bluuebunny/crossref_metadata_2025 huggingface dataset:
The lateral nucleus of the amygdala mediates expression of the amphetamine-produced conditioned place preference
Authors: Hiroi N , White NM
Published: March 2018

We investigated the involvement of the hippocampal formation and the amygdala in the acquisition and expression of the amphetamine-produced conditioned place preference (CPP). Animals were conditioned in four sessions that included two pairings of d-amphetamine (2.0 mg/kg, s.c.) with one of two distinct compartments and two pairings of vehicle with the other compartment in a counterbalanced manner. Animals' preferences for the compartments were then tested in the absence of amphetamine. The CPP was attenuated by preconditioning electrolytic or excitotoxic lesions of the lateral nucleus of amygdala, but not by electrolytic lesions of the central or basolateral nucleus of amygdala, endopiriform nucleus, or ventral hippocampus or by radio-frequency lesions of the fornix-fimbria. When the lateral nucleus of amygdala was damaged by electrolytic or excitotoxic lesions after conditioning, animals failed to express an amphetamine-produced CPP. These results demonstrate that expression of the amphetamine-produced CPP is mediated by intrinsic neurons of the lateral nucleus of the amygdala, and that neither acquisition nor expression of the CPP is mediated by the central or basolateral amygdaloid nucleus or the hippocampus-accumbens projection. Combined with our previous finding that the expression of the amphetamine-produced CPP is also mediated by dopamine receptor activation in the nucleus accumbens (Hiroi and White, 1989, 1990), it could be suggested that the lateral nucleus of the amygdala and dopamine terminals in the nucleus accumbens are parts of the neural circuitry that mediates the expression of the amphetamine-produced CPP.
Postsynaptic modulation of rectifying electrical synaptic inputs to the LG escape command neuron in crayfish
Authors: Edwards DH , Heitler WJ , Leise EM , Fricke RA
Published: March 2018

The lateral giant (LG) tail-flip escape system of crayfish is organized to provide a massive convergence of mechanosensory inputs onto the LG command neuron through electrical synapses from both mechanosensory afferents and interneurons. We used electrophysiological techniques to show that the connections between three major mechanosensory interneurons and LG rectify, and that their inputs to LG can be reduced by postsynaptic depolarization and increased by postsynaptic hyperpolarization. The mechanosensory afferents and interneurons are excited by sensory nerve shock, and the components of the resulting LG PSP can be similarly modulated by the same postsynaptic potential changes. Because these inputs are all made through electrical synapses, we conclude that they are rectifying connections, as well. To test the physical plausibility of this conclusion, we developed an electrical model of the rectifying connection between a mechanosensory interneuron and LG, and found that it can reproduce all the qualitative features of the orthodromic and antidromic experimental responses. The ability of postsynaptic membrane potential to modulate inputs through rectifying electrical synapses is used in the escape system to enhance LG's relative sensitivity to novel, phasic stimuli. Postsynaptic depolarization of LG produced by earlier inputs “reverse-biases” the rectifying input synapses and reduces their strength relative to times when LG is at rest.
Cocaine and amphetamine interact at 5-HT synapses through distinct mechanisms in guinea-pig prepositus hypoglossi
Authors: Bobker DH , Williams JT
Published: March 2018

Intracellular recordings were made from guinea-pig prepositus hypoglossi (PH) neurons in vitro. Neurons within this nucleus are innervated by terminals that release 5-HT (serotonin) to mediate an IPSP. Cocaine caused a concentration-dependent prolongation of that IPSP, while having no effect on either membrane potential or firing rate. Cocaine also caused an increase in the IPSP amplitude at lower concentrations (less than or equal to 1 microM) and a decrease at higher concentrations. The selective 5-HT uptake inhibitor fluoxetine also prolonged the IPSP duration but depressed the amplitude at all concentrations tested. The effects of cocaine on IPSP duration can be completely accounted for by inhibition of 5-HT uptake. The depression of the IPSP is most likely due to a presynaptic effect, because cocaine augmented the response to applied 5-HT. Amphetamine (3–300 microM), unlike cocaine, changed the membrane potential. At lower concentrations, it caused a ketanserin-sensitive depolarization, while higher concentrations resulted in a spiperone-sensitive hyperpolarization. The hyperpolarization was most likely caused by the evoked release of 5-HT, while the depolarization may have been due to a direct effect of amphetamine on 5-HT2 receptors. Amphetamine also acted as a weak uptake inhibitor. The effects of cocaine, but not those of amphetamine, were observed at concentrations that are attained during self-administration.
Catechol oxidation by peroxidase-positive astrocytes in primary culture: an electron spin resonance study
Authors: Schipper HM , Kotake Y , Janzen EG
Published: March 2018

