bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurophysiology of magnocellular forebrain inputs to the olfactory bulb in the rat: frequency potentiation of field potentials and inhibition of output neurons
Authors: Nickell WT , Shipley MT
Published: March 2018

Basal forebrain nuclei send projections, including cholinergic fibers, to forebrain cortical targets. These systems have been associated with several important functions, but their physiological actions are poorly understood. We have studied the neurophysiological characteristics of one of these systems, the projection from the nucleus of the horizontal limb of the diagonal band (HDB) to the main olfactory bulb (MOB) in the rat. Single shocks to HDB produce modest field potentials in MOB with no detectable effect on the discharge characteristics of the principal output neurons of the MOB, the mitral cells. By contrast, continuous stimulation at 10 Hz for several seconds causes dramatic changes in the HDB field potential and mitral cell firing. During this period of stimulation, there is an initial facilitation of the field potential followed by a period of moderately reduced response amplitude that lasts a few seconds. This brief period of depression is succeeded by a sudden and marked potentiation of response amplitude and duration. This potentiated response can be maintained indefinitely by stimulation at lower frequencies than those required to initiate the potentiation effect. Coincident with the onset of the potentiated response, the spontaneous activity of the mitral cells is completely inhibited. Both the potentiation and mitral cell inhibition can be maintained indefinitely by continued stimulation at frequencies as low as 6 Hz. These observations demonstrate that magnocellular basal forebrain neurons exert powerful regulatory actions on specific neuronal populations in cortical targets.
The sequential appearance of low- and high-molecular-weight forms of MAP2 in the developing cerebellum
Authors: Tucker RP , Binder LI , Viereck C , Hemmings BA , Matus AI
Published: March 2018

Mammalian microtubule-associated protein 2 (MAP2) exists in high- molecular-weight (Mr approximately 280,000) and low-molecular-weight (Mr approximately 70,000) forms, with the latter protein being more abundant in embryonic brain homogenates than in preparations from mature brain (Riederer and Matus, 1985). In the current study, we have shown that avian MAP2 also exists as both high- (Mr approximately 260,000) and low-molecular-weight (Mr approximately 65,000) forms whose relative abundance changes during brain maturation, indicating a conserved function for these proteins during vertebrate neuronal morphogenesis. Using indirect immunohistochemistry, we have determined the cellular distribution of the high- and low-molecular-weight forms of MAP2 in the developing avian cerebellum. In the embryonic cerebellum, low-molecular-weight MAP2 is found in the external granular layer and in epithelial cells. High-molecular-weight MAP2 is found only in neurons that have commenced dendrogenesis, i.e., Purkinje cells and neurons within the internal granular layer. Thus, low-molecular-weight MAP2 is not only more abundant in embryonic nervous tissue than in the adult, but it also appears in glia and in differentiating neurons before the high-molecular-weight form. We have also shown that in the mature cerebellum high-molecular-weight MAP2 cannot be detected with monoclonal antibodies or polyclonal antisera in Purkinje cell dendrites. Polyclonal antisera against the regulatory subunit of the cAMP-dependent protein kinase, which is associated with MAP2 in the Purkinje cell dendrites of the rat, also fail to stain Purkinje cell dendrites in the mature quail cerebellum. This suggests that high- molecular-weight MAP2 may be necessary for the establishment of dendrites but is not necessary for the maintenance of dendritic form.
Presynaptic long-term facilitation at the crayfish neuromuscular junction: voltage-dependent and ion-dependent phases
Authors: Wojtowicz JM , Atwood HL
Published: March 2018

Long-term facilitation (LTF) of synaptic transmission was investigated in the crayfish opener muscle to determine the factors necessary for its induction and expression. LTF was induced without action potentials by intracellular depolarization of presynaptic nerve terminals. Following induction, the synaptic transmission was enhanced by about 80% for a period of several hours. Intracellular recordings from pre- and postsynaptic cells, combined with ionic and pharmacological tests, permitted dissection of LTF into 2 phases: an initial tetanic phase that depended on the presence of both sodium and calcium ions and a subsequent long-lasting phase. This latter long-lasting enhancement of synaptic transmission was induced by repeated depolarizations of synaptic terminals but did not depend on the influx of sodium or calcium ions or on intracellular release of calcium ions. Both tetanic and long-lasting phases of LTF are attributable to activity of a single neuron, i.e., they are homosynaptic phenomena. Furthermore, LTF is associated with an increase of quantal release, whereas the size of quanta remains unchanged. During the long-lasting phase of LTF, the nerve terminal releases more transmitter for a given depolarization than before induction of LTF. Thus, the locus of LTF is presynaptic. Our findings suggest the presence of a voltage-dependent mechanism in the presynaptic membrane different from voltage-gating of Na or Ca channels. Such a mechanism may be important in the establishment of long-lasting synaptic changes at the crayfish neuromuscular junction and perhaps in other neural systems.
Inhibition of voltage-gated K channels in synaptosomes by sn-1,2- dioctanoylglycerol, an activator of protein kinase C
Authors: Colby KA , Blaustein MP
Published: March 2018

