bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting and activity-related dendritic modification in mammalian retinal ganglion cells
Authors: Wingate RJ , Thompson ID
Published: April 2018

We have studied factors that influence the development of dendritic morphology in hamster retinal ganglion cells. By combining fluorescent retrograde tracing with in vitro Lucifer yellow injection into fixed retina, cells with appropriate and inappropriate visuotopic projections have been compared. In adult hamsters, cells with an aberrant ipsilateral projection from the nasal retina display a uniformly sparse dendritic morphology. However, following monocular enucleation at postnatal day 0 (P0), this population displays a significantly enhanced dendritic complexity in the adult. By contrast, removal of one eye at P6 or at P12 produces progressively less effect. These results suggest that dendritic complement of the adult aberrant projection can be regulated by altering the early postnatal axonal environment. The development of aberrant ganglion cells was investigated to determine the relative influences of cell death and dendritic remodeling in shaping the composition of the adult aberrant population. Aberrant cells were found to be indistinguishable from other cells in nasal retina throughout early development. After ganglion cell death (P1-P12) is over, aberrant cells still display a full range of cell types. However, at eye opening (P16) they undergo a rapid loss of dendritic complexity by remodeling. By P22, aberrant cells display a uniformly sparse dendritic morphology. When hamsters were raised in the dark between P12 (the end of ganglion cell death) and P22, this severe remodeling was blocked. This block was maintained when hamsters were dark reared to P42. Hence, both dark rearing and monocular enucleation at P0 produce similar effects on the development of visuotopically inappropriate hamster retinal ganglion cells. We speculate that the patterns of dendritic sculpting that we have observed reflect activity- mediated modulation of dendritic form via retrograde signals from the terminal arbors. This has implications for retinal ganglion cell morphological classification and, more generally, for mechanisms that influence the dendritic development of other neurons in the CNS.
N-type Ca2+ channels are located on somata, dendrites, and a subpopulation of dendritic spines on live hippocampal pyramidal neurons
Authors: Mills LR , Niesen CE , So AP , Carlen PL , Spigelman I , Jones OT
Published: April 2018

In the nervous system the influx of Ca2+ orchestrates multiple biochemical and electrical events essential for development and function. A major route for Ca2+ entry is through voltage-dependent calcium channels (VDCCs). It is becoming increasingly clear that the precise contribution VDCCs make to neuronal function depends not only upon their specific electrophysiological properties but also on their distribution over the nerve cell surface. One location where the presence of VDCCs may be critical is the dendritic spine, a structure known to be the major site of excitatory synaptic input. On spines, VDCCs are hypothesized to play an essential role in signal processing, learning, and memory. However, direct evidence for the presence of VDCCs on spines is lacking. Attempts to examine the distribution of VDCCs, or indeed any other components, on spines have been hampered since the size of many spines is close to the limits of resolution of conventional light microscopy. Using a new, biologically active, fluorescein conjugate of omega-conotoxin (Fl-omega-CgTx), a selective blocker of N-type VDCCs, and confocal microscopy, we have mapped the distributions of N-type VDCCs on live CA1 neurons in rat hippocampal slices. VDCCs were found on somata, throughout the dendritic arbor, and on dendritic spines in all hippocampal subfields. A comparison of three- dimensional reconstructions of structures labeled by Fl-omega-CgTx with those outlined by 1,1-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine (Dil) or Lucifer yellow confirmed the presence of N-type VDCCs on dendritic spines. However, spine frequency on dendrites labeled with Fl- omega-CgTx was much lower than the spine frequency on dendrites labeled with Lucifer yellow or Dil, suggesting that some spines lack N-type VDCCs. These results offer the first direct evidence for the localization of any voltage-dependent channel on dendritic spines. The presence of N-type VDCCs on dendrites and their spines argues that these channels may participate in the generation of active Ca2+ conductances in distal dendrites, and is consistent with a role for spines as specialized compartments for concentrating Ca2+.
Innervation and vasculature of human sweat glands: an immunohistochemistry-laser scanning confocal fluorescence microscopy study
Authors: Kennedy WR , Wendelschafer-Crabb G , Brelje TC
Published: April 2018

Secreting tubules, nerves fibers, and blood vessels in human sweat glands (SGs) were fluorescently stained by immunohistochemical and lectin methods for examination with a laser scanning confocal microscope (LSCM). Using these techniques, the three-dimensional distribution of up to three substances within a single specimen was investigated by collecting a series of optical sections for each of three fluorophores. Each SG received several nerve fibers. These branched into delicate bands of one or more axons that ran longitudinal to the sweat tubule then encircled the tubule. A heavy complement of capillaries was interwoven among the sweat tubules. Sweat ducts were accompanied from the SG toward the skin surface by one or two longitudinally oriented nerve fibers and capillaries. Immunoreactive staining of nerves was heaviest with protein gene product 9.5 antibody, but triple labeling showed that immunoreactivity to calcitonin gene- related peptide, vasoactive intestinal polypeptide, and synaptophysin was also present in the same axons. Substance P-immunoreactive axons were sparse in SGs but were present in other areas of the skin. The techniques used have considerable potential in examination of human skin biopsies for diagnosis of disorders affecting the somatic and autonomic nervous systems.
Amyloid precursor protein in cortical neurons: coexistence of two pools differentially distributed in axons and dendrites and association with cytoskeleton
Authors: Allinquant B , Moya KL , Bouillot C , Prochiantz A
Published: April 2018

