bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal and psychophysical sensitivity to motion signals in extrastriate area MST of the macaque monkey
Authors: Celebrini S , Newsome WT
Published: April 2018

We recorded the responses of single neurons in extrastriate area MST while rhesus monkeys discriminated the direction of motion in a set of stochastic visual displays. By varying systematically the strength of a coherent motion signal within the visual display, we were able to measure simultaneously the monkeys' psychophysical thresholds for direction discrimination and the responses of single neurons to the same motion signals. Neuronal thresholds for reliably signaling the direction of motion in the visual display were calculated from the measured responses using a method based in signal detection theory. Neurons in MST were exquisitely sensitive to motion signals in the display, having thresholds for discriminating the direction of coherent motion that were, on average, equal to the psychophysical thresholds of the monkeys. For many MST neurons, the intensity of the response was correlated with the monkey's psychophysical judgements for repeated presentations of a given near-threshold stimulus; the monkey tended to choose the preferred direction of the neuron under study when that neuron responded more strongly to the stimulus. In both of these respects, MST neurons were indistinguishable from neurons in extrastriate area MT, a major source of afferent input to MST. In a second set of experiments, we found that both of these results held true in the face of pronounced manipulations of the visual stimulus. Severe reductions in stimulus size and speed, for example, compromised neuronal and psychophysical sensitivities by similar amounts so that the average neuronal and psychophysical thresholds remained approximately equal. In addition, the trial-to-trial covariation of neuronal response and perceptual decision was unaffected by our stimulus manipulations. Thus, MST neurons carry signals appropriate for supporting psychophysical performance on our task over an impressively wide range of stimulus configurations.
Drug- and behavior-associated changes in dopamine-related electrochemical signals during intravenous cocaine self-administration in rats
Authors: Gratton A , Wise RA
Published: April 2018

High-speed chronoamperometry was used to determine the moment-to-moment and day-to-day changes in dopamine-related electrochemical signals in the nucleus accumbens of rats allowed to self-administer cocaine (0.8 mg/kg/injection) intravenously. The first, unexpected, cocaine injection caused an abrupt and long-lasting decrease in electrochemical signal. The second and subsequent injections caused shorter decreases in signal that were followed, beginning 2–3 min after injection, with a return of signal toward the preinjection baseline. Thus, the signal increased just prior to each lever press, peaked at the moment of lever pressing, and decreased for some minutes after each response. Over the first testing session, the phasic fluctuations kept the signal somewhat below the preinjection baseline. On the second and subsequent days, there were large increases in signal following presentation of the light stimulus that marked the onset of drug availability and that was paired with each cocaine injection; this light stimulus had no effect on the first day, prior to drug-light pairings. The first injection of the second and subsequent days caused an additional increase in signal; the magnitude of the increase was comparable to that caused by the initial stimulus, and the two increases summated to elevate voltammetric signals well above the normal baseline. Subsequent injections caused immediate but short-lived decreases in signal, as were seen on the first day; again, the signal returned to or rose slightly above the preinjection level by the time of the next lever press and injection. No decrease was seen after lever presses when earned injections were occasionally withheld; rather, the signal continued to increase slowly until another lever press was made and a subsequent injection was received. When access to the lever was blocked and the infusion pump was inactivated at the end of self-administration sessions, the animals became agitated and the electrochemical signal increased and remained elevated for 20–40 min before gradually declining toward the original baseline. Thus, the effects of cocaine on DA-associated signals in nucleus accumbens (1) changed dramatically during the development of the self-administration habit and (2) depended on environmental and behavioral as well as pharmacological factors. In trained animals, cocaine self-administration was accompanied by a tonic elevation of DA-associated signals and by phasic fluctuations time-locked to each cocaine injection.
Transforming growth factor alpha (TGF alpha) expression in degenerating motoneurons of the murine mutant wobbler: a neuronal signal for astrogliosis?
Authors: Junier MP , Coulpier M , Le Forestier N , Cadusseau J , Suzuki F , Peschanski M , Dreyfus PA
Published: April 2018

The enhanced expression of the trophic factor transforming growth factor alpha (TGF alpha) in reactive astrocytes following CNS injury suggests that TGF alpha has a role in the development of astrogliosis. We explored this hypothesis in the murine mutant wobbler, which presents a progressive motoneuronal degeneration associated with an astrogliosis. Evolution of astrogliosis, and expression of TGF alpha precursor (pro-TGF alpha) and of its receptor were examined over the course of the disease, using genetically diagnosed animals and immunocytochemical techniques. We report here that degenerating motoneurons of the cervical spinal cord and a subset of astrocytes express pro-TGF alpha, prior to the onset of astrogliosis, when the first clinical manifestations of the disease are observed at 4 weeks of age. TGF alpha expression appeared strongly correlated with motoneuronal degeneration. All pro-TGF alpha-immunoreactive neurons exhibited a degenerative morphology, and the number of pro-TGF alpha- immunoreactive neurons increased with the progression of the disease. At the glial level, we observed that astrogliosis was a transitory phenomenon in the wobbler mice, developing in coordination with the motoneuronal expression of pro-TGF alpha. Astrogliosis became evident in 6-week-old wobbler mice, when the number of pro-TGF alpha- immunoreactive motoneurons was maximal, and regressed in older mutant mice in correlation with the disappearance of pro-TGF alpha- immunoreactive motoneurons. Furthermore, TGF alpha/EGF receptor immunoreactivity was exclusively localized in a subset of reactive astrocytes, its expression following closely the course of the astrogliosis. These data show that TGF alpha synthesis by the affected motoneurons is an early event in the course of the wobbler disease, and suggest a role for TGF alpha as a neuronal inducer of astrocytic reactivity.
Calcium dependence of hypoosmotically induced potassium release in cultured astrocytes
Authors: Bender AS , Norenberg MD
Published: April 2018