Tracer efflux studies were used to determine the effect of activation of protein kinase C on K channel function in rat brain synaptosomes. Hippocampal synaptosomes were treated with sn-1,2-dioctanoylglycerol (diC8), a synthetic diacylglycerol (DG) analog that activates protein kinase C. DiC8 inhibited depolarization-induced 86Rb efflux through voltage-gated K channels but did not affect the component of efflux corresponding to Ca-activated K channels. In time-course experiments, diC8 inhibited two components of 86Rb efflux: efflux through a rapidly inactivating, voltage-gated K channel (responsible for the “A” current) and that through a slowly inactivating, voltage-gated K channel (believed to be the “delayed rectifier”). Experiments with specific blockers of these voltage-gated K channels supported this observation. Inhibition of K-stimulated 86Rb efflux by diC8 was time dependent: at least 15 sec of preincubation was required before the effect could be observed. The effect of diC8 was concentration dependent: 50 microM diC8 produced a half-maximal inhibition of K-stimulated 86Rb efflux. The idea that the inhibition of synaptosome K channels by diC8 resulted from activation of C kinase was supported by pharmacological evidence. The action of diC8 was mimicked by 1-oleoyl-2-acetylglycerol, another DG analog that activates protein kinase C, but not by deoxy-diC8, a DG analog that does not activate C kinase. Inhibition of C kinase by sphingosine or H-7 prevented the diC8 effect. These studies demonstrate that synaptosomes are a good model in which to study modulation of mammalian CNS K channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Habituation and dishabituation of a cleaning reflex in normal and mutant Drosophila
Authors: Corfas G , Dudai Y
Published: March 2018

Upon tactile stimulation of its thoracic bristle(s), Drosophila cleans with a patterned set of leg movements the field covered by the stimulated bristles. We demonstrate that this cleaning reflex undergoes habituation and dishabituation. Repeated monotonous stimulation of the bristles by controlled air puffs leads to decrement, and finally to disappearance, of leg response. Spontaneous recovery of the response takes place in a time-dependent manner. Restoration of response can also be obtained by application of a high-frequency stimulus directed to other bristles. A mutant, rut, which is defective in learning and in adenylate cyclase activity, can habituate and dishabituate, but habituation is abnormally short-lived. As opposed to both nonassociative and associative learning paradigms used in Drosophila to date, the cleaning reflex lends itself to some aspects of cellular analysis, since single sensory neurons that mediate the input and motor neurons that mediate the behavioral output are identifiable. The modified reflex should therefore be useful in establishing the effects of single gene mutations that affect behavioral plasticity on the development and properties of identified neurons that contribute to discrete modifiable behaviors.
Effects of locus coeruleus lesions on auditory, long-latency, event- related potentials in monkey
Authors: Pineda JA , Foote SL , Neville HJ
Published: March 2018

It has previously been demonstrated that monkeys exhibit certain event- related potential (ERP) components showing latency, polarity, and contingency similarities to those observed in humans. In the present study, monkey P300-like components were studied in order to evaluate the hypothesis that the noradrenergic locus coeruleus (LC) system participates in their generation or modulation. ERPs were recorded from untrained squirrel monkeys (Saimiri sciureus) twice a week for 4 weeks before and after bilateral LC lesions and interruption of dorsal bundle (DB) fibers. Stimuli consisted of 2 and 6 kHz tone pips (40 msec duration, 60 dB above nHL) presented once a second in random order. In most sessions, one tone constituted 90% of the stimuli and the other tone 10%, while in some sessions tones were made equiprobable to test the effects of manipulating stimulus probability. LC and DB lesions were made by first localizing the nucleus and creating an electrolytic lesion. Then, the electrode was placed at the anterior pole of the nucleus and a knife cut effected. The extent of damage to LC perikarya and ascending axons was assessed by reconstructing lesions from Nissl- stained sagittal sections through the brain stems. The effect of lesions on cortical noradrenergic axons was immunohistochemically verified utilizing antisera directed against dopamine-B-hydroxylase and tyrosine hydroxylase to label noradrenergic and dopaminergic axons, respectively. The prelesion ERP results replicated previous findings of P300-like components recorded in response to low-probability tones. The postlesion ERP data indicated that following damage to LC cell bodies, combined with interruption of histochemically detectable ascending noradrenergic axons, monkey P300-like potentials exhibited decreased areas, altered brain-surface distribution, and reduced sensitivity to stimulus probability. The correlation between the extent of cell body lesions and percentage reduction in the magnitude of P300-like responses was significant. However, interruption of DB fibers alone did not have similar effects. Neither type of lesion had any effect on amplitudes, latencies, or brain-surface distributions of P52, P172, or N250–900. There was, however, a significant effect on N106. Stimulus probability effects on the frontally distributed P52 and N106 were not altered by the lesions. These data support the hypothesis that the integrity of the LC nucleus and its ascending fibers is important in the generation and modulation of surface-recorded P300-like activity.
Topographical organization of the entorhinal projection to the dentate gyrus of the monkey
Authors: Witter MP , Van Hoesen GW , Amaral DG
Published: March 2018

