bluuebunny/crossref_metadata_2025 huggingface dataset:
Receptive Fields of Neurons in the Owl's Auditory Brainstem Change Dynamically
Authors: Wagner Hermann
Published: April 2006

Binaural neurons in the barn owl's auditory brainstem have spatial receptive fields. It is shown here that both the frequency tuning of these neurons and their tuning to interaural time difference (ITD), the prime cue for azimuthal sound localization, improves with time after stimulus onset, a process I shall term ‘dynamic sharpening’. Thus, the receptive fields of these neurons also have a temporal dimension. Data were collected in four hierarchically ordered nuclei concerned with the computation of ITD: the nucleus ventralis lemnisci lateralis, pars anterior (VLVa), and three subnuclei in the inferior colliculus. Dynamic sharpening in the frequency tuning curves is evident from a dynamic reduction of tuning width. When stimulated with a tone, the response of all neurons varies in a cyclic manner with ITD. The ITDs at the response peaks differ by one period of the stimulus tone. The responses with noise stimulation are similar to the responses with tonal stimulation in all but the hierarchically highest nucleus, the external nucleus of the inferior colliculus. In this nucleus are found neurons that, if stimulated with noise, respond maximally only to one ITD while the responses at the other peaks are suppressed. This sidepeak suppression is a dynamic process. Dynamic sharpening of ITD tuning is also evident from a dynamic reduction of the tuning width around each of the response peaks. The proportion of neurons showing dynamic sharpening of ITD tuning is the same in all collicular subnuclei, but is lower in VLVa. Therefore, a major component of dynamic sharpening of ITD tuning occurs at the first station of the inferior colliculus. Lateral inhibition is one of the mechanisms underlying dynamic sharpening. Part of the inhibition may be mediated by GABA (Fujita and Konishi, 1988). The function of dynamic sharpening of ITD tuning may be to increase the fine representation of auditory space in single neurons.
Schwann Cells Secrete a PDGF‐like Factor: Evidence for an Autocrine Growth Mechanism involving PDGF
Authors: Eccleston P. A. , Collarini E. J. , Jessen K. R. , Mirsky R. , Richardson W. D.
Published: April 2006

We have investigated the influence of platelet‐derived growth factor (PDGF) in peripheral nervous system gliogenesis using two types of Schwann cell cultures. Short‐term Schwann cell cultures grow very slowly, but when maintained in culture for several months the division rate of some cells increases, and cell lines can be established. We show that Schwann cells in both short‐ and long‐term culture possess PDGF receptors and synthesize DNA in response to PDGF. Competitive binding experiments show that Schwann cells express mainly PDGF β‐receptors and respond better to PDGF‐BB than to PDGF‐AA. Conditioned media from short‐and long‐term Schwann cell cultures contain PDGF‐like mitogenic activity, and anti‐PDGF immunoglobin partially inhibits DNA synthesis in long‐term Schwann cell cultures. Antibody neutralization experiments and Northern blot analyses both indicate that the predominant PDGF isoform in these cultures is PDGF‐BB. PDGF‐like activity is also detected in extracts of rat sciatic nerve. Taken together, these results suggest that PDGF‐BB may stimulate Schwann cell proliferation in an autocrine manner during normal development.
Bicuculline‐ and Phaclofen‐Resistant Hyperpolarizations Evoked by Glutamate Applications to Stratum Lacunosum‐Moleculare in CA1 Pyramidal Cells of the Rat Hippocampus In Vitro
Authors: Williams Sylvain , Lacaille Jean‐Claude
Published: April 2006

