximum of over 2 pmol/mg protein and remained constant for 28 d. By 14 d, inhibition of 22Na+ influx by STX was clearly biphasic, indicating the presence of 2 populations of channels with Ki's of 0.2 nM and 150 nM. At 14 d in culture, binding of 3H-STX to astrocyte membranes revealed the presence of 2 specific sites. During this second week, increasing numbers of high-affinity STX binding sites and increasing sensitivity to the inhibition of BTX + AxTx-stimulated 22Na+ influx by STX coincided with the change in morphology of primitive flat polygonal cells to highly branched stellate forms characteristic of mature astrocytes in vivo. Changes in culture conditions modified the time course of the onset of high STX affinity binding. Twenty-four hours after changing to serum-free G5 medium, there was both an 8-fold increase in STX binding sites and a change to a stellate shape in all cells. The results suggest that although low-affinity STX Na channels are always present in astrocytes, after 7 d in culture a different population of channels appears with the high affinity for STX characteristic of adult neuronal sodium channels. This spontaneous process is greatly accelerated by changing to a chemically defined medium.
Long-term expansion and sensitization of mechanosensory receptive fields in Aplysia support an activity-dependent model of whole-cell sensory plasticity
Authors: Billy AJ , Walters ET
Published: March 2018

Long-term changes in peripheral receptive field properties of mechanosensory/nociceptive neurons were investigated 1–3 weeks after noxious stimulation. Noxious stimuli consisted of a deep penetrating cut through the middle of the tail, strong electric shock applied to the tail surface, or a combination of deep and superficial tail stimulation. Action potentials evoked in the tail were monitored with intracellular electrodes in central somata of tail sensory neurons. Three long-term changes in receptive field properties were produced in the region of noxious stimulation: (1) mechanosensory thresholds decreased, (2) receptive field areas increased, and (3) the percentage of cells showing receptive field extension across the tail midline increased. Sizes and shapes of individual receptive fields did not vary during extensive testing of tails perfused with artificial seawater or during testing in cobalt solutions that block synaptic transmission. This stability of receptive field geometry, coupled with the observation that increased peripheral excitability in these cells does not increase receptive field size, suggests that long-term receptive field alterations involve growth of peripheral sensory processes. A model is proposed in which the signaling strength of the entire sensory cell increases in response to trauma of its receptive field. In this model long-term enhancement of central and peripheral sensory responsiveness is selectively triggered by activity dependent extrinsic modulation of the centrally located soma, which accelerates synthesis of growth-associated proteins used in collateral and regenerative sprouting of traumatized peripheral processes.
Postnatal development of the spatial contrast sensitivity of X- and Y- cells in the kitten retinogeniculate pathway
Authors: Tootle JS , Friedlander MJ
Published: March 2018

The sensitivity to spatial contrast patterns of single retinal ganglion cell axons and neurons in the A-layers of the dorsal lateral geniculate nucleus (LGNd) was measured in 4 1/2- and 6 1/2-week-old kittens and adult cats. Drifting sinusoidal grating stimuli were presented at 6–12 spatial frequencies to obtain spatial contrast sensitivity functions (SCSFs). The SCSFs were normalized for the postnatal growth of the kitten eye and were interpreted using a difference of Gaussians model of the receptive field (RF). The average optimal spatial frequency, spatial frequency bandwidth, and the proportion of cells that were selective for spatial frequency did not differ significantly between the kittens and adults for ganglion cells belonging to the cluster 1 (X- ) or cluster 2 (Y-) functional types. The spatial resolution of kitten ganglion cells was also adultlike, except for that of Y-ganglion cells with peripheral RFs, which was significantly higher than in the adult. The spatial resolution of X-LGNd neurons with peripheral RFs was significantly poorer at 4 1/2 weeks than in the older animals. The proportion of X-LGNd neurons that were selective for spatial frequency increased between 4 1/2 and 6 1/2 weeks postnatally, but the spatial frequency bandwidth of selective cells did not change. The increased proportion of spatially selective LGNd neurons is probably due to the maturation of intrageniculate inhibitory circuits. Developmental changes in spatial resolution were interpreted as resulting from an increase (Y-retinal ganglion cells) or decrease (X-LGNd neurons) in RF center size. A model of retinogeniculate development is presented that attributes postnatal expansion of Y-retinal ganglion cell RF centers to increased functional convergence from more distal retinal neurons and reduction in LGNdX-cell RF center size to decreased convergence from X- retinal ganglion cells.
The medullary pacemaker nucleus is unnecessary for electroreceptor tuning plasticity in Sternopygus
Authors: Ferrari MB , Zakon HH
Published: March 2018