The topographic organization of the projections from the entorhinal cortex to the dentate gyrus in the macaque monkey was studied with anterograde and retrograde tracing methods. Injections of WGA-HRP or the fluorescent retrograde tracers, Fast blue and Diamidino yellow, were placed at various levels along the rostrocaudal axis of the dentate gyrus and hippocampus. In 5 experiments the fluorescent dyes were injected at 2 rostrocaudal levels of the same dentate gyrus. Labeled neurons were observed mainly in layers II and III of the entorhinal cortex, though some were also seen in layers V and VI. The labeled layer II cells resulting from each of the tracer injections were located throughout much of the rostrocaudal extent of the entorhinal cortex, though they tended to have a more limited distribution in the transverse or mediolateral axis. Injections of retrograde tracers located caudally in the dentate gyrus resulted in a rostrocaudally oriented zone of labeled cells that was situated laterally in the entorhinal cortex adjacent to the rhinal sulcus. The zone of labeled cells was not oriented strictly parallel to the rhinal sulcus since at caudal levels it extended medially to encompass the full transverse extent of the most caudal portion of the entorhinal cortex. When injections were placed more rostrally in the dentate gyrus and hippocampus, the rostrocaudally oriented zone of labeled cells was situated more medially in the entorhinal cortex. Anterograde tracing experiments using 3H-amino acid injections into different rostrocaudal and mediolateral positions of the entorhinal cortex confirmed the organization demonstrated by the retrograde tracers and further indicated that the entorhinal fibers terminate in the outer two-thirds of the molecular layer of the dentate gyrus. Unlike in the rat, where the entorhinal termination zone in the molecular layer is clearly bilaminate, projections from all portions of the entorhinal cortex appeared to terminate more diffusely throughout the outer two-thirds of the molecular layer. The results of the present study indicate that rostrocaudally oriented zones of cells that cut across several cytoarchitectonic subdivisions of the entorhinal cortex give rise to topographically organized projections to the dentate gyrus. Cells located laterally in the entorhinal cortex project to caudal levels of the dentate gyrus, whereas progressively more medially situated cells project to progressively more rostral parts of the dentate gyrus.
In situ hybridization analysis of myelin gene transcripts in developing mouse spinal cord
Authors: Jordan C , Friedrich V , Dubois-Dalcq M
Published: March 2018

We analyzed the location and abundance of transcripts for the 4 CNS myelin protein genes, myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), and 2′,3′-cyclic nucleotide phosphohydrolase (CNP), in the mouse cervical spinal cord from the time of rapid myelination until adulthood (8–45 d). In the white matter, maximal levels of transcripts were found for each of the myelin genes at the peak of myelination (8 d). Total MBP and PLP mRNAs stayed high until 20 d and showed a minor decrease thereafter. In contrast, MAG and the MBP exon 2 containing transcripts (coding for the 21.5 and 17 kDa MBP isoforms) decreased sharply between 8 and 20 d, suggesting that high levels of these transcripts are needed primarily during the initiation of myelination. CNP transcripts were less abundant, maintained high expression until 20 d, and then decreased sharply. PLP, MAG, and CNP transcripts were clustered in the oligodendrocyte cell body, while MBP mRNAs were scattered throughout the cell body and processes. In contrast to the white matter, all these myelin specific transcripts in the gray matter showed a marked increase from 8 to 20 d, as did the number of oligodendrocytes identified by CNP immunostaining. MAG transcripts were found in white matter and in satellite and other oligodendrocytes of the gray matter but not in neurons identified by their expression of neurofilament transcripts. The results of our quantitative in situ hybridization study are in good agreement with those of previous molecular studies and provide new information on the cellular and topographic distribution of myelin- specific mRNAs during myelination.
Neuroleptic-sensitive binding sites in the nigrostriatal system: evidence for differential distribution of sigma sites in the substantia nigra, pars compacta of the cat
Authors: Graybiel AM , Besson MJ , Weber E
Published: March 2018

The sigma site is a recently described binding site to which dextrorotary isomers of certain psychotomimetic benzomorphans bind specifically. Classical and nonclassical neuroleptics also have high affinity for the sigma site, including neuroleptics known to bind to the D2 dopamine receptor. The affinity of some D2-binding neuroleptics for the sigma site has raised the possibility that certain important effects of antipsychotic drugs may relate to the sigma site. Left unresolved has been the question of how these actions could relate to dopaminergic systems. To explore this issue we carried out an autoradiographic binding study of the distribution of the sigma- selective ligand 3H-DTG in the nigrostriatal system. We report here that haloperidol-displaceable 3H-DTG binding sites are densely concentrated in an anatomically discrete subdivision of the cat's substantia nigra pars compacta. This zone, identifiable as the striosome-projecting densocellular zone of the pars compacta, also shows heightened D2-related ligand binding but has reduced D1-related ligand binding relative to other parts of the nigral complex. This evidence suggests that sigma-mediated interactions with dopaminergic systems may occur in the substantia nigra pars compacta and that the functional effects of these interactions may influence the nigrostriatal projection to striosomes differentially.
Neuropsychological evidence for multiple implicit memory systems: a comparison of Alzheimer's, Huntington's, and Parkinson's disease patients
Authors: Heindel WC , Salmon DP , Shults CW , Walicke PA , Butters N
Published: March 2018