A major mechanism in cell volume regulation after hypoosmotic stress is K+ release. Our studies show that in astrocytes, K+ release during hypoosmotic stress is a Ca(2+)-dependent process. Agents that increase intracellular Ca2+, such as ionomycin and ouabain, potentiated hypoosmotically stimulated K+ release, while compounds that block Ca2+ entry during hypoosmotic stress, such as nimodipine, bepridil, and MK- 801, inhibited hypoosmotically stimulated K+ release. Similarly, chelation of intracellular Ca2+ blocked hypoosmotically induced K+ release. Caffeine and U-73122 also inhibited K+ efflux under hypoosmotic conditions, suggesting that intracellular Ca2+ release from Ca(2+)-induced Ca2+ release stores and inositol trisphosphate-sensitive intracellular Ca2+ stores play a role in the mechanism of K+ release. Blocking the activity of calmodulin, and of CaM kinase, attenuated hypoosmotically induced K+ release. Our findings indicate that entry of extracellular Ca2+ and Ca2+ release from intracellular stores play a key role in the activation of K+ release under hypoosmotic conditions and thus in cell volume regulation.
The consistency, extent, and locations of early-onset changes in cortical nerve dominance aggregates following injury of nerves to primate hands
Authors: Kolarik RC , Rasey SK , Wall JT
Published: April 2018

The somatosensory cortex of primates contains patch- and bandlike aggregates of neurons that are dominantly activated by cutaneous inputs from the radial, median, and ulnar nerves to the hand. In the present study, the area 3b hand cortex of adult monkeys was mapped immediately before and after combined median and ulnar nerve transection to evaluate the consistency, extent, and location of early post-injury alterations in the deprived median and ulnar nerve cortical bands. Several alterations were observed acutely after injury. (1) The patchlike cortical aggregates of intact radial nerve inputs from the hand underwent a two- to three-fold expansion. This expansion was not related to peripheral changes in the radial nerve skin territory, but was due to rapid central decompression of radial nerve dominance patches. (2) The largest changes involved patches in lateral to central locations of the hand map. (3) The expanded patches occupied cortical zones that were activated by inputs from the digits, palm, and posterior hand prior to injury. These receptive field shifts were initiated within minutes after injury. (4) Receptive fields of neurons within expanded radial nerve patches were normal in size. (5) Besides changes involving radial nerve inputs from the hand, there was a small expansion of forelimb inputs into the preinjury hand cortex; however, the representation of face inputs did not expand into this cortex. (6) Finally, neurons across 50–69% of the hand cortex were unresponsive to tactile stimuli acutely after this injury. These findings indicate that the distribution patterns of nerve dominance aggregates in adult primates begin changing within minutes after nerve injury. Cortical changes involving specific inputs occupy similar extents and locations of cortex, and are arranged in highly consistent patterns, in different individuals. It is suggested that this consistency reflects specific patterns of central sensitization or disinhibition that are triggered by the injury.
Pharmacology of novel GABA receptors found on rod horizontal cells of the white perch retina
Authors: Qian H , Dowling JE
Published: April 2018

A novel type of GABA receptor is present on rod-driven (H4) horizontal cells of the white perch retina (Qian and Dowling, 1993a). These receptors have been tentatively termed GA-BAC receptors. In this study, the pharmacological properties of these receptors were further investigated by applying several conformationally restricted GABAA receptor agonists, GABAA antagonists, and a GABAB agonist to the H4 horizontal cells. GABA analogs locked in a partially folded conformation had a variety of effects. Isonipecotic acid had no effect on these receptors, whereas isoguvacine activated them but with low potency (EC50 = 137 microM). THIP (4,5,6,7-tetrahydroisoxazolo[5,4- c]pyridin-3-ol) acted as a competitive antagonist on these receptors with an inhibition constant of 82.5 microM. P4S (piperidine-4-sulfonic acid) activated the receptors at high concentrations (> 1 mM), but at lower concentrations it was a competitive antagonist with an inhibition constant of 80.9 microM. 14AA (imidazole-4-acetic acid), a GABA analog with an extended conformation, potently inhibited the GABA responses on H4 horizontal cells with an inhibition constant of 1.67 microM. Muscimol, which can assume both partially folded and extended conformations, acted as a mixed agonist-antagonist. The GABA responses on H4 horizontal cells were resistant to several competitive GABAA receptor antagonists including bicuculline, hydrastine, and SR-95531, but they were very sensitive to picrotoxin (IC50 = 237 nM). The inhibition by picrotoxin was both competitive and noncompetitive in nature. On the other hand, TBPS (tert-butyl-bicyclophosphorothionate), another GABAA receptor channel blocker, had minimal effects on these receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Structure and function of retinal ganglion cells innervating the cat's geniculate wing: an in vitro study
Authors: Pu M , Berson DM , Pan T
Published: April 2018