Tuberous electroreceptors of the weakly electric fish Sternopygus macrurus are closely tuned to the frequency of electric organ discharge (EOD), which is determined by a medullary pacemaker nucleus (PMN). Previous studies have demonstrated that androgens lower the frequency of PMN discharge and concomitantly lower the best frequencies (BFs) of electroreceptors. In order to determine if the PMN serves as an internal reference for the hormone-mediated returning of electroreceptors, the PMN was lesioned and the change in mean BF was measured for dihydrotestosterone (DHT)-implanted or control animals. DHT-implanted fish showed the characteristic lowering of mean electroreceptor BF by approximately 25%, a significant change compared with controls (p less than 0.01, Mann-Whitney). This result indicates that the PMN is not necessary for the hormone-mediated shift of electroreceptor tuning. In a related study, the contribution of the PMN to the genesis of tuning in regenerating electroreceptors was examined by removing a patch of cheek skin from PMN-lesioned fish. Regenerating electroreceptors became sharply tuned to the previous EOD frequency by 6 weeks in the same fashion as regenerating receptors in intact fish. In addition, intact receptors from PMN-lesioned fish remained tuned for up to 160 d. Together, these results demonstrate that the pacemaker nucleus is unnecessary for the maintenance, development, or hormone- mediated shift of receptor tuning.
Properties of appropriately and inappropriately expressed sodium channels in squid giant axon and its somata
Authors: Gilly WF , Brismar T
Published: March 2018

Neurons that form the giant axons in squid by axonal fusion in the stellate ganglion are inexcitable and do not express functional voltage- controlled sodium (Na) channels in their somata in vivo. These cells do express Na channels in the soma membrane in vitro, however, provided they have been axotomized. We describe here voltage-clamp experiments on the isolated cell bodies maintained in primary culture and on acutely isolated giant axons designed to compare the functional properties of the Na channels expressed inappropriately in the soma with those of channels expressed normally in the axon. Approximately 85% of Na channels in the soma are essentially indistinguishable from those in the giant axon with regard to gating properties and sensitivity to tetrodotoxin or saxitoxin. Thus, the isolated soma is capable of processing Na channels to a state of apparent functional perfection. In addition to these normal Na channels, another type is regularly expressed in the cultured somata. This second type lacks inactivation and is preferentially sensitive to block by cadmium ions, but is otherwise indistinguishable from the more prevalent normal type of channels.
Local circuits and ocular dominance columns in monkey striate cortex
Authors: Katz LC , Gilbert CD , Wiesel TN
Published: March 2018

The relationships between ocular dominance columns and intrinsic cortical circuitry were examined in brain slices prepared from the striate cortex of macaques. Ocular dominance columns in layer 4C beta were visualized in vitro following anterograde transport of rhodamine injected into the lateral geniculate nucleus in vivo. The axonal and dendritic arborizations of individual layer 4C beta cells were revealed by intracellular fluorescent dye injections. Both qualitative observations and quantitative analysis showed that the dendrites of cells close to borders remained preferentially, although not absolutely, in the “home” column (the column containing the cell body). Thus, the segregated pattern of afferent input appears to have considerable influence on the pattern of dendritic arbors. Similarly, while axon collaterals within layer 4C beta could cross into the adjacent column, their limited lateral spread produced arbors that remained primarily within the home column. The terminal arbors of collaterals that travelled from layer 4C beta to layer 3 had a larger lateral spread, and the termination pattern appeared to be independent of column borders. Thus, our observations indicate that, while the course of many layer 4C beta dendrites appears to be guided by columnar boundaries as defined by geniculate afferents, there exist morphological substrates for intercolumnar interactions even between 4C beta cells. Intercolumnar interactions are seen more commonly in layer 3, however, where larger, denser axon arbors originating from 4C beta cells can freely cross ocular dominance column boundaries.
Normal numbers of retinotectal synapses during the activity-sensitive period of optic regeneration in goldfish: HRP-EM evidence implicating synapse rearrangement and collateral elimination during map refinement
Authors: Hayes WP , Meyer RL
Published: March 2018