In rodents, chronic estrogenization has been shown to induce degeneration of dendrites and myelin figures in the hypothalamic arcuate nucleus adjacent to peroxidase-positive astrocyte processes. Because in this brain region estradiol is metabolized to 2- hydroxyestradiol (catecholestrogen), we hypothesized that the latter may be oxidized by the astrocytic peroxidase activity to cytotoxic ortho-semiquinones as occurs in peripheral tissues. Cysteamine induces nonenzymatic peroxidase activity in cultured astroglia identical to that observed in vivo. Using electron spin resonance, we demonstrate robust peroxidase-catalyzed oxidation of 2-hydroxyestradiol and dopamine by cysteamine-pretreated astrocyte cultures relative to untreated controls. These results implicate the peroxidase-positive astrocytes in the pathogenesis of estradiol-related hypothalamic damage, parkinsonism, and other free-radical-related neurologic disorders.
Spreading depression increases immunohistochemical staining of glial fibrillary acidic protein
Authors: Kraig RP , Dong LM , Thisted R , Jaeger CB
Published: March 2018

Reactive astrocytosis is a process by which astrocytes respond to brain injury by showing an increase in glial fibrillary acidic protein (GFAP) staining that is associated with hypertrophy and/or hyperplasia of these cells. Because spreading depression (SD) is a perturbation uncomplicated by neuronal necrosis and is seen in both in vivo and in vitro neural structures, we sought to determine whether SD was a sufficient stimulus to induce enhanced GFAP staining. SD was elicited in anesthetized rats by application of KCI to parietal cortex for 3 hr; equimolar NaCI was applied to contralateral cortex. SD was confirmed by monitoring DC potentials in frontal neocortices. Animals were allowed to recover for 48 hr, and their brains were processed for semiquantitative and computer-based analyses of GFAP staining intensity. Experimental GFAP staining was referenced to contralateral control levels. Neocortical SD (13–37 SDs) was associated with a significant (p less than 10(-4)), 43% increase in GFAP staining intensity, which remained statistically greater than normal for more than 2 weeks. If SD was inhibited by combined hyperoxia and hypercarbia, only a nonsignificant (p greater than 0.20), 7% increase in GFAP staining was seen. Thus, SD may be a useful physiologic process with which to begin to explore the cellular mechanisms that induce the transformation of normal astrocytes into reactive species.
The action of halothane on stimulus-secretion coupling in clonal (GH3) pituitary cells
Authors: Stern RC , Herrington J , Lingle CJ , Evers AS
Published: March 2018

The effect of halothane on the physiological response to excitatory stimuli was assessed in clonal (GH3) pituitary cells. Halothane, at concentrations used to produce general anesthesia in animals (0.25–0.76 mM), inhibited thyrotropin-releasing hormone (TRH)-induced prolactin (PRL) secretion. The sustained (extracellular calcium-dependent) phase of PRL secretion was 70 +/- 7% inhibited by the highest concentration of halothane tested (0.76 mM); 50% inhibition was produced by approximately 0.4 mM halothane. The early (largely inositol trisphosphate-mediated) phase of secretion was less sensitive to halothane; 0.76 mM halothane produced 18 +/- 2% inhibition of the early phase of secretion. Consistent with these observations, halothane inhibited (IC50 approximately 0.45 mM) the sustained phase of the TRH- induced rise in intracellular calcium ([Ca2+]i) to a greater extent than the initial [Ca2+]i peak. The sustained phase of the [Ca2+]i elevation was inhibited by 75 +/- 7% at the highest concentration of halothane tested (0.76 mM), whereas the peak [Ca2+]i was only inhibited by 14 +/- 5%, consistent with the observation that halothane did not inhibit TRH-stimulated inositide hydrolysis in these cells. Halothane (0.5 mM) did not inhibit phorbol ester- or ionomycin-induced PRL secretion, indicating that halothane has inconsequential effects on the secretory apparatus. Halothane (0.5 mM) also inhibited KCl-induced PRL secretion by 50–80% and the corresponding KCl-induced rise in [Ca2+]i by 68 +/- 6%. These data indicate that halothane inhibits secretagogue- stimulated PRL secretion by reducing the elevation of [Ca2+]i produced by calcium (Ca2+) influx.
Hippocampal theta field activity and theta-on/theta-off cell discharges are controlled by an ascending hypothalamo-septal pathway
Authors: Smythe JW , Cristie BR , Colom LV , Lawson VH , Bland BH
Published: March 2018

The nature of the control of hippocampal formation field activity [theta (theta) and large-amplitude irregular activity (LIA)] and theta- on/theta-off cell discharges by an ascending hypothalamo-septal pathway was investigated in urethane-anesthetized rats. Electrical stimulation of the dorsomedial-posterior hypothalamus in the range of 0.1–1.0 mA in 0.1-mA steps produced theta in the hippocampal formation, with a linear positive relation between stimulus intensity, theta frequency, and theta amplitude. Reversible blockade of the medial septal (MS)/vertical limb of the diagonal band of Broca (vDBB) region by microinjection of procaine hydrochloride abolished spontaneous and hypothalamically elicited theta, resulting in a field activity at 1-min post-procaine that had a lower power than pre-procaine LIA levels. The efficacy and recovery of the MS/vDBB suppression was tested at 1, 10, 20, 30, 40, 50, and 60 min post-procaine using 0.5, 0.8, and 1.0 mA of hypothalamic stimulation. All three of the dependent measures of hippocampal field activity (frequency, amplitude, and power) showed a progressive recovery during the 60-min post-procaine period. Frequency exhibited a rapid recovery with a shallow slope between 20 and 60 min post- procaine. In contrast, the amplitude and power of theta exhibited a gradual recovery with a steeper slope between 20 and 60 min post- procaine. During the time of maximal MS/vDBB suppression, theta-on cell discharges were reduced to 0 in most cases. The initial recovery of theta-on cells in the post-procaine condition was correlated with the first appearance of theta and was characterized by low discharge rates.
Chronic androgen treatment increases action potential duration in the electric organ of Sternopygus
Authors: Mills A , Zakon HH
Published: March 2018