We have examined in vitro the morphology and visual response properties of retinal ganglion cells innervating a component of the cat's lateral geniculate nucleus known as the geniculate wing (or retinorecipient zone of the pulvinar). Ganglion cells were first labeled in situ by retrograde transport of fluorescent microspheres from the geniculate wing. Labeled cells were injected intracellular with Lucifer yellow and biocytin in the isolated retina and visualized immunohistochemically. With one exception, stained cells appeared to belong to a single morphological class that corresponded closely to the epsilon cell of earlier descriptions (Leventhal et al., 1980; Rodieck and Watanabe, 1986). They had somas comparable in size to those of beta cells and large, sparse dendritic trees that ramified in the inner (ON) sublayer of the inner plexiform layer. Dendritic fields increased in size with eccentricity, but only within the central retina, and were among the largest so far reported for cat ganglion cells, exceeding those of alpha cells at most eccentricities. Dendritic profiles were typically elliptical with long axes pointing toward the area centralis. Axons were about as thick as those of beta cells and thicker than those of other varieties of non-alpha, non-beta ganglion cells. We recorded extracellularly from microsphere-labeled wing-projecting ganglion cells in a superfused, flattened eyecup preparation. All such cells exhibited sustained responses to standing contrast and had very large, concentric receptive fields with ON-centers and OFF-surrounds. Their response to gratings showed that they have relatively poor spatial resolution and a moderate amount of nonlinearity of spatial summation. These cells thus have many physiological response properties in common with ganglion cells previously termed “on-center tonic W-cells,” “on-center sluggish sustained cells,” and “Q-cells.” These findings indicate that ganglion cells innervating the cat's geniculate wing form a structurally and functionally homogeneous class. Their large dendritic and receptive fields and low-pass spatial frequency tuning suggest that fine spatial resolution is not required for the execution of their functional role(s).
Conserved spatial learning in cooled rats in spite of slowing of dentate field potentials
Authors: Moser EI , Andersen P
Published: April 2018

Behaviorally induced brain temperature changes have significant effects on field potentials recorded in the hippocampal formation. All components of the field potential are slowed during cooling. Field excitatory postsynaptic potentials (f-EPSPs) are often reduced, while the population spike is increased in this state. To investigate whether such synaptic alterations affect hippocampus-dependent learning, we have compared the effects of reduced brain temperature on dentate field potentials and spatial learning in a Morris water maze. Rats were implanted with thermistors in the brain. A subset of the rats received electrodes for field potential recording in the perforant path-granule cell synapses of the dentate gyrus. After recovery, the rats were cooled by swimming in a pool of water. This invariably led to a brain temperature reduction of several degrees centigrade and a delay of the extracellular response. In addition, the field potential changed as described above. The effect of these changes on spatial learning in a second pool, the water maze, was determined by first cooling and then reheating each rat to a given level of brain temperature prior to each spatial training session. In spite of marked changes in dentate field potentials, all rats trained at brain temperatures above 30 degrees C learned to find the submerged platform similarly well. The speed of acquisition and the final precision of search behavior were also similar in these rats. Only rats that had been cooled below 30 degrees C failed to locate the hidden target. These animals also showed clear evidence of motor impairment.(ABSTRACT TRUNCATED AT 250 WORDS)
Distribution of carbohydrate epitopes among disjoint subsets of leech sensory afferent neurons
Authors: Zipser K , Erhardt M , Song J , Cole RN , Zipser B
Published: April 2018

Carbohydrate recognition plays an important role in the development of normal projections of sensory afferent neurons in the leech CNS. Four different carbohydrate epitopes are expressed by sensory afferents on their 130 kDa surface proteins: all sensory afferents share a common carbohydrate epitope (CE0) that helps them to enter and project diffusely across the synaptic neuropil; a restricted expression of three other carbohydrate epitopes (CE1, CE2, and CE3) serves to distinguish three subsets of sensory afferents. We examined the subsets of sensory afferents defined by their subset carbohydrate epitopes in the leech lip, skin, gut, and CNS. We established that the CE1, CE2, and CE3 subset epitopes define disjoint subsets of neurons by double labeling sensory afferents with monoclonal antibodies for different pairs of subset epitopes. We found that CE2 and CE3 afferents populate the lip and skin, but not the gut, and that these two subsets of sensory afferents have convergent projection patterns in the CNS. We found that CE1 afferents populate the gut and skin, but not lips; furthermore, their CNS projections diverge from those of CE2 and CE3 afferents. Our data fit the hypothesis that these carbohydrate epitopes are related to sensory modality of afferent subsets.
The appearance of NPY and VIP in sympathetic neuroblasts and subsequent alterations in their expression
Authors: Tyrrell S , Landis SC
Published: April 2018