Embryonic cortical neurons in culture contain transmembrane amyloid precursor protein (APP) capable of associating with the detergent- insoluble cytoskeleton through interactions requiring the presence of its C-terminal. These transmembrane APPs are not detectable at the surface of living cells. When neurons are fixed with paraformaldehyde alone, APP is mainly visualized close to the membrane of the axon and cell body of 40% of neurons, with virtually no dendritic staining. Membrane permeabilization with detergent or methanol extends APP immunostaining to 100% of the cells and to all compartments, including the dendrites. Taken together, these results suggest that APP in embryonic neurons is present in two compartments, one more readily detectable in some axons and cell bodies and the other distributed throughout all neurons. The axonal and somatic pool of APP detectable after paraformaldehyde fixation alone is highly and rapidly augmented after exposure to calcium ionophores. We propose that calcium entry increases the amount of axonal APP close to the cell surface, but that the stabilization of the protein at the cell surface and its subsequent secretion require further physiological stimuli.
Interocular suppression in the visual cortex of strabismic cats
Authors: Sengpiel F , Blakemore C , Kind PC , Harrad R
Published: April 2018

Strabismic humans usually experience powerful suppression of vision in the nonfixating eye. In an attempt to demonstrate physiological correlates of such suppression, we recorded from the primary visual cortex of cats with surgically induced squint and studied the responses of neurons to drifting gratings of different orientation, spatial frequency, and contrast in the two eyes. Only 1 of 50 apparently monocular cells showed any evidence of remaining, subliminal excitatory input from the “silent” eye when the two eyes were stimulated with gratings of similar orientation, and even among the small proportion of cells that remained binocularly driven, very few exhibited facilitation when stimulated binocularly. The majority of cells from both exotropes and esotropes, even those that could be independently driven through either eye, displayed nonspecific interocular suppression: stimulation of the nondominant eye with a drifting grating of any orientation depressed the response to an optimal grating being presented to the dominant eye. This phenomenon exhibited a gross nonlinearity in that it was dependent on the temporal sequence of stimulus presentation: stimulation of the nondominant eye caused significant suppression only if the neuron was already responding to an appropriate stimulus in the dominant eye, but not when onset of stimulation in the two eyes was simultaneous. Interocular suppression was always independent of the relative spatial phase of the two grating stimuli, and usually broadly tuned for the spatial frequency of the suppressive stimulus. Suppression may depend on inhibitory interaction between neighboring ocular dominance columns, combined with the loss of conventional disparity-selective binocular interactions for matched stimuli in the two eyes. The similarity of interocular suppression in strabismic cats and that caused by orthogonal gratings in the two eyes in normal cats (Sengpiel and Blakemore, 1994; Sengpiel et al., 1994) suggests that strabismic suppression and binocular rivalry depend on similar neural mechanisms.
Aplysia cell adhesion molecules and serotonin regulate sensory cell- motor cell interactions during early stages of synapse formation in vitro
Authors: Zhu H , Wu F , Schacher S
Published: April 2018

Long-term facilitation of sensorimotor synapses of Aplysia in culture by serotonin (5-HT) is accompanied by two changes: an increase in the number of sensory cell branches and varicosities contacting the major axons of the target motor cell L7, and a downregulation of Aplysia cell adhesion molecules (apCAM) from the surface of the presynaptic sensory cell. We tested the hypothesis that the two changes may be linked; the 5-HT-induced decrease of apCAM levels from sensory neurites may defasciculate sensory neurites from each other and make the surface of the motor axons a more attractive substrate for new growth and synapses. We used developing cultures to examine the relationship of neuritic branching, varicosity formation, and efficacy of the connections formed by sensory cells to levels of apCAM expression on the motor cell. We then determined the consequences of 5-HT applied during the early period of interaction between sensory and motor cells (day 1 or 2 in culture) on the pattern of sensory cell growth and synapse formation. We report that the number of sensory cell branches and varicosities, and the ability of sensory growth cones to fasciculate with L7 axons and form chemical connections correlate with the level of apCAM expression on different regions of L7. Early exposure to 5-HT increased the number of sensory cell branches and varicosities contacting newly regenerated distal neurites of L7 to levels that would normally occur when the sensory neurites interact with the major proximal axons of L7. Treatment with 5-HT also modulated the efficacy of the developing synaptic connections. The change in synapse efficacy was accompanied by an increase in the formation of new sensory varicosities and branches with pioneering growth cones extending on the major axons of L7. The results are consistent with the hypothesis that treatment with 5-HT modulates local differences in the expression of cell adhesion molecules on the surface of the interacting cells making motor neurites more attractive for sensory growth cones, thereby affecting new sensory neuritic growth and synapse formation.
Synaptic-type acetylcholine receptors raise intracellular calcium levels in neurons by two mechanisms
Authors: Rathouz MM , Berg DK
Published: April 2018