The quasi-sinusoidal electric organ discharge (EOD) of the weakly electric fish Sternopygus is involved in communication and orientation. Each monophasic pulse of the low-intensity EOD is a compound action potential (AP) from the simultaneously firing electrocytes of the electric organ. EOD frequency is lower and EOD pulse duration longer in sexually mature males than in sexually mature females; exogenous androgen lowers EOD frequency and increases EOD pulse duration. In order to determine the contribution of single electrocyte spikes to the entire EOD pulse, APs were induced by intracellular current injection in single electrocytes of isolated pieces of electric organ. Each AP looks very similar to the externally recorded EOD pulses, and AP duration (APD) is significantly correlated with EOD pulse duration (r = 0.48; p less than 0.0005). The APD is slightly longer when compared to the EOD pulse duration, but this difference is likely due to the stimulation paradigm. Fish treated with dihydrotestosterone showed a decrease in EOD frequency, increase in EOD pulse duration, and corresponding increase in APD; control fish showed random, insignificant changes in EOD wave form and APD. Evidence presented here shows that changes in the passive membrane properties are unlikely to be responsible for the APD increase. The possibility is discussed that androgens act directly upon the electric organ, ultimately altering the ionic currents that produce the AP.
Responses of rod bipolar cells isolated from the rat retina to the glutamate agonist 2-amino-4-phosphonobutyric acid (APB)
Authors: Yamashita M , Wassle H
Published: March 2018

Isolated rod bipolar cells were obtained by enzymatic (papain) and mechanical dissociation of the adult rat retina. Virtually all intact bipolar cells in the dissociates expressed protein kinase C (PKC) immunoreactivity, a selective marker for rod bipolar cells in the in vivo retina. Whole-cell recordings were performed using nystatin in the patch pipette to minimize washout of those cytoplasmic components necessary for the maintenance of ionic currents. At holding potentials of -33 mV, a tonic inward current was observed. The glutamate agonist 2- amino-4-phosphonobutyrate (APB) reduced this current by closing ion channels. Under normal conditions, Na+ appeared to be the main charge carrier. Both the internal and the external Ca2+ concentrations were found to exert a powerful influence on the APB-sensitive current. We conclude that the rod bipolar cell in situ is depolarized at light onset.
Tau gene expression in rat sensory neurons during development and regeneration
Authors: Oblinger MM , Argasinski A , Wong J , Kosik KS
Published: March 2018

In the mature rat dorsal root ganglion (DRG), only one tau isoform is expressed, and this protein (110 kDa in apparent molecular weight) is considerably larger in size than the predominant tau isoforms found in brain. The size of the mRNA encoding the “big” tau mRNA in DRG [approximately 8 kilobases (kb)] is also much larger than that of the major rat brain tau mRNA species (approximately 6 kb). In this study, we examined the pattern of normal developmental changes in expression of this high-molecular-weight (HMW) tau and its encoding mRNA and also determined how axonal injury of adult DRG neurons effected the expression of this gene. RNA blotting experiments revealed that higher levels of HMW tau mRNA were present in the DRG at early postnatal times than in the adult. Immunoblotting of total DRG protein using a monoclonal tau antibody revealed that the immature DRG (7 d postnatal) contained a 62-kDa tau isoform in addition to the HMW tau isoform that was expressed in the adult DRG. Neither of the tau isoforms expressed in the immature DRG was present to any significant extent in either immature or adult rat brain. To examine how tau expression changed in adult DRG neurons during regeneration, the sciatic nerves of rats were unilaterally crushed, and the L4 and L5 DRG were harvested 1, 7, and 14 d later.
Evidence for the ventral origin of oligodendrocyte precursors in the rat spinal cord
Authors: Warf BC , Fok-Seang J , Miller RH
Published: March 2018

The neuroepithelial cells of the mammalian neural tube are thought to give rise to all classes of differentiated neurons and macroglial cells in the adult CNS. In most cases, the regulation and timing of commitment of neuroepithelial cells to specific differentiative pathways are unknown. It has been proposed that in developing spinal cord, the macroglial cells--astrocytes and oligodendrocytes--arise either by the direct transformation of radial glial cells in the developing cord or, alternatively, by the differentiation of distinct precursor cells which migrate to presumptive white matter from the region of the central canal during development. In this study, the timing of oligodendrocyte differentiation in different levels of the spinal cord and the capacity of specific regions of the spinal cord to give rise to oligodendrocytes at various ages was tested in vitro. At embryonic day 14, all complete segments, as well as all ventral regions along the rostral-caudal axis of the spinal cord, have the capacity for oligodendrogenesis. By contrast, dorsal regions of the thoracic and lumbar spinal cord do not develop the capacity for oligodendrogenesis until later in development. The capacity of dorsal rat spinal cord to give rise to oligodendrocytes appears to be associated with the ventral- to-dorsal migration of oligodendrocyte precursors. These observations suggest that commitment to an oligodendrocyte differentiative pathway appears to occur in a distinct population of ventrally located glial precursors in the embryonic rat spinal cord.
Serotonin mimics tail shock in producing transient inhibition in the siphon withdrawal reflex of Aplysia
Authors: Fitzgerald K , Carew TJ
Published: March 2018