Mature sympathetic neurons contain one or more neuropeptides in addition to a classical neurotransmitter. We compared the development of two peptides, neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP), in rat superior cervical (SCG) and stellate ganglia. NPY immunoreactivity (-IR) was first detected at embryonic day (E) 12.5. It was of similar immunofluorescence intensity in almost all tyrosine hydroxylase (TH)-IR cells. In contrast, VIP-IR, of variable fluorescence intensity, appeared at E14.5 in a subset of TH-IR cells in the stellate ganglion but not in SCG. Both peptides were present in bromodeoxyuridine-labeled neuronal precursors as well as neurons. The intensity of NPY immunofluorescence increased until E16.5. Subsequently, while it continued to increase in some neurons, the intensity decreased in others so that at birth approximately 55% of SCG and stellate neurons were NPY-IR. Developmental changes in NPY concentration, determined by radioimmunoassay, were similar in both ganglia, increasing between E14.5 and E16.5 and then decreasing 60% between E16.5 and birth. VIP expression differed from that of NPY. The proportion of VIP-IR cells began to decrease the day after VIP-IR was first detected. Although VIP-IR was present in one-third of E14.5 TH-IR stellate cells, at birth only 2% were VIP-IR. VIP-IR, measured by radioimmunoassay, was uniformly severalfold more concentrated in the stellate than SCG, and its concentration decreased throughout embryonic development, 40% between E14.5 and E16.5 and 95% by birth. In situ hybridization revealed detectable mRNA for both NPY and VIP at E14.5 in stellate ganglion and mRNA for NPY, but not VIP, in SCG. Initially, ganglionic neuropeptide mRNA appeared uniformly distributed but became heterogeneous. Our data indicate that features of the diverse peptidergic phenotypes expressed by sympathetic neurons are present when peptides are first detected while others arise subsequently. The final acquisition of peptidergic phenotypic diversity is complex, entailing both early induction in many cells and subsequent restriction to specific subpopulations.
GABA synapses formed in vitro by local axon collaterals of nucleus accumbens neurons
Authors: Shi WX , Rayport S
Published: April 2018

GABAergic medium-spiny neuron axons not only form the principal projections of the nucleus accumbens (nAcc) but also branch locally in a dense network overlapping their own dendrites, suggesting that their recurrent synapses mediate the major information processing functions of the nAcc. We used postnatal nAcc cultures to study these synapses individually. In culture, as in the intact nAcc, medium-spiny neurons account for over 95% of the cells and are GABAergic. Strikingly, these neurons showed a spike afterhyperpolarization (AHP) that was largely blocked by the GABAA antagonist bicuculline. The bicuculline-sensitive AHP occurred without or with latency, and met criteria for monosynapticity; consistent with this, dye fills showed the presence of recurrent axons and a low incidence of dye coupling. Blockade of Ca2+ influx eliminated this autaptic PSP, while TTX almost completely eliminated it, indicating that it is due to exocytic GABA release principally at axodendritic contacts. While blocking GABAB receptors had no direct effect on the autaptic PSP, activating these receptors with baclofen produced presynaptic inhibition, as well as directly mediated hyperpolarization; together, these actions increased the signal-to-noise ratio in the cellular response to synaptic inputs. Bicuculline also increased the signal-to-noise ratio; in addition, it induced burst firing and depolarization inactivation. In contrast, the indirect GABA agonist flurazepam and the GABA uptake blocker nipecotic acid each enhanced autaptic PSPs. Since autapses formed in vitro appear to be functionally equivalent to synapses between neighboring medium- spiny neurons that receive similar inputs, these results bear on the function of intrinsic GABA synapses in the intact nAcc. Thus, intrinsic GABA synapses are likely to regulate the signal-to-noise ratio in nAcc information processing and may be important targets for the modulatory actions of endogenous neurotransmitters and drugs.
Modulation of glycine affinity for NMDA receptors by extracellular Ca2+ in trigeminal neurons
Authors: Gu Y , Huang LY
Published: April 2018

Glycine and the divalent cation Ca2+ play key roles in regulating the activity of excitatory amino acid NMDA receptor channels. There is accumulating evidence that the concentration of glycine at the synaptic cleft is below a saturated level. We examined the effect of external Ca2+ on NMDA responses in various concentrations of glycine in isolated trigeminal neurons. We found that external Ca2+ potentiated NMDA responses and this potentiation occurred only when glycine sites were unsaturated. Since single-channel conductance decreases in the high external Ca2+ solution, the observation cannot be explained by an increase in Ca2+ influx through the channels. Studying the dose- response curves for glycine in different Ca2+ solutions, we found that the apparent dissociation constant (EC50) for glycine decreases with increasing external Ca2+ concentrations. Kinetics studies of glycine binding to NMDA receptors indicated that external Ca2+ causes a decrease in the off rate of the glycine binding, while having no effect on the on rate. Our analyses suggest that the apparent glycine affinity increases by about 3.7 times in Ca-containing solution. Thus, external Ca2+ contributes to the unusually high glycine affinity for NMDA receptors and may have a role in regulating the NMDA receptor channel activities during intensive or sustained neuronal stimulation.
Plasticity in the adult human oligodendrocyte lineage
Authors: Gogate N , Verma L , Zhou JM , Milward E , Rusten R , O'Connor M , Kufta C , Kim J , Hudson L , Dubois-Dalcq M
Published: April 2018