Optic and nonoptic fibers and synapses were counted in the primary optic innervation layer (S-SO-SFGS) in anteromedial tectum in normal goldfish and in fish 30, 60, and 240 d after the optic nerve was crushed. A newly developed “cold-fill” HRP-labeling protocol was used to label optic afferents for electron microscopy, and counts were then made on EM photomontages of columns through the HRP-labeled S-SO-SFGS. Normal numbers of retinotectal synapses were present at 30 d regeneration, at a time when activity-dependent refinement of the optic projection is incomplete. Normal numbers were also found at 60 and 240 d, when refinement is largely completed. In contrast to this constancy in optic synapse numbers, there was nearly 10 times the normal number of optic fibers in the SFGS at 30 d, and these were reduced by 50% at 60 d, remaining over 4 times normal at 240 d. These findings imply extensive rearrangement of optic synapses during map refinement. They also indicate that synapse rearrangement is associated with the elimination of optic collaterals.
Differential effects of fornix and caudate nucleus lesions on two radial maze tasks: evidence for multiple memory systems
Authors: Packard MG , Hirsh R , White NM
Published: March 2018

The present experiments were designed to examine the hypothesis that the mammalian brain contains anatomically distinct memory systems. Rats with bilateral lesions of caudate nucleus or fimbria-fornix and a control group were tested postoperatively on 1 of 2 versions of the radial maze task. In a standard win-shift version, each of the 8 arms of the maze was baited once, and the number of errors (revisits) in the first 8 choices of each trial was recorded. Fimbria-fornix rats were impaired in choice accuracy, while caudate animals were unimpaired relative to controls. Different groups of rats with similar lesions were tested on a newly developed win-stay version of the radial maze, in which the location of 4 randomly selected baited arms was signaled by a light at the entrance to each arm, and which required rats to revisit arms in which reinforcement had been previously acquired within a trial. Rats with fimbria-fornix lesions were superior to controls in choice accuracy on the win-stay radial maze task, while caudate animals were impaired relative to controls. The results demonstrate a double dissociation of the mnemonic functions of the hippocampus and caudate nucleus. Some implications of the presence of 2 memory systems in the mammalian brain are discussed.
The noradrenergic neurotoxin DSP-4 eliminates the coeruleospinal projection but spares projections of the A5 and A7 groups to the ventral horn of the rat spinal cord
Authors: Lyons WE , Fritschy JM , Grzanna R
Published: March 2018

Systemic administration of the noradrenergic neurotoxin DSP-4 results in a complete loss of staining of noradrenergic (NA) axons in the dorsal horn and intermediate zone of the rat spinal cord. NA axon staining in the ventral horn and in the intermediolateral cell column is only slightly decreased by the drug treatment. We have taken advantage of this differential effect of DSP-4 on NA axons to determine the location and number of cells that give rise to NA axons in the ventral horn and the intermediolateral cell column. Retrograde transport of the fluorescent tracer True blue was combined with dopamine-beta-hydroxylase immunohistochemistry 2 weeks after treatment of rats with 50 mg/kg of DSP-4. Compared with controls, the drug treatment resulted in a more than 90% decrease in the number of retrogradely labeled NA neurons in the locus coeruleus and an only 30– 50% reduction in the number of retrogradely labeled NA cells in the A5 and A7 groups. The results reveal different sites of termination in the spinal cord of NA axons originating in the LC and in NA cells of the A5 and A7 groups: the LC distributes fibers mainly to the dorsal horn and the intermediate zone, while NA cells of the A5 and A7 groups project to motoneurons of the ventral horn and the intermediolateral cell column.
Studies of nerve-muscle interactions in Xenopus cell culture: fine structure of early functional contacts
Authors: Buchanan J , Sun YA , Poo MM
Published: March 2018