Nicotinic acetylcholine receptors (AChRs) located in the postsynaptic membrane on neurons are responsible for mediating fast, excitatory synaptic transmission. If synaptic AChRs are also highly permeable to calcium as reported recently for several kinds of neuronal AChRs, the synaptic receptors could regulate calcium-dependent events in the neurons in concert with normal transmission. Chick ciliary ganglion neurons have two classes of AChRs, one located predominantly in the synaptic membrane and responsible for synaptic signaling through the ganglion and the other located almost exclusively in nonsynaptic membrane and having no known function. The nonsynaptic receptors can readily elevate intracellular calcium concentrations. The experiments reported here indicate that synaptic-type receptors can raise intracellular calcium levels to the same extent as the nonsynaptic receptors and that they do so not only by being permeable to calcium themselves but also by activating voltage-dependent calcium channels (VDCCs). Currents of equivalent amplitude are obtained through the synaptic-type receptors when neurons are bathed in solutions containing either sodium or calcium as the sole extracellular cation. Measuring the effect of ion substitutions on the reversal potential of the receptors and applying the Goldman-Hodgkin-Katz constant field equation indicates the receptors are at least as permeable to calcium as to sodium. When neurons are loaded with the calcium-sensitive dye fluo-3 and challenged with nicotine, both the synaptic-type and nonsynaptic AChRs substantially elevate intracellular calcium levels under physiological conditions, and do so largely by activating VDCCs. Confirmation that synaptic-type AChRs can elevate intracellular calcium levels in the absence of contributions from VDCCs was obtained from voltage-clamp experiments on neurons loaded with fluo-3. The fluorescence signals indicate that the nicotine-induced calcium increases in neurons voltage clamped at rest are nearly as great as those induced in the same neurons when VDCCs are maximally activated by a voltage step. Calcium flux through AChRs may be particularly important for mediating local changes in calcium concentrations near the plasma membrane, which, in turn, could regulate specific membrane- associated calcium-dependent events.
Activity-dependent structural dynamics of insect sensory fibers
Authors: Pfluger HJ , Hurdelbrink S , Czjzek A , Burrows M
Published: April 2018

This report analyses the role of neuronal activity in shaping the axonal arborizations of sensory neurons from individually identified filiform hairs on the prosternum of locusts (Locusta migratoria), and their connections with a pair of identified interneurons (A4I1). Afferents from lateral filiform hairs terminate in the ipsilateral neuropil and connect only with the ipsilateral interneuron in all instars. Afferents from ventral filiform hairs possesses ipsi- and contralateral branches and make monosynaptic connections with both interneurons in first instars. In later instars, the ipsilateral branch, and its synaptic connection to the ipsilateral interneuron, is gradually reduced until it is lost in the adult, whereas the contralateral branch, and its synaptic connection with the contralateral interneuron, is strengthened. Therefore, after an initial overgrowth of fibers and synapses, segregation of fibers occurs involving the loss of synaptic connections. This loss of branches and synapses was prevented by immobilizing a subpopulation of ventral and lateral filiform hairs, or each group independently, so that their normal activity was blocked. In such treated animals afferents from ventral filiform hairs retain their ipsi- and contralateral branches until adulthood. We therefore conclude that afferent activity plays an important role in shaping the final structure and connectivity of afferents, as neither the peripheral position of the receptors nor the hormonal environment was changed by these manipulations.
Characterization of neural cell adhesion sites: point contacts are the sites of interaction between integrins and the cytoskeleton in PC12 cells
Authors: Arregui CO , Carbonetto S , McKerracher L
Published: April 2018

As developing or regenerating neurons grow, their axons seek cues in the extracellular matrix that are recognized by integrin receptors. To understand the regulation and structure of neural integrin complexes, we have examined the association of two functionally important integrins, alpha 1 beta 1 and alpha 3 beta 1, within PC12 cells. Detergent-resistant cytoskeletal ghosts were prepared from PC12 cells and examined by immunoblotting. In cells maintained in suspension the alpha 1, alpha 3, and beta 1 integrin subunits were solubilized by Triton X-100 detergent. In contrast, when cells were grown on collagen or laminin about 50% of the alpha 1 and beta 1 subunits were retained with the cytoskeleton, but alpha 3 remained soluble. Confocal immunofluorescence microscopy of whole cells demonstrated that all three integrin subunits were expressed in a punctate pattern on the cell surface in point contacts. Point contacts were also found to be the predominant adhesion structure of dorsal root ganglion neurons. After detergent extraction of PC12 cells, the point contacts remained only at the cell-substrate interface. Vinculin, which is found consistently in focal contacts on non-neural cells, showed only a partial colocalization with the point contacts, being expressed mainly at the tips of filopodia and the periphery of cell bodies. Talin showed no obvious codistribution with beta 1 integrin immunoreactivity in point contacts. Immunoreactivity to p125FAK was not detected in PC12 cells, although astrocytes, which have both focal contacts and point contacts have p125FAK only at focal contacts. These observations, together with previous data (Turner et al., 1989; Tawil et al., 1993), suggest that point contacts are functional adhesion sites and are structurally distinct from focal contacts found in non-neuronal cells.
Retinal axon divergence in the optic chiasm: dynamics of growth cone behavior at the midline [published erratum appears in J Neurosci 1995 Mar;15(3):following table of contents]
Authors: Godement P , Wang LC , Mason CA
Published: April 2018