Preoligodendrocytes have been described in cultures and tissue prints of adult human white matter (Armstrong et al., 1992). To characterize further these precursors of human oligodendrocytes, we have investigated whether they express genes playing a critical role in oligodendrocyte development. In the intact human brain, platelet- derived growth factor receptor alpha (PDGF alpha R) and myelin transcription factor 1 (MyTI) transcripts are expressed in 1–2% of cells of the oligodendrocyte lineage (OL), and clusters of such cells can be found in the periventricular region. Myelin basic protein transcripts containing exon 2 information (exon 2+ MBP), which are characteristic of the premyelinating stage, are detected in 15–20% of OL cells in vivo. When OL cells are separated from human white matter and allowed to regenerate in vitro, a much larger proportion of these cells express developmentally regulated genes, while exon 2- MBP and proteolipid protein (PLP) transcripts characteristic of mature OL cells appear transiently downregulated. Basic fibroblast growth factor (bFGF), even in the presence of PDGF, does not promote DNA synthesis in these cultured OL cells. Yet bFGF induces human oligodendrocytes to regenerate their processes rapidly in vitro and to express O4 antigens as well as exon 2+ MBP, MyTI, and PLP transcripts. While bFGF accelerates early regenerative processes, it also maintains high expression of exon 2+ MBP transcripts in OL cells for up to 2 weeks in vitro. In contrast, high levels of insulin in the absence of bFGF allow accumulation of exon 2- MBP and PLP transcripts in most OL cells at 2–3 weeks in vitro. We propose that the myelinated human brain harbors a small pool of precursors of oligodendrocytes and that growth factor- regulated phenotypic plasticity rather than mitogenic potential accounts for the regeneration of oligodendrocytes in the initial stages of demyelinating diseases such as multiple sclerosis.
The algorithmic complexity of neural spike trains increases during focal seizures
Authors: Rapp PE , Zimmerman ID , Vining EP , Cohen N , Albano AM , Jimenez-Montano MA
Published: April 2018

The interspike interval spike trains of spontaneously active cortical neurons can display nonrandom internal structure. The degree of nonrandom structure can be quantified and was found to decrease during focal epileptic seizures. Greater statistical discrimination between the two physiological conditions (normal vs seizure) was obtained with measurements of context-free grammar complexity than by measures of the distribution of the interspike intervals such as the mean interval, its standard deviation, skewness, or kurtosis. An examination of fixed epoch data sets showed that two factors contribute to the complexity: the firing rate and the internal structure of the spike train. However, calculations with randomly shuffled surrogates of the original data sets showed that the complexity is not completely determined by the firing rate. The sequence-sensitive structure of the spike train is a significant contributor. By combining complexity measurements with statistically related surrogate data sets, it is possible to classify neurons according to the dynamical structure of their spike trains. This classification could not have been made on the basis of conventional distribution-determined measures. Computations with more sophisticated kinds of surrogate data show that the structure observed using complexity measures cannot be attributed to linearly correlated noise or to linearly correlated noise transformed by a static monotonic nonlinearity. The patterns in spike trains appear to reflect genuine nonlinear structure. The limitations of these results are also discussed. The results presented in this article do not, of themselves, establish the presence of a fine-structure encoding of neural information.
Tenascin demarcates the boundary between the myelinated and nonmyelinated part of retinal ganglion cell axons in the developing and adult mouse
Authors: Bartsch U , Faissner A , Trotter J , Dorries U , Bartsch S , Mohajeri H , Schachner M
Published: April 2018

The molecular determinants controlling the topographically restricted distribution of neural cells in the mammalian CNS are largely unknown. In the mouse, myelin-forming oligodendrocytes are differentially distributed along retinal ganglion cell axons. These axons are myelin free intraretinally and in the most proximal (i.e., retinal) part of the optic nerve, but become myelinated in the distal (i.e., chiasmal) part of the optic nerve. Tenascin protein and mRNA are detectable in increased amounts at the retinal end of the developing optic nerve before the arrival of oligodendrocyte progenitor cells and are restricted to this region in the adult optic nerve. Tenascin is a nonadhesive substrate for oligodendrocytes and their progenitor cells in vitro when offered as a substrate in choice with polyornithine. These observations suggest that tenascin is critical for the establishment and maintenance of the restricted distribution of myelin- forming oligodendrocytes along retinal ganglion cell axons of the mouse.
Representation of multiple sound sources in the owl's auditory space map
Authors: Takahashi TT , Keller CH
Published: April 2018

The barn owl's inferior colliculus contains a retina-like map of space on which a sound generates a focus of activity whose position corresponds to the location of the sound source. When there is more than one source of sound, the sound waves sum and may generate spurious binaural cues that degrade the auditory image. We investigated the signal conditions under which neurons in the owl's auditory space map are able to resolve two simultaneously active sound sources. We recorded from space map neurons responding to sounds from a pair of speakers separated in azimuth by 45 degrees and mounted on a rotatable arm. Stimuli consisted of a sum of sinusoids or pseudorandom noise bursts emitted simultaneously and at equal overall levels. The characteristics of the sounds in each speaker were varied, and the neuron's response was plotted as a function of the speaker pair's position. When the speakers emitted different sets of summed sinusoids, the cells responded to each speaker separately; that is, the cells were able to resolve two separate targets. However, when the speakers emitted identical summed sinusoids generating binaural cues that were identical to those of a single phantom source between the two speakers, the neurons responded when the speakers were on either side of their receptive fields. By manipulating the amplitude at which each speaker emitted the various frequencies, we could control the position, number, and size of the phantom sources detected by the cell. The cells also resolved two separate sources when they emitted noise bursts that were statistically independent or temporally reversed versions of one another. Since the overall spectra of such waveforms are identical, we suggest that the space map relies on differences between noise bursts that exist over brief time spans.
Multiple types of ryanodine receptor/Ca2+ release channels are differentially expressed in rabbit brain
Authors: Furuichi T , Furutama D , Hakamata Y , Nakai J , Takeshima H , Mikoshiba K
Published: April 2018