The performances of patients with dementia of the Alzheimer type (DAT), patients with Huntington's disease (HD), and demented and nondemented patients with Parkinson's disease (PD) were compared on 2 tests of implicit memory that do not require the conscious recollection of prior study episodes: (1) a pursuit-rotor motor learning task and (2) a lexical priming test. The HD patients were found to be impaired on the motor learning but not the lexical priming task, whereas the DAT patients evidenced the opposite relationship on these tasks. The demented, but not the nondemented, PD patients were found to be impaired on both tests of implicit memory. For both the HD and PD patients, deficits on the motor learning task correlated significantly with severity of dementia but not with level of primary motor dysfunction. The noted double dissociation between HD and DAT patients indicates that different forms of implicit memory, all of which are intact in amnesia, are dependent upon distinct neuroanatomic systems. Motor skill learning may be mediated by a corticostriatal system, whereas verbal priming may depend upon the integrity of the neocortical association areas involved in the storage of semantic knowledge. The results for the PD patients suggest that the demented PD patients have endured damage to the neurologic systems subserving both motor learning and lexical priming.
Two distinct mechanisms, differentially affected by excitatory amino acids, trigger GABA release from fetal mouse striatal neurons in primary culture
Authors: Pin JP , Bockaert J
Published: March 2018

The mechanisms leading to Ca2+-dependent and Ca2+-independent GABA release were studied on highly purified striatal neurons developed in primary culture. Ca2+-dependent GABA release, which represents about 75% of the 56 mM K+ effect was totally inhibited when striatal neurons were first exposed to tetanus toxin (TnTx) (10 micrograms/ml) for 24 hr. The K+ effect was potentiated when 1 mM nipecotic acid (an inhibitor of the GABA uptake system) was added during the stimulation period or when Na+ was replaced by Li+. However, no difference in the GABA release measured under high-K+ conditions was observed after a 22 min preincubation of the neurons in a medium containing nipecotic acid or Li+. Replacement of Cl- ions by SO4(2-) did not modify K+-evoked GABA release. Ca2+-independent GABA release was stimulated by veratridine (20 microM), ouabain (3 mM), and monensin (20 microM), as well as the excitatory amino acids glutamate (100 microM), N-methyl-D- aspartate (100 microM), quisqualate (10 microM), and kainate (1 mM), drugs known to increase intracellular Na+ concentration. The veratridine- or glutamate-evoked GABA release was neither inhibited when intracellular Ca2+ content was reduced by more than 90% nor by treatment of the neurons to TnTx. However, the Ca2+-independent GABA release elicited by veratridine was inhibited by preincubation of the neurons in a medium containing 1 mM nipectotic acid and in a medium containing Li+ instead of Na+ or SO4(2-) instead of Cl-. These results strongly suggest that 2 different GABA release mechanisms exist in striatal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Interlaminar and lateral excitatory amino acid connections in the striate cortex of monkey
Authors: Kisvarday ZF , Cowey A , Smith AD , Somogyi P
Published: March 2018

The intrinsic excitatory amino acid pathways within the striate cortex of monkeys were studied by autoradiographic detection of retrogradely labeled somata following microinjections of D-3H-aspartate (D-3H-Asp) into different layers. The labeled amino acid was selectively accumulated by subpopulations of neurons and, to a small extent, by glial cells, the latter mainly in the supragranular layers. Immunocytochemical detection of neurons containing GABA showed that, apart from a few cells exclusively in layer I, GABAergic neurons do not accumulate D-3H-Asp. Several lines of evidence suggest that D-3H-Asp uptake occurred only at nerve terminals; thus, the pattern of perikaryal labeling allowed the delineation of interlaminar and lateral projections. Neurons in layer I probably project laterally, and layer I receives wide-ranging projections from layer IVB and layer V from cells up to 1300 microns laterally. Some neurons in layer II send a focused projection to lower layer VI. Some neurons in layers II/III project up to 1 mm laterally within their own layer, but relatively few neurons can be labeled in these projections. Similarly, in layers II/III few neurons can be retrogradely labeled from layers V and upper VI, and this projection is organized such that cells closer to the pia project deeper in layer V/VI. The connections of layer IVA could not be revealed separately because of the difficulty of confining injections to this thin sublamina. Neurons in layer IVB project up to 1300 microns within IVB itself. A small number of cells from IVB also project to layers III, IVC-alpha, V, and VI with much more restricted lateral spread. Neurons in upper IVC-alpha send axons to layer IVB with at least 600–800 microns lateral spread. Neurons in lower IVC-alpha/upper IVC-beta project to layer III with at least 300–500 microns lateral spread. The bottom 50–80 microns of layer IVC-beta contains neurons with a very focused projection, apparently exclusively to the layer III/IVA border region. Both layers IVC alpha and beta have rich connections within themselves, the beta sublayer having more restricted lateral connections. Some neurons in layer IVC-beta give a laterally restricted small input to layers IVC-alpha and IVB. Both IVC-alpha and - beta project to layers V and VI, and these projections are spread at least 400 microns laterally. Neurons in layer V project to all layers, but the projection to layers I-III and within layer V itself spread much further laterally than the projections to layers IV and VI.(ABSTRACT TRUNCATED AT 400 WORDS)
Opioids induce convulsions and wet dog shakes in rats: mediation by hippocampal mu, but not delta or kappa opioid receptors
Authors: Lee PH , Obie J , Hong JS
Published: March 2018