Tail shock-induced modulation of the siphon withdrawal reflex of Aplysia has recently been shown to have a transient inhibitory component, as well as a facilitatory component. This transient behavioral inhibition is also seen in a reduced preparation in which a cellular reflection of the inhibitory process, tail shock-induced inhibition of complex EPSPs in siphon motor neurons, is observed. The biogenic amine serotonin (5-HT) is known to play a role in the facilitatory aspects of sensitization in Aplysia. The aim of this article was to examine whether 5-HT might also contribute to the inhibitory effects of tail shock in the siphon withdrawal reflex. To examine this question, we carried out two kinds of experiments. First, in the isolated abdominal ganglion, we recorded intracellularly from siphon motor neurons and examined the effects of 5-HT on (1) complex (polysynaptic) EPSPs, produced by siphon nerve stimulation, and, simultaneously, (2) monosynaptic EPSPs from siphon sensory neurons. We found that, paralleling the effects of tail shock in the reduced preparation, 5-HT produced transient inhibition of the complex EPSP; the monosynaptic EPSP was facilitated by 5-HT. Second, we examined the behavioral effects of 5-HT on siphon withdrawal in a reduced preparation. We found that 5-HT again paralleled tail shock by producing transient inhibition of the siphon withdrawal reflex. Our results suggest that, in addition to its well-established facilitatory role in reflex modulation in Aplysia, 5-HT might play an important inhibitory role, as well.
Existence of different subtypes of nicotinic acetylcholine receptors in the rat habenulo-interpeduncular system
Authors: Mulle C , Vidal C , Benoit P , Changeux JP
Published: March 2018

Neuronal nicotinic ACh receptors (nAChRs) are present in the rat medial habenula (MHB) and interpeduncular nucleus (IPN), two brain regions connected through the fasciculus retroflexus (FR). The goal of the present study was to compare the electrophysiological and pharmacological characteristics of nAChRs located at pre- and postsynaptic sites within the MHB-IPN system. nAChRs located on the soma of IPN neurons were studied using patch-clamp techniques and a preparation of acutely isolated neurons. Whole-cell currents evoked by Ach and nicotine showed an intense rectification at positive membrane potentials. nAChR channels were relatively nonselective for cations, had a unitary conductance of 35 pS, and were activated by several nicotinic agonists with the following rank order: cytisine greater than ACh greater than nicotine greater than dimethylphenylpiperazinium (DMPP). They were blocked by mecamylamine, hexamethonium, curare, and dihydro-beta-erythroidine (DHBE), but were insensitive to alpha- bungarotoxin and neuronal bungarotoxin. In contrast, nAChRs recorded on the soma of MHB neurons under equivalent experimental conditions exhibited different characteristics for single-channel conductance and agonist and antagonist sensitivity. The pharmacological properties of presynaptic nAChRs in the IPN were analyzed in a rat brain slice preparation. Stimulation of the FR produced a presynaptic afferent volley recorded in the rostral subnucleus of the IPN. Nicotinic agonists decreased the amplitude of the afferent volley with different efficacies: nicotine greater than cytisine greater than ACh greater than DMPP. The action of nicotine was insensitive to alpha-bungarotoxin and to neuronal bungarotoxin, but was blocked by mecamylamine, hexamethonium, curare, and DHBE, with IC50 values different from those reported for IPN postsynaptic nAChRs. This study thus demonstrates the functional diversity of nAChRs in the rat CNS.
An experimental analysis of in vivo guidance cues used by axons of spinal interneurons in the chick embryo: evidence for chemotropism and related guidance mechanisms
Authors: Yaginuma H , Oppenheim RW
Published: March 2018

To clarify axonal guidance mechanisms involved in pathway formation by spinal interneurons, the pattern of axonal outgrowth was examined following three kinds of perturbations: (1) rotation of three segments of the neural tube around the dorsal-ventral axis by 90 degrees or 180 degrees (D-V rotation), (2) rotation of three segments of the neural tube around the rostral-caudal axis (R-C rotation), and (3) transplantation of brainstem into thoracic spinal segments (BS transplantation). Following D-V rotation, it was observed that circumferential axons near the junction between rotated graft (RG) and host cord changed their course so as to project toward the ectopic floor plate. This supports the notion that the floor plate exerts a chemotropic-like effect on the directional projection of circumferential axons. The longitudinal fibers in the ventral funiculus (VF) were able to grow through the transplant junction when the VF was well apposed to the VF of the RG. However, in most cases, the longitudinal fibers in the VF that were not apposed to the VF of the RG made a medial turn at the junction. After turning, some of them made a U-turn into the contralateral VF, whereas others grew circumferentially around the junction zone, then exited the spinal cord; still others directly entered the RG. The majority of fibers that entered the RG were located in the VF, though a small number of such fibers were also located in both the lateral and dorsal funiculus (LF and DF, respectively). The fibers that entered the LF shifted ventrally, whereas the fibers in the DF remained within the DF. These results suggest that there may be some matching mechanism between specific fibers and the funiculus through which the fibers normally project. Moreover, there may be a barrier between the LF and the DF that prevents the fibers in the DF from shifting ventrally. In R-C rotation experiments, the projection of axons of dorsolateral border cells (DLB- cells), which are known to give rise almost exclusively to commissural ascending axons, was examined. Following the injection of HRP into the rostral junctional region, retrogradely labeled DLB-cells were observed in the rotated segments only on the side contralateral to the injection. Labeled DLB-cells were also observed in the segments caudal to the rotated segments. These results suggest that putative rostrocaudal directional cues that guide the axons of DLB-cells may arise from outside of the segments in which the decision to turn is made.
The origin of thalamic inputs to the "hand" representation in the primary motor cortex
Authors: Holsapple JW , Preston JB , Strick PL
Published: March 2018