In the hippocampus, different types of interneurons may mediate distinct gamma‐aminobutyric acid (GABA) responses, i.e. the early and late inhibitory postsynaptic potentials (IPSPs). To verify this hypothesis, intracellular recordings were obtained from CA1 pyramidal cells (n= 63) in rat hippocampal slices. Glutamate (1 mM) was locally ejected in stratum lacunosum‐moleculare to activate interneurons in this region. Glutamate‐evoked hyperpolarizing responses were characterized in pyramidal cells and compared to the early IPSP and the late IPSP elicited by stratum radiatum electrical stimulation. Several characteristics were similar for the glutamate‐evoked IPSPs and late IPSPs: their amplitude was small (−3.4 versus −4.9 mV, respectively), each was associated with a small conductance increase (5.0 versus 9.3 nS, respectively), their peak latency was slow (124.4 versus 129.8 ms, respectively) and in the majority of cells, each displayed little response reversal. However, the equilibrium potential of the glutamate IPSP (−76.5 mV) was similar to that of the early IPSP (−73.8 mV). Perfusion with a low Ca2+ (0.5 mM)/high Mg2+ (8 mM) medium or with tetrodotoxin (1 μM), which blocked synaptic transmission, also reduced the glutamate IPSP. Therefore the glutamate IPSP may be mediated indirectly by inhibitory interneurons. The GABAA antagonist bicuculline (10 μM), or picrotoxin (10–20 μM), blocked the early IPSP, but not the glutamate IPSP. The GABAB antagonist phaclofen (1 mM) attenuated the late IPSP, but did not affect the glutamate IPSP. The results of these experiments suggest that glutamate stimulation of interneurons in stratum lacunosum‐moleculare evokes a slow IPSP different from the GABA‐mediated early and late IPSPs in CA1 pyramidal cells of the hippocampus.
Comparison of Effects of Various Types of NA and 5‐HT Agonists on Transmission from Group II Muscle Afferents in the Cat
Authors: Bras H. , Jankowska E. , Noga B. , Skoog B.
Published: April 2006

A number of noradrenaline and serotonin agonists were tested to investigate which of them replicate the depressive actions of monoamines on transmission from group II muscle afferents in the cat spinal cord. The agonists were applied ionophoretically at the two sites at which maximal monosynaptic focal field potentials are evoked from group II afferents—in the intermediate zone and the dorsal horn of the 4th and 5th lumbar segments. Their effects were estimated from changes in the amplitude of the field potentials. The compounds tested fell into three categories according to the site at which they depressed transmission from group II afferents: one category with highly selective actions in the intermediate zone, a second category with similarly selective actions in the dorsal horn, and a third category with non‐selective actions. Drugs in the first category included three noradrenaline agonists (tizanidine, B‐HT 933 and clonidine), included in the second were five serotonin agonists (8‐OH‐DPAT, 5‐methoxytryptamine, α‐methyl serotonin, DOI and 2‐methyl‐serotonin), and in the third two noradrenaline agonists (phenylephrine and isoproterenol) and two serotonin agonists (RU 24969 and 5‐carboxamidotryptamine). Field potentials evoked by group I afferents remained unaffected by all but one compound (8‐OH‐DPAT). Effects of one noradrenaline agonist and one serotonin agonist (tizanidine and 5‐methoxytryptamine) were also tested on responses of single extracellularly recorded neurons. Tizanidine depressed responses induced by stimulation of group II afferents in intermediate zone interneurons, but not in dorsal horn neurons, while 5‐methoxytryptamine depressed activation of the latter. Tizanidine had no effect on responses evoked by group I afferents, either in intermediate zone interneurons or in the dorsal spino‐cerebellar tract neurons of Clarke's column. It is hypothesized that noradrenaline and serotonin released by descending monoaminergic neurons differ in the potency with which they depress transmission from group II afferents to different functional types of neuron. The results suggest that this depression may involve different membrane receptors at different locations, primarily α2 adrenoceptors in the intermediate zone/ventral horn and 5‐HT‐1A serotonin receptors in the dorsal horn.
Synaptic Connections of Different Strength Between Wind‐sensitive Hairs and an Identified Projection Interneuron in the Locust
Authors: Pflüger H.‐J. , Burrows M.
Published: April 2006