To study how retinal ganglion cell axons diverge in the optic chiasm, the behavior of dye-labeled fibers was monitored in real time with video microscopy in an isolated preparation of embryonic mouse brain, with a focus on embryonic day 15–16. These real-time studies have revealed the dynamics of the growth of individual retinal axons, especially the tempo of extension and growth cone behaviors during divergence in the chiasm, a model for “decision” regions in developing pathways. Within the chiasm, retinal growth cones extend by saltatory growth, consisting of bursts of rapid advance alternating with pauses in extension. During pauses, growth cone appendages remain motile, and develop asymmetries prior to a change in the axis of growth. In a zone straddling the midline, retinal fibers, irrespective of destination, display long pauses for up to several hours, making small advances and retractions with no net extension. While crossed fibers ultimately progress through the midline, uncrossed fibers from inferior temporal retina develop wide-ranging branched growth cones, and then turn back to the ipsilateral side. Turns are effected by the selective retraction or micropruning of asymmetric foci of motile activity, and by the transformation of a backward-directed filopodium into a new growth cone. The behavior of retinal axons at the midline supports the hypothesis that this locus contains cues important for retinal axon divergence. Moreover, the observations of growth cone kinetics in the chiasm elucidate which growth cone forms seen in static preparations mediate growth cone turning, and suggest a model of axon navigation in decision regions in the intact nervous system.
Assembly of GABAA receptor subunits: role of the delta subunit
Authors: Saxena NC , Macdonald RL
Published: April 2018

GABAA receptor channels (GABARs) composed of different combinations of rat alpha 1, beta 1, gamma 2L, and delta subunits were expressed transiently in mouse fibroblast cells (L929 cells). Whole-cell recordings were obtained from transfected cells to determine which combinations of GABAR subunits formed functional receptor channels, and to compare the electrophysiological and pharmacological characteristics of GABAR channels expressed in the presence and absence of the delta subunit. Only alpha 1 beta 1 gamma 2L, alpha 1 beta 1 gamma 2L delta, and alpha 1 beta 1 delta subunit combinations assembled to form functional GABAR channels and the presence of the delta-subunit slowed the rate of acute desensitization of GABA-evoked current during GABA application and the rate of recovery of GABA-evoked current following GABA application. These three different GABAR channel isoforms also showed distinct pharmacological profiles with differential sensitivity to block by zinc. Zinc was a potent blocker of alpha 1 beta 1 delta GABAR channels, a moderate-strength blocker of alpha 1 beta 1 gamma 2L delta GABAR channels, and did not block the alpha 1 beta 1 gamma 2L GABAR channels. These findings suggest that GABAR isoforms containing the delta subunit constitute a novel GABAR channel with distinct electrophysiological and pharmacological characteristics.
Vasoactive intestinal peptide stimulates neuropeptide Y gene expression and causes neurite extension in PC12 cells through independent mechanisms
Authors: Colbert RA , Balbi D , Johnson A , Bailey JA , Allen JM
Published: April 2018

Vasoactive intestinal peptide (VIP) is widely recognized as a regulator of tyrosine hydroxylase via a mechanism of trans-synaptic activation. Subsets of adrenal medullary cells and postganglionic sympathetic nerves coexpress the peptide neurotransmitter neuropeptide Y (NPY) with catecholamines. Using PC12 cells transiently expressing a fusion gene in which the bacterial enzyme chloramphenicol acetyltransferase (CAT) is under the control of 700 base pairs of the 5′ flanking region of the NPY gene, we have studied the role of VIP and the related peptide pituitary adenylate cyclase activating peptide (PACAP) in regulating NPY gene transcription. Both VIP and PACAP stimulated expression of the NPY gene through activation of cAMP-dependent protein kinase. PACAP was 1000-fold more potent in eliciting this response compared to VIP and activity resided in its N-terminal 27 amino acids. Both VIP and PACAP caused a subpopulation (approximately 50%) of PC12 cells to undergo profound morphological changes in that the cells extended long, slender neurites with prominent growth cones. This change in morphology was unaffected by preincubating cells with inhibitors of either cAMP- dependent protein kinase or calcium/phospholipid-dependent protein kinase. A trophic role for either VIP or PACAP in regulating sympathetic nerve function is proposed.
Skilled reaching deficits in unilateral dopamine-depleted rats: impairments in movement and posture and compensatory adjustments
Authors: Miklyaeva EI , Castaneda E , Whishaw IQ
Published: April 2018