The opioid receptor subtypes and brain regions involved in eliciting convulsions and wet dog shakes (WDS) were studied by testing different opioid receptor selective agonists in unanesthetized rats. Selective mu agonists, [NMe-Phe3-D-Pro4]-morphiceptin (PL017) and [D-Ala2-N-methyl- Phe3-Gly5-ol]-enkephalin, induced convulsions and WDS when unilaterally injected into the ventral hippocampus. [D-Ala2,D-Leu5]-enkephalin (DADLE), a mixed mu and delta agonist, also elicited such behavioral changes, but its effect was less potent than the selective mu agonists. DADLE-induced WDS were dose dependent, and both convulsions and WDS were antagonized by the irreversible mu receptor antagonist, beta- funaltrexamine, but not by the selective delta receptor antagonist, ICI- 174,864. Treatment with the selective delta agonist [D-Pen2,5]- enkephalin or the selective kappa agonists U-50,488H, dynorphin-A amide, or dynorphin-A(1–8) did not produce convulsions or WDS. The injection of a high dose of PL017 intraventricularly or into other brain regions such as the dorsal hippocampus, frontal cortex, striatum, and amygdala did not produce convulsions or WDS, therefore suggesting the ventral hippocampus is an important site for the expression of opioid-induced convulsions and WDS. These results suggest that opioid- induced convulsions and WDS are mediated exclusively by mu but not delta or kappa opioid receptors in the ventral hippocampus.
Lamprey neurofilaments combine in one subunit the features of each mammalian NF triplet protein but are highly phosphorylated only in large axons
Authors: Pleasure SJ , Selzer ME , Lee VM
Published: March 2018

Compared with heteropolymeric assemblies of neurofilament (NF) triplet proteins in mammalian NFs, lamprey (Petromyzon marinus) NFs are homopolymers of 180 kDa subunits (NF180). We describe unique features of lamprey NF180 that distinguish it as a prototype of vertebrate NF subunits. These features may underlie key functions subserved by the earliest vertebrate NFs. Lamprey NF180 displays properties common to all intermediate filament (IF) proteins, but it also exhibits features that distinguish the mammalian triplet of NF subunits from all other IF proteins. For example, digestion of lamprey NF180 with chymotrypsin produces an insoluble 40 kDa core unit and releases a soluble fragment intermediate in size (140 kDa) to the carboxy-terminal (sidearm) extensions of the 2 high-molecular-weight (Mr) mammalian NF subunits. The core unit contains epitopes similar to those in the core of each mammalian NF triplet protein, while the soluble fragment contains other determinants similar to those in the sidearms of the 2 high-Mr mammalian NF polypeptides. Like these polypeptides, the immunological properties of some NF180 peripheral determinants were strongly affected by their phosphorylation state. Indeed, NF180 shares immunological similarities with the multiphosphorylation repeat domains in the high- Mr mammalian NF subunits. Further similarities with mammalian NF proteins include the preferential expression of poorly phosphorylated NF180 isoforms and of phosphate-dependent NF180 epitopes in axons of all sizes, and the restriction of nonphosphorylated NF180 isoforms to neuronal perikarya. In marked contrast to mammals, however, the most heavily phosphorylated isoforms of NF180 were expressed exclusively in large-diameter axons. We conclude that the single subunit forming lamprey NFs exhibits the essential features of mammalian NFs, i.e., a filament-forming core and a carboxy-terminal extension with a multiphosphorylation site. Further, the sharp restriction of heavily phosphorylated NF180 to large axons suggests that multiphosphorylation domains were acquired during evolution to permit larger axon diameters and faster conduction velocities.
Amplitude fluctuations in small EPSPs recorded from CA1 pyramidal cells in the guinea pig hippocampal slice
Authors: Sayer RJ , Redman SJ , Andersen P
Published: March 2018

EPSPs have been evoked in CA1 pyramidal cells by (1) activation of single CA3 neurons (unitary EPSPs), and (2) low-intensity stimuli to the CA1 stratum radiatum. Five unitary EPSPs were obtained; their mean peak amplitudes ranged from 85 to 275 microV and 3 of the 5 showed fluctuations in amplitude that were too great to be attributed to baseline noise. After subtraction of the variance due to the noise, these EPSPs had coefficients of variation much higher than those reported for variability in the quantal EPSP in other preparations. These results suggest that intermittent transmitter release is a major cause of EPSP amplitude fluctuation at this synapse. A noise deconvolution technique based on a nonrestrictive model of transmitter release was applied to the EPSPs obtained in this study. For 2 of the EPSPs evoked by stratum radiatum stimulation, the amplitudes fluctuated between discrete values that were sufficiently separated with respect to the noise to be resolved by the deconvolution procedure. Quantal increments of 224 and 193 microV were determined for the 2 EPSPs.
Expression of GAP-43, a rapidly transported growth-associated protein, and class II beta tubulin, a slowly transported cytoskeletal protein, are coordinated in regenerating neurons
Authors: Hoffman PN
Published: March 2018