We used retrograde transport of WGA-HRP to examine the origin of thalamic inputs to the “hand” representation in the primary motor cortex of macaques (Macaca nemestrina). Injections were placed in either the crest of the precentral gyrus or the rostral bank of the central sulcus. The sites for injection in the sulcus were determined by using intracortical stimulation to map the location of hand representation. We found that the precentral gyrus and central sulcus receive their predominant input from different subdivisions of the ventrolateral thalamus. Ventralis posterior lateralis pars oralis (VPLo) provides the most substantial input to a portion of the hand representation on the gyrus. In contrast, Ventralis lateralis pars oralis (VLo) provides the most substantial input to a portion of the hand representation in the sulcus. Prior studies have shown that VPLo is a major site of termination of cerebellar efferents and that VLo is a major site of termination of pallidal efferents. Thus, our results indicate that both the basal ganglia and the cerebellum “directly” influence the “hand” representation of the primary motor cortex.
Does low intracellular pH stop the motion of the Bulla circadian pacemaker?
Authors: Khalsa SB , Ralph MR , Block GD
Published: March 2018

The eye of the mollusk Bulla has proven itself useful as an in vitro neural circadian pacemaker. Here, we report that treatments applied to lower intracellular pH may stop the motion of this circadian pacemaker in a phase-dependent manner. Lowering the extracellular pH of the artificial seawater bath to 6.9, or application of the stilbene derivatives 4-acetamido-4′-isothiocyanostilbene-2,2′-disulfonic acid (SITS) or 4,4-di-isothiocyanostilbene-2,2′-disulfonic acid (DIDS), abolishes the circadian rhythm in optic nerve compound action-potential frequency. Because these treatments are known to lower intracellular pH, these data suggest that the pacemaker may be inhibited by low intracellular pH. In order to assess the state of the pacemaker during low extracellular pH treatment, pulses of seawater at pH 6.8 were applied, and the phase of the rhythm subsequent to the pulse was observed. All pulses started 1 hr after subjective dusk [circadian time (CT) 13] and were applied to eyes in constant darkness; pulse lengths varied from 4 to 47 hr for different preparations. The phases of the eye rhythms following pulses that ended before subjective dawn (about CT 24) were not different from untreated preparations. However, for pulses longer than 11 hr and therefore ending after subjective dawn, the subsequent phase of the rhythm was a function of the ending time of the pulse. These data suggest that the pacemaker's motion was stopped at dawn during the low-pH treatment and resumed following restoration of normal pH. To distinguish between phase and duration dependence of this effect in the above experiment, phase shifts were obtained to 14- hr pulses of pH 6.8 seawater applied at three different phases.
Extracellular dopamine and neurotensin in rat prefrontal cortex in vivo: effects of median forebrain bundle stimulation frequency, stimulation pattern, and dopamine autoreceptors
Authors: Bean AJ , Roth RH
Published: March 2018

In vivo microdialysis coupled with HPLC and radioimmuno-assay techniques were used to analyze dopamine (DA) and neurotensin (NT) in prefrontal cortical extracellular fluid following electrical stimulation of mesocortical axons. The release (overflow into the extracellular fluid) of both DA and NT increased with increasing number of impulses and with frequency. At the lowest frequency tested (2.5 Hz), DA release was significantly increased, while there was no significant increase in the release of NT. As the frequency of stimulation was increased from 2.5 to 20 Hz, the ratio of extracellular DA:NT decreased exponentially. Stimulation in a burst pattern produced greater release of both DA and NT than tonic stimulation when the number of impulses per second and the total number of impulses were held constant. Furthermore, blockade of DA autoreceptors with sulpiride stereoselectively increased the release of DA while decreasing the release of NT. These data suggest that the release of coexistent molecules (DA and NT) from mesocortical neurons can be influenced by physiological and pharmacological factors such that under certain conditions simultaneous or differential release may occur.
Rod bipolar cells in the macaque monkey retina: immunoreactivity and connectivity
Authors: Grunert U , Martin PR
Published: March 2018