An identified intersegmental interneuron in Locusta and Schistocerca, with its cell body in the fourth abdominal ganglion and an axon which projects to the brain is excited by mechanosensory inputs from receptors on the head and neck. The organization of its receptive field, the types of sensory receptors which contribute to it and the patterns and strengths of the afferent connections were investigated by intracellular recording from the axon of the interneuron close to a spike‐initiating site in the prothoracic ganglion. The receptive field of the interneuron consists of a small patch of hairs on the head ipsilateral to the axon, and from hairs on two regions of the prosternum (a cuticular structure on the ventral surface of the prothoracic segment), first an ipsilateral, lateral region and second a medial but contralateral region. Hairs on the pronotum (dorsal neck) also contribute but were not investigated here. Each spike in the afferent from a hair with a filiform appearance and with a pigmented base on the prosternum consistently evokes an EPSP in the interneuron. These have a short and constant latency, indicating that the connection is probably direct. The head hairs also appear to make direct connections with the interneuron in the prothoracic ganglion, so that the spike‐initiating site here can integrate signals evoked by wind on the head and on the prosternum. Stiff tactile hairs on the prosternum do not connect with the interneuron. The EPSPs evoked by the long filiform hairs are consistently larger than those produced by the short filiform hairs and a single spike in some of the afferents from the long filiform hairs can evoke a spike in the interneuron. The effectiveness of an afferent is therefore correlated with the length of the filiform hair it innervates. The hairs with the most powerful effects are always the longest and occur in the same position on every locust. The shape of the receptive field and the different strengths of connections are apparent even in early larval instars. The axonal branches of the interneuron are restricted to the same side of the ganglion as the axon itself. Afferents from filiform hairs on the medial region of the prosternum project contralaterally, and those from the lateral region project ipsilaterally. Afferents from some of the head hairs project ipsilaterally directly to the prothoracic ganglion. The terminals of all these afferents overlap with the branches of the interneuron. By contrast, the afferents of tactile hairs which do not connect, project to different regions of neuropile. The connections ensure that the high sensitivity of the filiform hairs is maintained at the first stage in the central processing and suggest a role for this interneuron in supplying information about small changes in air currents that may be of use in controlling steering manoeuvres during flight.
Characterization and Function of Spinal Excitatory Interneurons with Commissural Projections in Xenopus laevis embryos
Authors: Roberts Alan , Sillar Keith T.
Published: April 2006

The multipolar somata of dorsolateral commissural (dlc) interneurons (Roberts and Clarke, 1982) lie in a superficial dorsolateral position in the spinal cord of Xenopus laevis embryos. By applying horseradish peroxidase to one‐half of the 100 μm diameter spinal cord, these neurons have been backfilled. Their dendritic branching pattern, commissural axonal projection and distribution near the time of hatching is described. Using Lucifer yellow‐filled microelectrodes a population of sensory interneurons with dlc morphology has been identified. They have multipolar somata in a dorsolateral superficial position, obliquely projecting dendrites and a ventral commissural axon. They receive presumed monosynaptic excitation in response to electrical stimulation of sensory neurites in the skin on the same side as the soma. During fictive swimming activity in curarized embryos the die interneurons are rhythmically inhibited in time with ventral root discharge on the same side. Die interneurons can fire multiple impulses and can turn on fictive swimming when stimulated by intracellular current injection. Skin stimulation is followed by excitatory postsynaptic potentials (EPSPs) in contralateral ventral rhythmic neurons. These EPSPs are reduced by the application of NMDA receptor antagonist. We conclude that dlc interneurons are excited by primary skin afferent Rohon ‐ Beard neurons, carry sensory information across the spinal cord to excite neurons on the opposite side by release of an excitatory amino acid transmitter and participate in reflexes and in the initiation of swimming.
Spontaneous Saccades and Gaze‐Holding Ability in the Pigmented Rat. I. Effects of Inferior Olive Lesion
Authors: Strata P. , Chelazzi L. , Ghirardi M. , Rossi F. , Tempia F.
Published: April 2006