GAP-43 is a membrane-associated phosphoprotein enriched in elongating axons (Meiri et al., 1986; Skene et al., 1986). After an axon has been interrupted by cutting or crushing a nerve (axotomy), the portion of the axon disconnected from the cell body (distal stump) degenerates and is replaced by the outgrowth (elongation) of regenerating sprouts arising from the proximal stump. Previous studies have shown that increased amounts of pulse-labeled GAP-43 undergo fast axonal transport in regenerating neurons (Benowitz et al., 1981; Skene and Willard, 1981 a, b). Using hybridization with a cloned cDNA probe, I now show that mRNA levels for GAP-43 increase in lumbar sensory neurons of rat after regeneration is initiated by crushing the sciatic nerve; the relatively high levels of GAP-43 mRNA in regenerating neurons are comparable to those in the developing neurons of 5-d-old animals. I further demonstrate that the induction of GAP-43 expression in regenerating neurons coincides temporally with an increase in mRNA levels for class II beta tubulin (Hoffman and Cleveland, 1988), suggesting that the expression of these proteins is closely coordinated during axonal elongation.
Motor activity in the isolated spinal cord of the chick embryo: synaptic drive and firing pattern of single motoneurons
Authors: O'Donovan MJ
Published: March 2018

The cellular mechanisms underlying embryonic motility were investigated using intracellular recording from motoneurons and electrotonic recording from muscle nerves during motor activity generated by an isolated spinal cord preparation of 12- to 15-d-old chick embryos. DC- coupled recordings from sartorius (a flexor) and femorotibialis (an extensor) muscle nerves revealed that both sets of motoneurons were depolarized at the same time in each cycle even when the motoneurons fired out of phase. Sartorius motoneurons fired briefly on the rising phase of the depolarization and then stopped firing before discharging a second burst of spikes as the depolarization decayed. By contrast, femorotibialis motoneurons fired at the peak of their depolarization, which was coincident with the interruption in sartorius activity. Intracellular recordings from antidromically identified motoneurons confirmed that flexor and extensor motoneurons were depolarized at the same time during each cycle of activity. The discharge of femorotibialis motoneurons, and others presumed to be extensors, followed changes in membrane potential so that maximal firing occurred during peak depolarization. The relationship between discharge and membrane potential was different in sartorius motoneurons (and in others presumed to be flexors) because they fired briefly on the rising phase of the depolarization and then stopped firing during peak depolarization. In some of these cells firing resumed as the membrane potential decayed back to rest. Intracellular injection of depolarizing current into sartorius motoneurons during motor activity reversed the direction of the membrane potential change from depolarizing to hyperpolarizing during the pause in sartorius discharge. In addition, the discharge evoked by the depolarizing current was blocked during the reversed part of the synaptic potential revealing its inhibitory nature. The occurrence of the IPSP was accompanied by a large reduction in motoneuronal input impedance. Injection of depolarizing current steps into motoneurons produced steady firing with no evidence of a pause in discharge, indicating that the depolarization accompanying synaptic activity was not responsible for the pause in firing of flexor motoneurons. These results suggest that flexor and extensor motoneurons receive a similar depolarizing drive from a common set of excitatory premotor interneurons. The alternating pattern of flexor and extensor discharge is produced, in part, by the timing of a depolarizing IPSP coincident with extensor activity that silences flexor discharge.(ABSTRACT TRUNCATED AT 400 WORDS)
The effects of dephosphorylation on the structure of the projections of neurofilament
Authors: Hisanaga S , Hirokawa N
Published: March 2018

Carboxy-terminal tail domains of larger molecular mass subunits (NF-M and NF-H) of neurofilaments (NFs), which are the highly phosphorylated moieties, were observed as thin flexible filaments projecting from NF core filaments by rotary shadowing (Hisanaga and Hirokawa, 1988). Dephosphorylation of NFs has been suspected to affect the structures and the functions of the carboxy-terminal tail projections. We report here the effects of the dephosphorylation on the structure of NFs studied by electron microscopy. (1) The structures of carboxy-terminal tail projections after dephosphorylation were compared with those of the control NFs by low-angle rotary shadowing. This was examined with 2 samples; the isolated neurofilaments and the short filaments assembled from NF-H. Both the dephosphorylated NFs and the short filaments showed many projections laterally extending from core filaments similar to those observed in the control samples. (2) With respect to the structure of NF in physiological solution, the density of NFs in the precipitates was examined by thin-section electron microscopy. No difference in the density was noted between control and dephosphorylated NFs. (3) The ability to form cross-bridges in vitro was examined by quick-freeze, deep-etch electron microscopy. The structure and frequency of cross-bridges appeared to be similar in both control and dephosphorylated NFs. (4) Phosphate determination revealed that about 90% of the phosphate groups of NF-H subunit were removed by treatment with E. coli alkaline phosphatase. These results indicated that the dephosphorylation of NF did not affect the structure and the ability to form cross-bridges of the carboxy-terminal tail projections in vitro.
Cortical areas involved in OKN and VOR in cats: cortical lesions
Authors: Tusa RJ , Demer JL , Herdman SJ
Published: March 2018