Rod bipolar cells in the macaque monkey retina were labeled by three antibodies: an antibody against the alpha- and beta-subspecies of protein kinase C (PKC), a polyclonal antiserum against the L7 protein from mouse cerebellum, and a monoclonal antibody against rabbit olfactory bulb (MAb 115A 10). The MAb 115A10 antibody also labeled some cone bipolar and some amacrine cells. The antibody against PKC was used to study the synaptic connectivity of rod bipolar cells. Reconstructions of 28 rod spherules showed that usually two and up to four rod bipolar processes invaginate each rod spherule. Six rod bipolar axons in the inner plexiform layer were reconstructed; they all showed the same pattern of connectivity. Synaptic output at rod bipolar dyads usually was onto two amacrine cell profiles: one that resembled the All amacrine cell and another that frequently made a reciprocal synapse. Rod bipolar cells did not contact ganglion cells. Synaptic input to rod bipolar cells came from reciprocal amacrine cells at dyads and other amacrine cells. In these respects, the rod pathway in the monkey is very similar to that described in cat and rabbit. The density of rod bipolar cells was determined and compared with the density of rods. There is a maximum of 15,000–20,000 rod bipolar cells/mm2 at 1–3 mm eccentricity, close to where rod density is maximum. Rod density is 10 times higher than rod bipolar cell density within 2 mm of the fovea, and 30 times higher at 15 mm eccentricity. This change in relative density is compensated by an increase in the number of rods contacted by individual rod bipolar cells (seen in Golgi-stained whole-mount retina) so that the number of rod bipolar terminal boutons in each rod photoreceptor remains relatively constant with changing eccentricity. We estimate that each rod bipolar cell is contacted by about 20 rods at 2–4 mm eccentricity and about 60 rods at 6–7 mm eccentricity.
Protein kinase C alteration is an early biochemical marker in Alzheimer's disease
Authors: Masliah E , Cole GM , Hansen LA , Mallory M , Albright T , Terry RD , Saitoh T
Published: March 2018

Neuritic (senile) plaques are a hallmark of the pathology found in the brain of patients afflicted with Alzheimer's disease (AD). Neuritic plaques have been considered to be composed of an amyloid core surrounded by dilated neurites, although the use of anti-beta/A4- protein antibody revealed the presence of diffuse plaques without a nuclear-like central mass or surrounding paired helical filament (PHF)- containing neuritic components. The presence of diffuse plaques without PHF-containing neuritic components strongly suggests that the formation of amyloid precedes the degeneration of neurites that surround amyloid. Diffuse plaques are thus considered to be an early marker of AD pathology. In this article, we report that diffuse plaques, possible markers of early AD pathology, are immunostained with anti-protein kinase C(beta II) [anti-PKC(beta II)] antibodies. The PKC(beta II)- immunoreacting components of the diffuse plaques extend from neurons embedded in the plaques. Immunoelectron microscopy of diffuse and mature neuritic plaques shows that PKC(beta II)-like immunoreactivity in the plaques is closely associated with membranous structures of fine neuronal processes apposed to the amyloid fibers. These fine neuronal processes are distinct from classical neurites found typically in mature neuritic plaques. Furthermore, biochemical analysis demonstrates that PKC abnormalities, but not other AD markers (ubiquitin and A68), were found in the neocortex of clinically nondemented individuals with cortical plaques. Therefore, the PKC alteration in neurons might be involved in the early pathophysiology of AD.
The response of area MT and V1 neurons to transparent motion
Authors: Snowden RJ , Treue S , Erickson RG , Andersen RA
Published: March 2018

An important use of motion information is to segment a complex visual scene into surfaces and objects. Transparent motions present a particularly difficult problem for segmentation because more than one velocity vector occurs at each local region in the image, and current machine vision systems fail in these circumstances. The fact that motion transparency is prevalent in natural scenes, and yet artificial systems display an inability to analyze it, suggests that the primate visual system has developed specialized methods for perceiving transparent motion. Also, the currently prevalent model of physiological mechanisms for motion-direction selectivity employs inhibitory interactions between neurons; such interactions would silence neurons under transparent conditions and render the visual system blind to transparent motion. To examine how the primate visual system solves this transparency problem, we recorded the activity of direction-selective cells in the first (area V1) and in a later (area MT) stage in the cortical motion-processing pathway in behaving monkeys. The visual stimuli consisted of random dot patterns forming single moving surfaces, transparent surfaces, and motion discontinuities. We found that area V1 cells responded to their preferred direction of movement even under transparent conditions, whereas area MT cells were suppressed under the transparent condition. These data suggest a simple solution to the transparency problem at the level of area V1. More than one motion vector can be represented at a single retinal location by different subpopulations of neurons tuned to different directions of motion; these subpopulations may represent the early stage for segmenting different, transparent surfaces. The results also suggest that facilitatory mechanisms, which unlike inhibitory interactions are largely unaffected by transparent conditions, play an important role in direction selectivity in area V1. The inhibitory interactions for different motion directions for area MT neurons may contribute to a mechanism for smoothing or averaging the velocity field, computations thought to be necessary for reducing noise and interpolating moving surfaces from sparse information.
Regulation of putative muscle-derived neurotrophic factors by muscle activity and innervation: in vivo and in vitro studies
Authors: Houenou LJ , McManaman JL , Prevette D , Oppenheim RW
Published: March 2018