The neuronal Ca2+ signal is induced by a rise in the intracellular free Ca2+ concentration ([Ca2+]i), and is thought to be important for higher brain function. Dynamic changes in [Ca2+]i are affected by the spatial distributions of various Ca(2+)-increasing molecules (channels and receptors). The ryanodine receptor (RyR) is an intracellular channel through which Ca2+ is released from intracellular stores. To define the contribution of neuronal Ca2+ signaling via the RyR channel, we examined RyR type-specific gene expression in rabbit brain by in situ hybridization histochemistry. The neuronal RyR was composed of three distinct types, two types dominant in skeletal (sRyR) and cardiac (cRyR) muscle, respectively, and a novel brain type (bRyR). sRyR was distinguished by its high level of expression in cerebellar Purkinje cells. cRyR was predominantly expressed throughout nearly the entire brain, and was characterized by its markedly high level of expression in the olfactory nerve layer, layer VI of the cerebral cortex, the dentate gyrus, cerebellar granule cells, the motor trigeminal nucleus, and the facial nucleus. bRyR expression was the least widely distributed throughout the brain, and was high in the hippocampal CA1 pyramidal layer, caudate, putamen, and dorsal thalamus. This investigation demonstrates that the heterogeneous distribution of neuronal RyRs may be implicated in distinct Ca(2+)-associated brain functions. Moreover, it should be noted that cRyR, a typical CICR channel, is distributed widely throughout the brain, suggesting that in a variety of cell types, the amplification of neuronal Ca2+ signals is functionally accompanied by a rise in [Ca2+]i, such as Ca2+ influx stimulated by neuronal activity. This widespread distribution of the neuronal RyR family indicates that Ca2+ signals via the intracellular stores should be considered in studies of neuronal Ca2+ dynamics.
Implantation of AtT-20 or genetically modified AtT-20/hENK cells in mouse spinal cord induced antinociception and opioid tolerance
Authors: Wu HH , Wilcox GL , McLoon SC
Published: April 2018

AtT-20 cells, which make and release beta-endorphin, or AtT-20/hENK cells, an AtT-20 cell line transfected with the human proenkephalin gene and secreting enkephalin as well as presumably beta-endorphin, were implanted in mouse spinal subarachnoid space. Cell implants did not affect the basal response to thermal nociceptive stimuli. Administration of isoproterenol, believed to stimulate secretion from these cells, produced antinociception in groups receiving AtT-20 or AtT- 20/hENK cell implants but not in control groups receiving no cells. The antinociceptive effect of isoproterenol was dose related and could be blocked by the opioid antagonist naloxone. Implantation of these cells offers a novel approach for the study of tolerance. Mice receiving AtT- 20 cell implants developed tolerance to beta-endorphin and the mu- opioid agonist DAMGO, whereas mice receiving genetically modified AtT- 20/hENK cell implants developed tolerance to the delta-opioid agonist DPDPE. Genetically modified AtT-20/hENK cell implants, but not AtT-20 cell implants, reduced the development of acute morphine tolerance in the host mice. This finding is consistent with the suggestion that enkephalin alters development of opioid tolerance. These results suggest that opioid-releasing cells implanted around mouse spinal cord can produce antinociception and may provide an alternative therapy for chronic intractable pain.
Habituation of neurosecretory responses to extracellular ATP in PC12 cells
Authors: Cheever L , Koshland DE
Published: April 2018

Neuronally differentiated PC12 cells have been used as a model for habituation. These cells secrete norepinephrine in response to extracellular ATP, as well as other stimulants, and the response is diminished with repetitive stimulation. This loss of neurosecretory responsiveness displays characteristics commonly associated with habituative learning. These include an increase in both the rate and the relative degree of response loss with either increasing stimulation frequency or decreasing stimulus intensity, and selective generalization of the decreased responsiveness to heterologous stimuli. In PC12 cells, the loss of neurosecretory responsiveness appears to be entirely caused by stimulation-dependent inactivation of the ATP-gated cation channel. Several unusual properties of this channel apparently allow its regulation to produce the behaviors associated with short- term habituation. Recovery of the ATP-gated channel requires several minutes, allowing habituation of responses to repetitive stimuli given at intervals of several minutes. Inactivation of the ATP-gated channel may be proportionately faster in response to lower ligand concentrations, allowing habituation to be more rapid in response to stimuli of weaker intensity.
Voltage-sensitive calcium channels in spinal nociceptive processing: blockade of N- and P-type channels inhibits formalin-induced nociception
Authors: Malmberg AB , Yaksh TL
Published: April 2018