Eye movements evoked by optokinetic and vestibular stimulation were measured by scleral search coil before and up to 8 weeks after unilateral cortical lesions in 11 cats. During both monocular and binocular viewing conditions, several deficits in the velocity-storage component of optokinetic nystagmus (OKN) were found. At low target velocities, the final steady-state slow-phase eye velocity and the peak value of optokinetic afternystagmus (OKAN) were reduced for slow phases towards the side of the lesion. At high target velocities OKN and OKAN were no longer elicited. The time constant of OKAN was also reduced for slow phases towards the side of the lesion. These deficits in OKN and OKAN were quantitatively similar in cats with large cortical (LC) lesions involving all known visual areas and in cats with suprasylvian (SS) lesions involving areas 21a, 21b, PMLS, and VLS. Ablation of areas 17 and 18 alone had no effect, but when combined with section of the corpus callosum (17/18+CC) resulted in a qualitatively similar but less severe deficit as the LC and SS lesions. By 3 weeks postoperatively, OKN recovered to near preoperative values in cats with SS lesions. Vestibular adaptive capabilities were impaired during the duration of the study in cats with LC, SS, and 17/18+CC lesions. Cats with these lesions could not normally increase VOR gain for slow phases directed ipsilateral to the lesion, and following vestibular adaptation most of these cats developed persistent asymmetries in VOR gain and VOR time constants. These results can be better conceptualized using a mathematical model of the vestibulo-ocular and optokinetic system adapted from Robinson (1977). This model contains a single positive- feedback velocity storage loop common to the VOR and OKN systems and a retinal-slip velocity nonlinearity. Our results suggest that SS cortex improves the retinal-slip nonlinearity feeding into the velocity- storage system by extending its range and increasing its gain. The SS cortex depends in part upon areas 17 and 18 either directly, or indirectly via the corpus callosum, for processing of high retinal-slip velocities. Cerebral cortex is also involved in increasing the gain of the velocity-storage loop during vestibular adaptation for ipsilaterally directed slow phases.
Gating scheme for single GABA-activated Cl- channels determined from stability plots, dwell-time distributions, and adjacent-interval durations
Authors: Weiss DS , Magleby KL
Published: March 2018

To study the gating of a GABA-activated Cl- channel, currents from single channels activated by 1.0 microM GABA were examined in patches of membrane excised from cultured chick cerebral neurons. The distributions of open and shut interval durations were each described by the sum of 3 exponential components, suggesting that the channel normally enters at least 3 open and 3 shut states. Five different 6- state gating schemes were found that could describe, all equally well, the observed distributions of open and shut interval durations. Plots of the mean duration of open intervals adjacent to shut intervals of specified durations revealed that, on the average, openings of brief duration were adjacent to closings of long duration. This observation indicated 2 or more independent transition pathways between the open and shut states. Examination of the distributions of open intervals adjacent to shut intervals of specified durations revealed that the time constants of the exponential components describing these conditional open-interval distributions were independent of the durations of the adjacent shut intervals. In contrast, the areas changed in a manner consistent with open states of briefer mean lifetimes typically making transitions to shut states of longer mean lifetimes. Four of the 5 gating schemes considered were rejected because they did not predict the relationship between adjacent intervals or because they predicted that the channel should switch between 2 gating modes with markedly different mean open and shut times, which was not a characteristic of the experimental data. The single remaining kinetic scheme could account for the observed kinetic properties of the GABA channel.
Nonlinear summation of M- and L-cone inputs to phasic retinal ganglion cells of the macaque
Authors: Lee BB , Martin PR , Valberg A
Published: March 2018

We have studied the responses of ganglion cells in the macaque retina to stimuli that alternate in color. With most color combinations, the phasic retinal ganglion cells, which sum input from M- and L-cones in both center and surround, showed a response with twice the alternation frequency at equal luminance. This frequency doubling was directly related to the degree to which the M- and L-cones were stimulated out- of-phase with one another, and thus varied with the wavelength combinations used. It was absent with wavelength combinations that lay along tritanopic confusion lines, when at equal luminance the M- and L- cones are not modulated. Such a frequency-doubled response is evidence for a nonlinearity at or before M- and L-cone summation. The effect became much smaller or was abolished when the receptive field center alone was stimulated, indicating that its mechanism lies in the surround or in a center-surround interaction. Also, it was much more marked at high luminance levels, being almost absent at retinal illuminances below 100 td. Its origin is not clear, but it seems to derive more from the L- than the M-cone. The results imply that phasic cells, through this nonlinearity, could respond to the red-green equal luminance borders used in some psychophysical experiments.
Rapid induction of the major embryonic alpha-tubulin mRNA, T alpha 1, during nerve regeneration in adult rats
Authors: Miller FD , Tetzlaff W , Bisby MA , Fawcett JW , Milner RJ
Published: March 2018