We have studied the fine structure of nerve-muscle contacts during the first few hours of synaptogenesis in embryonic Xenopus cell cultures. The precise timing of contact was achieved by manipulating isolated spherical myocytes (myoballs) into contact with growth cones or neurites of co-cultured spinal neurons. The contacts were shown to be functional by whole-cell voltage-clamp recording of nerve-evoked synaptic currents in the muscle cell. The ultrastructure of these functional contacts was examined by thin-section electron microscopy. In total, 20 nerve-muscle pairs were studied with contact periods ranging from 20 min to 12 hr, during which time a substantial increase in the amplitude of synaptic currents occurred. The structure of noncontacting cells and of nerve-muscle contacts formed between the cells by natural encounters in 1-d-old cultures were also examined in order to identify the features and the time course of morphological differentiation of early functional contacts. Prominent features of the contact area during the first few hours included: close apposition of the nerve and muscle membranes, greater frequency of coated pits and vesicles, and thickening of postsynaptic muscle membrane. Occasionally, clusters of clear vesicles occurred near presynaptic membrane, but no further sign of active zone differentiation was observed. In comparison, definitive active zone structure, well-formed extracellular basal lamina, and widened cleft were seen in natural contacts less than 24 hr old. This study of the identified functional contacts may help us to understand the structural basis for early nerve-muscle interaction and the functional significance of various synaptic specializations.
A modulatory proctolin-containing neuron (MPN). I. Identification and characterization
Authors: Nusbaum MP , Marder E
Published: March 2018

The pentapeptide proctolin has been localized previously to the crustacean stomatogastric nervous system and shown to modulate the rhythmic activity of the pyloric network in the stomatogastric ganglion (STG) (Marder et al., 1986; Hooper and Marder, 1987). We have now identified a pair of modulatory proctolin-containing neurons (MPNs) that cause proctolin-like modulation of the pyloric rhythm. Individual MPNs were identified by combining intracellular Lucifer yellow dye injection with rhodamine-visualized proctolin immunolabeling. Both MPNs are located in the esophageal nerve and send processes to the STG. Current injection into one MPN influences the second MPN, suggesting that they are electrically coupled. The 2 MPNs have similar effects on the pyloric rhythm of the STG. Intracellular stimulation of a single MPN was sufficient to enhance already active pyloric rhythms and initiated the pyloric rhythm in quiescent preparations.
A modulatory proctolin-containing neuron (MPN). II. State-dependent modulation of rhythmic motor activity
Authors: Nusbaum MP , Marder E
Published: March 2018

The effects of stimulating the modulatory proctolin-containing neurons (MPNs) on the pyloric rhythm of the stomatogastric ganglion of the crab, Cancer borealis, were compared with those produced by exogenously applied proctolin. The effects of both MPN stimulation and proctolin applications depend on the preceding physiological state of the preparation. Both treatments increase the pyloric cycle frequency dramatically in preparations that are slowly cycling, but they have little or no effect on pyloric cycle frequency in preparations that are already rapidly cycling. MPN and proctolin produce maximal pyloric cycle frequencies of about 1.2 Hz, although much faster pyloric frequencies are possible. MPN stimulation and proctolin applications affect the number of impulses fired in each burst by pyloric network neurons. MPN's excitatory actions are longer lasting when a preparation is active than when it is quiescent before stimulation. These data suggest that many of MPN's physiological actions result from its release of proctolin. Small unitary postsynaptic potentials evoked by MPN stimulation in the lateral pyloric neuron may indicate the presence of a second neurotransmitter in MPN.
Selective elimination of cross-compartmental innervation in rat lateral gastrocnemius muscle
Authors: Donahue SP , English AW
Published: March 2018

The calf muscles of the rat hindlimb are composed of smaller entities, called neuromuscular compartments, which are the territories of muscle innervated by a single, naturally occurring primary (first-order) muscle nerve branch. While it is quite clear that a precise connectivity exists very early in development between motoneuron pools and individual muscles, the mechanisms responsible for producing the adult pattern of compartmental innervation are unknown. This study uses intracellular recording techniques to demonstrate that neuromuscular compartments are essentially established at birth and that postnatal synapse elimination has little role in establishing neuromuscular compartments. Our results demonstrate the existence of a small number of cross-compartmental connections in neonates which are not present in adults. Examining the removal of these cross-compartmental connections in both normal muscles and in muscles that have had synapse elimination delayed by tenotomy reveals that the synapses responsible for this innervation are eliminated in a selective manner.