The normal embryonic development of spinal cord motoneurons (MNs) involves the proliferation of precursor cells followed by the degeneration of approximately 50% of postmitotic MNs during the period when nerve-muscle connections are being established. The death of MNs in vivo can be ameliorated by activity blockade and by treatment with muscle extracts. Muscle activity and innervation have been suggested to regulate the availability of putative muscle-derived neurotrophic agent(s), and MNs are thought to compete for limited amounts of these trophic agents during normal development. Thus, activity and innervation are thought to regulate MN survival by modulating trophic factor availability. We have tested this notion by examining MN survival in vivo and ChAT development in spinal cord neurons in vitro following treatments with partially purified muscle extracts from normally active, paralyzed (genetically or pharmacologically), aneural, denervated, slow tonic, and fast-twitch muscles from embryonic and postnatal animals. Extracts from active and chronically inactive embryonic avian and mouse muscles were found to be equally effective in promoting the in vivo survival of MNs in the chick embryo. Similarly, extracts from fast-twitch and slow tonic postnatal avian muscles did not differ in their ability to promote both MN survival in vivo and ChAT activity in vitro. Although aneural and control embryonic muscle extract had similar effects on ChAT development in vitro, aneural muscle extract contained somewhat less MN survival-promoting activity when tested in vivo. By contrast, denervated postnatal muscle extract was more effective in promoting both MN survival in vivo and ChAT activity in vitro than age-matched control muscle extract.
Interaction of neurotransmitter systems in the hippocampus: a study of some behavioral effects of hippocampal sympathetic ingrowth
Authors: Ayyagari V , Harrell LE , Parsons DS
Published: March 2018

Recent research has suggested that normal learning/memory may depend upon the balance between central noradrenergic and cholinergic systems. This hypothesis has particular relevance to the study of the neuronal rearrangement that follows cholinergic denervation of hippocampus. In this, peripheral noradrenergic fibers, originating from the superior cervical ganglion, grow into the hippocampus in response to lesions of the medial septal (MS) cholinergic cell bodies. To understand further the influence of hippocampal sympathetic ingrowth (HSI) on behavior, gustatory neophobia, passive avoidance (PA) learning, and open field activity were studied. Male Sprague-Dawley rats underwent one of four surgical procedures: MS lesions and sham ganglionectomy (ingrowth group; MS/HSI group), sham MS lesions and ganglionectomy (Gx group), MS lesions and ganglionectomy (no-ingrowth group; MS/Gx group), or sham MS lesions and sham ganglionectomy (CON group). Behavioral testing began 4 weeks following surgery. The time to acquire the PA task was similar among all groups; however, the initial latency to enter the dark chamber of the PA apparatus was longer, and the number of partial reentries greatest, for MS/HSI animals. Retention testing at 24 hr revealed that MS/HSI animals were significantly impaired when compared to the CON and MS/Gx groups. The MS/Gx and the CON groups demonstrated gustatory neophobia, preferring water to saccharin solution, while gustatory neophobia was absent in the MS/HSI and Gx groups. MS/HSI animals were found to be more active in the open field than the other groups. Biochemical studies revealed the expected loss of ChAT activity in the dorsal and ventral hippocampi of lesioned animals along with elevated levels of norepinephrine (NE) in the dorsal hippocampus of MS/HSI animals.
Outward currents in isolated ventral cochlear nucleus neurons
Authors: Manis PB , Marx SO
Published: March 2018

Neurons of the ventral cochlear nucleus (VCN) perform diverse information processing tasks on incoming activity from the auditory nerve. We have investigated the cellular basis for functional diversity in VCN cells by characterizing the outward membrane conductances of acutely isolated cells using whole-cell, tight-seal, current- and voltage-clamp techniques. The electrical responses of isolated cells fall into two broad categories. Type 1 cells respond to small depolarizations with a regular train of action potentials. Under voltage clamp, these cells exhibit a noninactivating outward current for voltage steps positive to -35 mV. Analysis of tail currents reveals two exponentially decaying components with slightly different voltage dependence. These currents reverse at -73 mV, near the potassium equilibrium potential of -84 mV, and are blocked by tetraethylammonium (TEA). The major outward current in Type I cells thus appears to be mediated by potassium channels. In contrast to Type I cells, Type II cells respond to small depolarizations with only one to three short- latency action potentials and exhibit strong rectification around -70 mV. Under voltage clamp, these cells exhibit a noninactivating outward current with a threshold near -70 mV. Analysis of tail currents reveals two components with different voltage sensitivity and kinetics. A low- threshold current with slow kinetics is partly activated at rest. This current reverses at -77 mV and is blocked by 4-aminopyridine (4-AP) but is only partly affected by TEA. The other component is a high-threshold current activated by steps positive to -35 mV. This current is blocked by TEA, but not by 4-AP. A simple model based on the voltage dependence and kinetics of the slow low-threshold outward current in Type II cells was developed. The model produces current- and voltage-clamp responses that resemble those recorded experimentally. Our results indicate that the two major classes of acoustic response properties of VCN neurons are in part attributable to the types of outward (potassium) conductances present in these cells. The low-threshold conductance in the Type II (bushy) cells probably plays a role in the preservation of information about the acoustic stimulus phase from the auditory nerve to central auditory nuclei involved in low-frequency sound localization.
Chronic application of NMDA decreases the NMDA sensitivity of the evoked tectal potential in the frog
Authors: Debski EA , Cline HT , McDonald JW , Constantine-Paton M
Published: March 2018