Rats receiving unilateral dopamine (DA) depletions have bilateral deficits in using the forelimbs for skilled reaching. These impairments were investigated using end-point, video, and kinematic measures. Control rats and groups of rats with > 98% unilateral depletions (confirmed by tissue, apomorphine, and amphetamine assay), produced by 6-hydroxydopamine (6-OHDA) injected into the nigrostriatal bundle, were tested for 100 d on two reaching tasks. One depleted group used the contralateral-to-lesion (bad), and the other the ipsilateral-to-lesion (good), limb. Rats using their bad limb made few successful reaches and had dysfunctions in aiming, pronating, and supinating, and in using the digits to grasp and release food. Rats using the good limb were initially impaired, but improved, and could make these movements. Neither depleted group was able to use their bad limbs to assist actively the postural changes required for reaching. Thus, they did not use the diagonal supporting pattern (the nonreaching forelimb and diagonal hind limb) from which control rats initiated reaching. The group using their bad limb initiated reaching from a base of support distributed on the ipsilateral-to-lesion limbs, while the group using their good limb initiated reaching from a base of support centered on the ipsilateral rear limb. The impairments in making voluntary movements and postural adjustments with the bad limbs and the behavioral changes introduced by the compensatory dependency on good limbs account for the bilateral deficits in skilled movements. The results show that DA is required for skilled movements and postural adjustments and demonstrate that behavioral compensation can contribute to recovery.
The L2/HNK-1 carbohydrate is preferentially expressed by previously motor axon-associated Schwann cells in reinnervated peripheral nerves
Authors: Martini R , Schachner M , Brushart TM
Published: April 2018

The carbohydrate epitope L2/HNK-1 (hereafter designated L2) is expressed in the adult mouse by myelinating Schwann cells of ventral roots and muscle nerves, but rarely by those of dorsal roots or cutaneous nerves. Since substrate-coated L2 glycolipids promote outgrowth of cultured motor but not sensory neurons, L2 may thus influence the preferential reinnervation of muscle nerves by regenerating motor axons in vivo. In the present study, we have analyzed the influence of regenerating axons on L2 expression by reinnervated Schwann cells by directing motor or sensory axons into the muscle and cutaneous branches of femoral nerves of 8-week-old mice. We observed that regenerating axons from cutaneous branches did not lead to immunocytochemically detectable L2 expression in muscle or cutaneous nerve branches. Axons regenerating from muscle branches led to a weak L2 expression by few Schwann cells of the cutaneous branch, but provoked a strong L2 expression by many Schwann cells of the muscle branch. Myelinating Schwann cells previously associated with motor axons thus differed from previously sensory axon-associated myelinating Schwann cells in their ability to express L2 when contacted by motor axons. This upregulation of L2 expression during critical stages of reinnervation may provide motor axons regenerating into the appropriate, muscle pathways with an advantage over those regenerating into the inappropriate, sensory pathways.
Hepatocyte growth factor is a mitogen for Schwann cells and is present in neurofibromas
Authors: Krasnoselsky A , Massay MJ , DeFrances MC , Michalopoulos G , Zarnegar R , Ratner N
Published: April 2018

To characterize mitogens that might contribute to Schwann cell proliferation during development or in tumors, we tested the ability of hepatocyte growth factor (HGF) to stimulate Schwann cell division in vitro. HGF is a potent mitogen for purified rat Schwann cells; DNA synthesis in rat Schwann cells was stimulated 20–40-fold by 3–10 ng/ml HGF. Rat Schwann cells express c-met mRNA, encoding the HGF receptor, but not HGF mRNA, implying that HGF might act as a paracrine Schwann cell growth factor. HGF-stimulated Schwann cell proliferation differs from that of previously described Schwann cell mitogens in that its activity is abolished by forskolin and is not inhibited or potentiated by addition of transforming growth factor beta (TGF beta) or fibroblast growth factor (FGF). HGF is probably not a component of the axonal signal thought to cause Schwann cell division during development, as anti-HGF neutralizing antibodies failed to block neuron-stimulated Schwann cell proliferation. In contrast, mitogenic activity present in normal human adult nerves and in neurofibromas from patients with type 1 neurofibromatosis analyzed in the absence of forskolin is largely inhibitable by anti-HGF. Thus, HGF is a novel mitogen for Schwann cells in vitro and it is present in Schwann cell tumors, suggesting a potential role for HGF after wounding of peripheral nerves or in tumor growth.
Comparison of spatial firing characteristics of units in dorsal and ventral hippocampus of the rat
Authors: Jung MW , Wiener SI , McNaughton BL
Published: April 2018