The role of spinal voltage-sensitive calcium channels (VSCC) in a behavioral model of prolonged nociception was examined in rats. Blockade of VSCC by the trivalent cations neodymium (NdCl3) and lanthanum (LaCl3) resulted in a dose-dependent suppression of both phases of the response to formalin. omega-Conopeptides, which selectively block N-type VSCC, also produced a dose-dependent inhibition of both the initial behavior [phase 1; ED50 (nmol): SNX-111 (0.003) > SNX-185 (0.010) > SNX-239 (0.16) >> SNX-159 (> 0.26); SNX-199 (> 0.30)] and the facilitated response [phase 2; ED50 (nmol): SNX-111 (0.003) > SNX-185 (0.009) > SNX-239 (0.020) > SNX-159 (0.120) = SNX-199 (0.230)]. In contrast, SNX-231 (0.24 nmol), which is selective for a non-L/non-N site and also the L-type VSCC blockers nifedipine (24 nmol), nimodipine (29 nmol), verapamil (200 nmol), and diltiazem (220 nmol), had minimal effects on either phase of the formalin test at the highest dose examined. The P-type channel blocker omega-agatoxin IVA produced a 40% inhibition of phase 1 at the highest dose and phase 2 was suppressed in a dose-dependent fashion (ED50, 0.001 nmol). The response latency to a high-threshold thermal stimulus (the 52.5 degrees C hot plate) was moderately (20%) increased by NdCl3 (0.30 nmol) and SNX-111 (0.008 nmol), but not verapamil (200 nmol) and omega-agatoxin IVA (0.006 nmol). High doses of the N-type VSCC produced characteristic shaking behavior, serpentine-like tail movements, and impaired coordination. However, at antinociceptive doses there was no significant motor effect, though three of the N-type antagonists produced some tail movements. These studies demonstrate that VSCC of the N- and P-type, but not L-type, are involved in facilitated nociceptive processing at the spinal level.
Na(+)-dependent, fluoxetine-sensitive serotonin uptake by astrocytes tissue-printed from rat cerebral cortex
Authors: Dave V , Kimelberg HK
Published: April 2018

Previous studies have established that rat primary astrocyte cultures prepared from several brain regions of 1–4-d-old rats exhibit high- affinity, Na(+)-dependent and fluoxetine-sensitive serotonin (5-HT) uptake with a Km for 5-HT of 0.4 microM and a Ki for fluoxetine of 23 nM, which correspond to the characteristics for this transport for other brain preparations. However, it is not known whether astrocytes in situ show such uptake. We addressed this question by performing 3H-5- HT uptake experiments on cortical astrocytes, within 4 hr of isolating them from 6- and 21-d-old rats by the tissue-print technique. Quantitative autoradiography was combined with GFAP and neurofilament (NF) immunocytochemistry to distinguish astrocytic from neuronal 3H-5- HT uptake. In composition, the tissue-printed (TP) cells and processes were 60–70% GFAP (+) and 10–15% NF(+). 3H-5-HT uptake (0.3 microM 5-HT, 3.4 microCi/ml) in both tissue-printed GFAP(+) astrocytes and NF(+) structures was sensitive to 1 microM fluoxetine and was also Na+ dependent. More than 90% of TP astrocytes from 6- and 21-d-old rats and 100% of NF(+) structures from 21-d-old rats showed positive 3H-5-HT uptake (defined as > or = 31 grains/10(3) microns2). The highest level of uptake (> or = 191 grains/10(3) microns2) was never observed in TP astrocytes but was exhibited by about half of the NF(+) structures. In other experiments were found that 3H-5-HT uptake by 6-d-old TP astrocytes was comparable to uptake by postnatal age-matched primary cultured astrocytes that were grown in fetal bovine serum (FBS). However, primary cultured astrocytes grown in horse serum showed lower uptake than that observed with FBS, a finding similar to previous results in cultures where 3H-5-HT uptake was measured per milligram of cell protein. These results imply that high-affinity, Na(+)-dependent and fluoxetine-sensitive 5-HT uptake occurs in rat cortical astrocytes in situ.
Pathway-specific variants of AMPA receptors and their contribution to neuronal signaling
Authors: Raman IM , Zhang S , Trussell LO
Published: April 2018

Neurons of the nucleus magnocellularis (nMAG) of the chick express AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate) receptors displaying unusually rapid kinetics of desensitization (Raman and Trussell, 1992a). To investigate whether fast AMPA receptors are present in other auditory neurons, we compared the properties of AMPA receptors in auditory as well as nonauditory cells. These included neurons of nMAG, the nucleus angularis, the nucleus laminaris, the cochlear ganglion, the Purkinje cell layer of the cerebellum, the ventral horn of the spinal cord, and the brainstem nucleus of the glossopharyngeal nerve (ncIX). Rapid application of glutamate to voltage-clamped outside-out membrane patches indicated that AMPA receptors in the four types of auditory cells had significantly faster kinetics of desensitization than did the three types of nonauditory neurons. Channel kinetics in auditory (nMAG) and nonauditory (ncIX) cells were also compared by means of spectral analysis and the time course of current deactivation upon removal of glutamate. Both techniques revealed a burst duration for nMAG channels of 400–500 musec at room temperature, two to three times shorter than for ncIX cells. Single channels in nMAG had a burst duration of 550 musec and an open time of approximately 150 musec. Miniature excitatory postsynaptic currents of brainstem auditory neurons in slices were also brief, with decay constants of 150–250 musec at 29–32 degrees C. We demonstrated that the fast kinetics of this AMPA receptor are physiologically important, since cyclothiazide, which reduces desensitization and prolongs synaptic currents, doubled the relative refractory period of orthodromic spikes in nMAG cells in brain slices. We conclude that auditory brainstem neurons express a specialized subtype of AMPA receptors. This “fast” AMPA receptor may be useful in transmitting signals necessary for sound localization.
Activity of descending propriospinal axons in the turtle hindlimb enlargement during two forms of fictive scratching: broad tuning to regions of the body surface
Authors: Berkowitz A , Stein PS
Published: April 2018