The mRNAs for 2 isotypes of alpha-tubulin, termed T alpha 1 and T26, are differentially regulated in the developing rat nervous system. T alpha 1 alpha-tubulin mRNA is expressed at high levels when neurons extend processes whereas T26 mRNA is expressed constitutively (Miller et al., 1987b). We have examined the expression of these 2 alpha- tubulin mRNAs in regenerating facial and sciatic motor neurons of the rat using Northern blot and in situ hybridization analyses. T alpha 1 alpha-tubulin mRNA is rapidly induced in axotomized motor neurons of the facial nerve: increased levels of mRNA are detectable 4 hr after a lesion is made 1.5 cm distal to the neuronal cell bodies. T alpha 1 mRNA levels are highest from 3–7 d postcrush and decline slowly to control levels following functional reinnervation of facial muscles. In contrast, T26 mRNA levels remain constant throughout the regeneration process. Total alpha-tubulin mRNA levels do not change until 1 d postaxotomy; otherwise the changes in expression are similar to T alpha 1 mRNA, although the relative increase is not as great. Enhanced T alpha 1 alpha-tubulin mRNA expression also occurs in motor neurons of crushed or tied sciatic nerve. Ligature or crush of the sciatic nerve leads to approximately the same peak in the expression of T alpha 1 mRNA at 7–15 d postaxotomy. Following the facial nerve transection, under conditions in which reinnervation is prevented, T alpha 1 alpha- tubulin mRNA levels remain elevated significantly longer than when the nerve is crushed. Taken together, the data indicate that T alpha 1 alpha-tubulin mRNA is rapidly induced following neuronal axotomy, remains elevated during the period of axonal regrowth, and is subsequently down-regulated at the approximate time of target contact. These results are reminiscent of changes in T alpha 1 mRNA that occur during neuronal development. This growth-associated pattern of T alpha 1 gene expression can be modified by inhibiting appropriate regeneration of the damaged nerve.
Cooperation and competition during development: neonatal lesioning of the superior cervical ganglion induces cell death of trigeminal neurons innervating the cerebral blood vessels but prevents the loss of axon collaterals from the neurons that survive
Authors: O'Connor TP , van der Kooy D
Published: March 2018

In the adult rodent trigeminal ganglion there is a period of postnatal cell death in the population of cells with axons innervating the middle cerebral artery (O'Connor and van der Kooy, 1986b). The superior cervical ganglion (SCG) also has a projection to the middle cerebral artery (MCA; Mayberg et al., 1984; Cowen et al., 1986, 1987; present report). We hypothesized that the trigeminal ganglion cells innervating the MCA may be competing with the superior cervical projection for target area or for a target factor for survival, and thus the removal of the superior cervical projection at birth (sympathectomy) may promote the survival of some of the trigeminal-artery innervating cells that normally would die. Multiple fluorescent retrograde tracing was employed to analyze the postnatal development of the trigeminal projection to the MCA in sympathectomized and sibling control rats. We found that the SCG projection to the MCA exhibits a period of postnatal cell death. The trigeminal ganglion projection exhibits axon degeneration as well as postnatal cell death. Postnatal day 0 (P0) lesioning of the SCG did not prevent cell death or axon loss in the trigeminal projection to the cerebral artery. In fact, increased cell death of the trigeminal-artery projecting neurons was observed in the lesioned animals when compared to nonlesioned sibling controls. By P55, we found that 80% of these trigeminal neurons had died in lesioned animals, compared with 50% in controls. In both control and sympathectomized rats, close to 90% of the trigeminal neurons innervating the artery in the neonate can no longer be retrogradely labeled from the MCA by tracer applications at P25–90. Thus, although the presence of an intact SCG may protect some trigeminal-artery projecting neurons from cell death, it does not prevent axon retraction and does not permit a larger absolute number of trigeminal axons to innervate the arteries in the adult. Thus, separate mechanisms are responsible for the survival of perikarya versus the retraction of their axons from the MCA. Surprisingly, in the neonatally sympathectomized rats almost 20% of those trigeminal cells that maintained a projection to the MCA at P90 also had a projection to the forehead. In contrast, less than 3% of the artery innervating trigeminal cells in the P90 control rats had an axon collateral to the forehead.(ABSTRACT TRUNCATED AT 400 WORDS)
Activation of GABAA receptors causes presynaptic and postsynaptic inhibition at synapses between muscle spindle afferents and motoneurons in the spinal cord of bullfrogs
Authors: Peng YY , Frank E
Published: March 2018

The functional role of GABAA receptors in inhibition of synaptic transmission between muscle spindle afferents and spinal motoneurons was studied in the isolated spinal cord of bullfrogs. Extracellular recording from the ventral root showed that activation of GABAA receptors by muscimol (primarily a GABAA receptor agonist) at 50 microM produced a 38% reduction in the amplitude of the excitatory postsynaptic potential (EPSP) evoked by stimulation of triceps muscle sensory afferents and a 66% reduction in the EPSP half-width, suggesting a large increase in the conductance of the motoneuronal membrane. Quantal analysis of unitary triceps EPSPs recorded intracellularly from motoneurons showed that muscimol reduced the quantal content of release (presynaptic inhibition). In addition, muscimol decreased the quantal size (postsynaptic inhibition) when the postsynaptic conductance change was large. Because the effects of muscimol were completely and reversibly blocked by 100 microM bicuculline (a specific GABAA receptor antagonist), both the pre- and the postsynaptic inhibition caused by muscimol were due to activation of GABAA receptors. Activation of GABAA receptors thus causes both pre- and postsynaptic inhibition of synaptic transmission between muscle afferents and spinal cord motoneurons in the frog.