The septal and temporal poles of the hippocampus differ markedly in their anatomical and neurochemical organization. Although it is well established that the internal representation of space is a fundamental function of hippocampal neurons, most of what is known about spatial coding in the hippocampus of freely moving animals has come from recordings from the dorsal one-third (largely for technical convenience). The present study therefore compared the spatial selectivity of CA1 neurons in the dorsal and ventral hippocampi of rats during performance of a food reinforced, random search task in a square chamber containing simple visual landmarks. Neural activity was recorded in the dorsal and ventral hippocampi of opposite hemispheres in the same rats, in many cases simultaneously. As in dorsal hippocampus, ventral CA1 units could be classified as “complex spike” (pyramidal) cells or “theta” interneurons. Both dorsal and ventral theta cells fired at relatively high rates and with low spatial selectivity in the apparatus. Of the population of complex spike cells in the ventral hippocampus, a significantly smaller number had “place fields” than in the dorsal hippocampus, and the average spatial selectivity was of significantly lower resolution than that found among dorsal hippocampal complex spike cells. Thus, a septotemporal difference of spatial selectivity was found in the CA1 field of the rat hippocampus, complementing many other anatomical and neuropharmacological studies. A number of possible functional interpretations can be suggested from these results, including a computational advantage of representing space at different scales or a preeminence of essentially nonspatial information processing in the ventral hippocampus.
Transparent motion perception as detection of unbalanced motion signals. I. Psychophysics
Authors: Qian N , Andersen RA , Adelson EH
Published: April 2018

Our visual system can solve the difficult problem of representing multiple motions in the same part of the visual space, the motion transparency problem. We investigated the conditions under which transparent motion perception occurs through psychophysical observations, using a series of visual displays composed of two simple patterns moving in opposite directions. We found that whenever a display has finely balanced opposing motion signals in all local regions, it is perceptually nontransparent. The displays that appeared transparent always contain locally unbalanced motion signals, with some local regions having net motion signals in one direction and some other regions in the opposite direction. These interdigitating net motion signals in both directions appear to be integrated separately to form two overlapping transparent surfaces. Displays that were spatially balanced could be made perceptually transparent if the two components moving in opposite directions were at different stereo depth planes or had different spatial frequency contents. Our results can be explained by proposing a disparity- and spatial frequency-specific suppression stage in the motion pathway, at which motion signals of different directions, but of the same disparity and spatial frequency contents, locally inhibit each other. Such a mechanism would suppress noise input to the motion system, which generally activates several direction channels simultaneously, and would still not eliminate activity evoked by transparent surfaces that are at different depths or have different textures.
Transparent motion perception as detection of unbalanced motion signals. II. Physiology
Authors: Qian N , Andersen RA
Published: April 2018

We investigated how the primate visual system solves the difficult problem of representing multiple motion vectors in the same part of the visual space--the problem of motion transparency. In the preceding companion article we reported that displays with locally well-balanced motion signals in opposite directions are perceptually nontransparent (i.e., one does not see two coherent moving surfaces) and that transparent displays always contain locally unbalanced motion signals. This is exemplified by our paired and unpaired dot patterns. Although both types of stimuli contain two sets of dots moving in opposite directions, the former is locally well balanced and appears like flicker while the latter gives a perception of two transparent surfaces. In this article we report our physiological recordings from areas V1 and MT of behaving monkeys, comparing single-cell responses to the paired and the unpaired dot patterns. Although a small proportion of directionally selective V1 cells responded differently to the two types of patterns, the average V1 responses could not reliably distinguish between the paired and the unpaired stimuli. A large fraction of MT cells, on the other hand, responded significantly better to the unpaired dot patterns than to the paired ones. Furthermore, the average response of all MT cells to the unpaired dot patterns was significantly higher than that to the paired dot patterns. These results demonstrate a neural correlate of the perceptual transparency at the level of MT. On the other hand, V1 cells do not generally discriminate between the transparent and nontransparent stimuli, indicating that V1 activity is not well correlated with the perception of motion transparency. Our results are consistent with a two-stage model for motion processing: the first stage measures local motion and the second stage introduces suppression if different directions of motion are present at a local region of the visual field. The first stage is located primarily in V1 and the second stage primarily in MT. Finally, we found a strong and negative correlation between the degree of the opponent-direction suppression of MT cells and their responses to flicker noise stimuli. This result suggests that one of the fundamental roles of the opponent-direction suppression in MT is noise reduction.
Ocular dominance column development: strabismus changes the spacing of adjacent columns in cat visual cortex
Authors: Lowel S
Published: April 2018

To investigate the role of visual experience for the gross layout of ocular dominance (OD) columns in the visual cortex, I compared the respective patterns in normally raised and strabismic cats. OD domains were visualized by (1) transneuronal labeling of the afferents from the left or right eye with intraocular 3H-proline injections or (2) 14C-2- deoxyglucose autoradiography after monocular visual stimulation in awake animals. To obtain the complete pattern of OD columns, flat-mount sections were prepared from the unfolded cortical hemispheres. Eliminating correlated activity between the two eyes by making the animals strabismic influenced the gross layout of the OD domains. In area 17, OD domains become more sharply delineated than in normal animals and spaced more widely. Spatial frequency analyses revealed a mean spacing of adjacent columns of 1100–1300 microns in strabismic and of 800–1000 microns in normal cats. In area 18, the spacing of the ocular dominance domains is larger than in area 17 for both normal and strabismic cats (1500–1650 microns), but little influenced by strabismus. These results indicate that in area 17 decreased correlation of activity between the eyes alters the periodicity of OD columns. In addition, these observations suggest that not only the segregation of afferents into distinct columns but also the final expression of the columnar grid is influenced by visual experience, and in particular by the temporal patterning of neural activity. This is further evidence for the hypothesis that the development of OD columns is governed by activity-dependent self-organizing principles.
Disruption of microfilaments in growth cones following depolarization and calcium influx
Authors: Neely MD , Gesemann M
Published: April 2018