We recorded the activity of descending propriospinal axons at the caudal end of a seven-segment (D3-D9) turtle spinal cord preparation. These seven spinal segments contain sufficient neural circuitry to select and generate fictive rostral scratching or fictive pocket scratching in response to tactile stimulation in the appropriate region of the body surface. Each turtle received two spinal transections, one just caudal to the forelimb enlargement and one in the middle of the hindlimb enlargement. Descending propriospinal axons were recorded extracellularly from the hindlimb enlargement on one side of the body, while the ipsilateral or contralateral body surface was stimulated. Concurrent recordings were made from ipsilateral and contralateral hindlimb muscle nerves to monitor fictive scratch motor patterns. We found that most tactilely responsive descending propriospinal axons were excited by stimulation anywhere within the rostral scratch or pocket scratch receptive fields on at least one side of the body, and often on both sides. The activity of these neurons was usually rhythmically modulated during fictive rostral scratching and fictive pocket scratching. Many neurons with large excitatory receptive fields generated action potentials at their highest rate during stimulation of a particular region of the body surface on one side, and generated action potentials at progressively lower rates during stimulation of sites progressively farther away. Thus, these units were broadly tuned to a region of the body surface. Some were tuned to a region of the rostral scratch receptive field and others were tuned to a region of the pocket scratch receptive field. These data suggest that selection of the appropriate form of scratching, rostral or pocket, may be mediated by populations of broadly tuned neurons rather than by highly specialized neurons.
Glycinergic synapses in the rod pathway of the rat retina: cone bipolar cells express the alpha 1 subunit of the glycine receptor
Authors: Sassoe-Pognetto M , Wassle H , Grunert U
Published: April 2018

Glycine receptors (GlyRs) and their role in retinal circuitry were analyzed immunocytochemically in the rat retina. Specific antibodies against the alpha 1 subunit of the GlyR and against the GlyR-associated protein gephyrin, respectively, were used. In the inner plexiform layer (IPL), both antibodies produced a punctate label that was shown by electron microscopy to occur at synapses. Gephyrin-like immunoreactivity (-LI) was more widely distributed, indicating that gephyrin might also occur at nonglycinergic synapses. At the ultrastructural level, gephyrin-LI was found at the cytoplasmic face of postsynaptic membranes of amacrine and ganglion cells, but was never detected in bipolar cell axons. Immunoreactivity for the alpha 1 subunit was concentrated in the cleft of conventional synapses made by amacrine cell processes onto ganglion cell dendrites and cone bipolar axons. The latter synapses differ from other glycinergic synapses since they are not labeled by the antibody against gephyrin used in this study. In order to identify the type of bipolar cell involved in these synapses, the distribution of the alpha 1 subunit was compared with that of recoverin-immunoreactive cone bipolar cells and with that of parvalbumin-immunoreactive All-amacrine cells. Double-label immunofluorescence showed that, in the outer part of the IPL, 75% of the alpha 1-immunoreactive puncta were colocalized with recoverin- positive bipolar cell axons and 71% of the alpha 1-immunoreactive puncta were colocalized with parvalbumin-positive All-amacrine processes. Hence, the alpha 1 subunit of the GlyR is present at the chemical synapses established by All-amacrine cells with OFF-cone bipolar cells and OFF-ganglion cells. These synapses play a key role in the transmission of scotopic signals through the OFF-channel of the rod pathway.
Spatial and temporal expression patterns of two sodium channel genes in Drosophila
Authors: Hong CS , Ganetzky B
Published: April 2018

Genetic and molecular studies have identified two different sodium channel genes in Drosophila, para and DSC1. The functional contributions of the para-encoded channel have been inferred from analysis of mutant phenotypes. However, no mutations of DSC1 have been identified, so the in vivo functions of the channel it encodes are not yet known. To learn more about the possible functions of DSC1 in the Drosophila nervous system compared with those of para, we have characterized the expression patterns of these two sodium channel genes at embryonic, larval, pupal, and adult stages by tissue in situ hybridization, para encodes the predominant type of sodium channel and is ubiquitously transcribed throughout the CNS and PNS at all developmental stages. The expression pattern of DSC1 is very different from para during embryonic and larval stages during which there are very few DSC1-expressing cells in either the CNS or PNS. Double- labeling studies suggest that some of these cells are non-neuronal. However, in pupal and adult stages, para and DSC1 have completely overlapping patterns of expression in the CNS and retina. In the pupal and adult, PNS expression of these genes is still distinct because only para transcripts are detected in wing sensory neurons. The strong and widespread expression of DSC1 in the CNS of pupae and adults suggests that the DSC1 channels are likely to provide an important function in neurons during these stages. Since most, if not all, neurons in the pupal and adult CNS express both para and DSC1, these two sodium channel genes probably subserve distinct functions within these cells. Our results provide the background for elucidating the respective in vivo contributions of para and DSC1 to neuronal excitability and for dissecting the regulatory mechanisms that underlie their different patterns of expression.