The activity-dependent mechanism that refines the topography of the retinotectal projection in frogs is mediated by the NMDA receptor. Earlier studies found that chronic treatment of the optic tectum with the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (DL- AP5) desegregated eye-specific stripes in three-eyed frogs, while chronic treatment with NMDA sharpened stripe borders (Cline et al., 1987; Cline and Constantine-Paton, 1990). We now report that this same chronic treatment with NMDA decreases the electro-physiologically measured sensitivity of the optic tectum to applied NMDA: acute application of a given concentration of NMDA decreased the evoked tectal potential to a lesser extent in animals chronically treated with NMDA than it did in normal and sham-treated animals. This is observed as a shift to the right in the NMDA dose-response curves for both the positive and negative postsynaptic components of the evoked tectal response. We believe that this decreased NMDA receptor effectiveness further restricts the intermingling of axon branches from the two eyes by limiting synapse stabilization to areas where afferent activity is most correlated. This would account for the anatomical sharpening of stripe borders (i.e., increased afferent segregation). Quantitative autoradiographic analysis of 3H-glutamate binding to NMDA receptors indicated that binding densities within the tectum did not differ between control groups and NMDA chronically treated groups. We suggest that in the experimental animals the response to NMDA may be decreased by a change in the effectiveness of individual NMDA receptors rather than by decreases in receptor number. This experimentally induced change may be analogous to naturally occurring decreases in receptor function that correlate with the end of some periods of visual plasticity in mammals.
Serotonergic facilitation of quantal release at central inhibitory synapses
Authors: Mintz I , Korn H
Published: March 2018

The teleost Mauthner (M)-cell is subjected to a powerful glycinergic inhibition that regulates its threshold for initiation of a vital escape reflex. The effects of 5-HT on this inhibition were studied in current- and voltage-clamp experiments because the M-cell and its afferents have a profuse serotonergic innervation, including axoaxonal contacts with terminals of the inhibitory interneurons. Local applications of the amine and/or of its uptake blockers markedly enhanced inhibitory currents evoked by synchronous activation of two identified presynaptic networks. In order to determine the site of this 5-HT action, we exploited the fact that in the M-cell, synaptic noise is predominantly inhibitory. Furthermore, its quantal components can be resolved providing a means to distinguish pre- and post-synaptic loci underlying variations in synaptic efficacy. As in other cell types, it consists of spontaneous exocytotic events and multiquantal responses triggered by action potentials in afferent neurons. 5-HT or its uptake blockers produced a long-lasting enhancement of this noise, manifested as a shift to the right of amplitude distribution histograms of the individual inhibitory postsynaptic currents (IPSCs) and an increase in the mean quantal content of noise. In contrast, the size of the miniature IPSC (mIPSCs) remained constant in these experiments and in another series where 5-HT was given in presence of TTX. In this case, the amine also increased the rate of occurrence of single quanta. Taken together, these data indicate that 5-HT acts presynaptically to increase the probability of evoked and spontaneous release of glycine. This conclusion was reinforced by evidence that the overall frequency of the responses in noise could be unaltered by 5-HT, indicating that the afferent firing pattern had remained constant. Extracellular recordings of the presynaptic volleys showed that action potentials were not prolonged and suggested that 5-HT closes K+ channels in the terminal membrane, leading to an increase of resistance and a larger depolarization in that region as a possible mechanism for the facilitation of release. While the enhancement of transmitter release persisted for 20 min or more, there was also a transient induction of a K+ inward-rectifying current in the M-cell. These results indicate that 5-HT increases the efficacy of inhibitory synaptic transmission in the vertebrate CNS by a presynaptic action.
Does primate motion perception depend on the magnocellular pathway?
Authors: Merigan WH , Byrne CE , Maunsell JH
Published: March 2018

This study examined the importance of the primate magnocellular retinocortical pathway in the perception of moving stimuli. A portion of the magnocellular pathway was permanently and selectively interrupted by ibotenic acid injections in the LGN of macaque monkeys. We then tested contrast sensitivity for detecting moving stimuli, as well as two indices of motion perception, contrast sensitivity for opposite direction discrimination and speed difference thresholds, in the affected portion of the visual field. Magnocellular lesions greatly reduced detection contrast sensitivity at high temporal and low spatial frequencies and had a similar effect on contrast sensitivity for opposite direction discrimination under these same stimulus conditions. Consequently, opposite direction discriminations could be made at contrast threshold, suggesting that magnocellular lesions reduced the visibility of stimuli used to test direction perception, but did not act directly on direction perception. Magnocellular lesions also elevated speed difference thresholds under some stimulus conditions. However, this deficit was reduced or eliminated by raising the contrast of the test stimulus. Together, these findings suggest that magnocellular lesions reduce the visibility of stimuli used to test motion perception but that they do not appear to alter motion perception otherwise.