Depolarization of leech neurons growing on extracellular matrix extract (ECM) leads to cessation of neurite outgrowth, rounding up of the peripheral regions of the growth cone, loss of filopodia, and neurite retraction. These responses depend on the influx of calcium (Neely, 1993). The aim of the present experiments was to analyze how the cytoskeleton becomes reorganized as growth cones change their morphology. Immunocytochemistry revealed a loss of microfilaments in the tips of neurites growing on ECM after depolarization. Leech neurons cultured on a different substrate, the plant lectin concanavalin A (ConA), continue to grow during and after depolarization (Grumbacher- Reinert and Nicholls, 1992; Neely, 1993). As expected, we did not observe any change in the distribution of microfilaments after depolarization on ConA. Since there is evidence that this lack of response is due to a reduced calcium influx during depolarization of neurons on ConA (Ross et al., 1988), the effect of the calcium ionophore A23187 on the outgrowth of these cells was analyzed. In the absence of depolarization, this ionophore caused cessation of growth cone motility and a loss of microfilaments, while microtubules were not affected. Cytochalasin D, a microfilament-disrupting agent, induced changes in growth cone morphology and neurite retraction similar to those observed after depolarization and calcium influx. Application of phalloidin, a drug that stabilizes microfilaments, inhibited depolarization-induced retraction of neurites on ECM. By contrast, stabilization of microtubules with taxol did not prevent depolarization from inducing changes in growth cone morphology and neurite growth. These experiments show that changes in growth cone morphology and motility of leech neurons induced by depolarization and calcium influx are accompanied by a dramatic change in the organization of microfilaments, but not microtubules.
ATP mediates fast synaptic potentials in enteric neurons
Authors: Galligan JJ , Bertrand PP
Published: April 2018

Conventional intracellular electrophysiological methods were used to study fast synaptic transmission in the myenteric plexus of guinea pig ileum in vitro. Fast excitatory postsynaptic potentials (fEPSPs) were evoked in 98 neurons following single stimuli applied to interganglionic connectives. The nicotinic antagonist hexamethonium (100 microM) reduced fEPSPs by 83% in 37 neurons; these fEPSPs were considered to be cholinergic. In 61 neurons, hexamethonium reduced fEPSPs by 33%; fEPSPs recorded in the presence of hexamethonium were considered to be noncholinergic. Similar data were obtained using the nicotinic antagonist mecamylamine (10 microM) to block fEPSPs. Hexamethonium or mecamylamine completely blocked depolarizations caused by acetylcholine (ACh) applied by ionophoresis. The P2 receptor antagonist suramin (1–300 microM) inhibited noncholinergic fEPSPs in 30 cells; the suramin IC50 was 4 microM. Suramin (100 microM) did not block depolarizations caused by ACh or 5-HT, but suramin blocked depolarizations caused by ATP. Hexamethonium did not block ATP-induced depolarizations. The estimated reversal potential for suramin-sensitive fEPSPs and ATP-induced depolarizations was -25 and -16 mV, respectively. ATP responses were reduced in low-sodium (26 mM) extracellular solution, suggesting that ATP activates a cation channel. These data indicate that in myenteric nerves ATP, in addition to ACh, contributes to fast synaptic transmission.
Direct measurement of brain temperature during and after intraischemic hypothermia: correlation with behavioral, physiological, and histological endpoints
Authors: Nurse S , Corbett D
Published: April 2018

The aim of the present study was to evaluate critically the protection afforded by hypothermia against ischemic injury to the hippocampus. Hypothermic treatment was applied selectively to the brain during a 5 min carotid artery occlusion in gerbils. Following a period of recovery, two independent measures were used to assess hippocampal function: (1) an open field test of spatial memory (assessment was made during the first 10 d after ischemia) and (2) measurement of evoked potentials from area CA1 in hippocampal slices (3 weeks after the ischemic episode). The functional outcome portrayed by these tests was compared to a morphological evaluation of CA1 pyramidal cells at three rostrocaudal levels. All evaluations were carried out in the same animals. We found converging evidence that intraischemic hypothermia provides virtually complete protection against a 5 min episode of cerebral ischemia. Animals treated with hypothermia performed as well as sham-operated controls in a spatial memory task, had field potentials that were indistinguishable from normal animals and CA1 cells appeared normal when assessed histologically. In contrast, ischemia at normothermia resulted in a deficit in open field behavior (p < 0.01), diminished field potentials in stratum radiatum (p < 0.01), and near total loss of pyramidal cells in dorsal CA1 (p < 0.01). There was a remarkably high correlation between these diverse measures (r ranged from 0.7 to 0.9, p < 0.01), which provides strong support for the use of hypothermia as an effective treatment for ischemia. This study introduces a novel approach for the evaluation of putative anti- ischemic treatments: combining behavioral, electrophysiological, and histological measures.(ABSTRACT TRUNCATED AT 250 WORDS)
A comparison of nucleus accumbens neuronal firing patterns during cocaine self-administration and water reinforcement in rats
Authors: Carelli RM , Deadwyler SA
Published: April 2018

The firing patterns of nucleus accumbens (NA) neurons in the rat were recorded during cocaine self-administration and responding for water. Recordings were obtained from permanently implanted multiple-electrode arrays (eight microwires) inserted bilaterally into rostral portions of the NA in subjects (n = 18) exhibiting stable cocaine self- administration (0.33 mg/infusion), and during stable responding for water reinforcement. Electronically isolated and identified NA neurons exhibited four distinct patterns of phasic activity relative to the reinforced response. Three of these firing patterns were observed during both cocaine self-administration and water reinforcement sessions. Response-related activity was categorized by cells that showed an anticipatory increase in firing rate during the preresponse phase (type PR), and by cells that were excited (type RFE) or inhibited (type RFI) following the response in the reinforcement phase. PR and RFE cells showed significantly reduced peak firing during cocaine self- administration, compared to similar cells in water reinforcement sessions. A fourth type of NA firing pattern (type PR+RF) was observed only in cells recorded during cocaine self-administration sessions (Carelli et al., 1993b). PR+RF neurons exhibited two distinct peaks, one preceding the response and terminating at response completion (like PR cells), and a second peak immediately following the response (like RFE cells) with an inhibitory period between the two peaks (like RFI cells). The findings are discussed in terms of the role of the NA in mediating the reinforcing properties of both cocaine and water.
Morphological analysis of dendritic spine development in primary cultures of hippocampal neurons
Authors: Papa M , Bundman MC , Greenberger V , Segal M
Published: April 2018

We monitored developmental alterations in the morphology of dendritic spines in primary cultures of hippocampal neurons using confocal laser scanning microscopy (CLSM) and the fluorescent marker Dil. Dissociated rat hippocampal neurons were plated on polylysine-coated glass cover slips and grown in culture for 1–4 weeks. Fixed cultures were stained with Dil and visualized with the CLSM. Spine density, spine length, and diameters of spine heads and necks were measured. Some cultures were immunostained for synaptophysin and others prepared for EM analysis. In the 1–3 week cultures, 92–95% of the neurons contained spiny dendrites. Two subpopulations of spine morphologies were distinguished. At 1 week in culture, “headless” spines constituted 50% of the spine population and were equal in length to the spines with heads. At 2, 3, and 4 weeks in culture headless spines constituted a progressively smaller fraction of the population and were, on average, shorter than spines with heads. Spines with heads had narrower necks than headless spines. At 3 weeks in culture, spines were associated with synaptophysin-immunoreactive labeling, resembling synaptic terminals. At 4 weeks in culture, only 70% of the Dil-filled cells had spiny dendrites, and the density of spines decreased. Ultrastructurally, the majority of dendritic spine- like structures at 1 week resembled long filopodia without synaptic contacts. The majority of axospinous synapses were on short “stubby” spines. At 3 weeks in culture, the spines were characteristic of those seen in vivo. They contained no microtubules or polyribosomes, were filled with a characteristic, filamentous material, and formed asymmetric synapses. These studies provide the basis for further analysis of the rules governing the formation, development, and plasticity of dendritic spines under controlled, in vitro conditions.
Adoption reverses the long-term impairment in glucocorticoid feedback induced by prenatal stress
Authors: Maccari S , Piazza PV , Kabbaj M , Barbazanges A , Simon H , Le Moal M
Published: April 2018

The development of the organism is subjected to critical and complex influences during the perinatal period. Prenatal and postnatal stresses can have different long-term behavioral effects, and appropriate postnatal manipulations can counteract the behavioral effects of prenatal stress. In the present study, we investigated the involvement of changes in the activity of the hypothalamo-pituitary-adrenal (HPA) axis in the long-term effects of prenatal and postnatal events and of interactions between them. We investigated stress-induced corticosterone secretion and hippocampal corticosteroid receptors in male adult rats submitted to prenatal and/or postnatal manipulations. Repeated restraint during the last week of pregnancy was used as prenatal stressor, and adoption at birth was used to change the postnatal environment. We found that (1) prenatal stress prolongs stress-induced corticosterone secretion in adult rats, which was attributed to the observed decrease in central corticosteroid receptors; (2) adoption, irrespective of the stress experience of the foster mother, reverses the effects of prenatal stress; and (3) adoption per se increases maternal behavior and decreases the stress- induced corticosterone secretion peak in the adult offspring. In conclusion, certain prenatal and postnatal manipulations appear to have opposite long-term effects on the activity of the HPA axis, and adoption, probably by modifying maternal behavior, can protect against the effects of prenatal stress. Thus, changes in the activity of the HPA axis may be one of the biological substrates of the long-term effects of certain perinatal events.