We have studied the effects of lesion of the inferior olive on the spontaneous eye movements performed both in the light and dark in head restrained pigmented rats. The inferior olive lesion was made at least 1 month before study with 3‐acetylpyridine and eye movements were recorded through a phase detection search coil apparatus. Following lesion, the spontaneous saccades performed in the dark present a postsaccadic drift which is made up of two components characterized by their different time courses, the first one being fast and the second one slow. The latter component is due to the leakage of the neural integrator and the former is mainly the consequence of a mismatch between the phasic and the tonic component of the ocular movement. In the light only the first component is present and then the eye maintains a steady position. After the lesion the saccades in the dark present a time constant of the slow component of the postsaccadic drift which is significantly reduced to −600–900 ms from a value of 1600–4000 ms of the intact rats. This means that the integrity of the inferior olive is necessary to keep the time constant of the neural integrator within the physiological range. In the light, the amplitude of the postsaccadic drift depends on two factors. First, there is a mismatch between the phasic and the tonic components of the ocular movement, which are due to the pulse and the step of innervation of the extraocular muscles respectively. Different types of analysis have shown that the gain of the pulse to step transformation is about 0.77 at all saccadic amplitudes and eccentricities. Second, there is an increased leakiness of the neural integrator. Such a contribution increases linearly as a function of the eccentricity with a slope of 0.21. The main sequence of the saccades is not appreciably affected by the olivary lesion. Thus, the consequence of the inferior olive lesion may be interpreted as a general disruption of the integration process which, in physiological conditions, generates a proper and sustained oculomotor signal. More generally, it may be viewed as a loss of coordination between phasic and tonic motor commands.
Neurotensin‐like Peptides in the CNS of Lampreys: Chromatographic Characterization and Immunohistochemical Localization with Reference to Aminergic Markers
Authors: Brodin Lennart , Theordorsson Elvar , Christenson Johan , Cullheim Staffan , Hökfelt Tomas , Brown John C. , Buchan Alison , Panula Pertti , Verhofstad Albert A. J. , Goldstein Menek
Published: April 2006

Neurotensin (NT)‐like peptides in the CNS of the lamprey Lampetra fluviatilis were studied by radioimmunoassay (C‐terminal specific NT antiserum), reverse‐phase HPLC and immunohistochemistry. Multiple peaks of NT‐immunoreactive (‐ir) material were observed upon HPLC, of which a major peak eluted in the position of bovine NT. Immunofluorescence histochemistry showed that a monoclonal antibody recognizing the N‐terminal (1–11) fragment of NT, as well as two polyclonal NT antisera labelled a large number of cell bodies in the periventricular area of hypothalamus, including the postinfundibular commissural nucleus and the ventral and dorsal hypothalamic nuclei. Additional groups of NT‐ir cells were observed in the preoptic nucleus, the postoptic commissural nucleus, the mesencephalic tegmentum (L.fluviatilis), and in the spinal cord (L.fluviatilis and Ichtyomyzon unicuspis). Dense NT‐ir fibre plexuses were present in the caudal hypothalamus, corpus striatum, ventral mesencephalon, and in the dorsal horn and lateral margin of the spinal cord. At the ultrastructural level the lateral spinal margin showed NT‐ir terminal structures, which in most cases were not associated with synaptic specializations, although occasional synaptic contacts with unlabelled elements were found. The relation between NT‐ir and monoamine‐containing cells was examined with immunofluorescence double‐staining, using antisera to tyrosine hydroxylase (TH), 5‐hydroxytryptamine (5‐HT), and histamine respectively. In the periventricular nuclei of hypothalamus numerous TH‐, 5‐HT‐, as well as histamine‐ir cells were located in close association with NT‐ir cells, but none of the aminergic markers could be detected within NT‐ir neurons. The chemical properties as well as the anatomical distribution of lamprey NT‐like peptides show several similarities with those present in mammals, suggesting that NT‐containing neuronal systems in the CNS developed early in vertebrate phylogeny.
Mutual Re‐excitation with Post‐Inhibitory Rebound: A Simulation Study on the Mechanisms for Locomotor Rhythm Generation in the Spinal Cord of Xenopus Embryos
Authors: Roberts Alan , Tunstall M. J.
Published: April 2006

We have used computer simulations as one way to test the hypothesis that locomotor rhythm production for swimming in frog embryo spinal cord depends on rebound from inhibition and is sustained by mutual re‐excitation among spinal excitatory interneurons. All simulations were based on physiological and anatomical data on the neurons and circuitry of Xenopus embryo spinal cord.

Model ‘neurons’ had resistively coupled axon, soma, and dendrite compartments. Membrane properties were based on Hodgkin‐Huxley equations with resting potential at −75 mV and where soma and dendrite had reduced K+ and Na+ conductance and slowed K+ conductance. These ‘neurons’ fired a single non‐overshooting spike both to depolarizing current and afer hyperpolarizing current given during imposed depolarization. Synapses were made on to the dendrite. Inhibitory and excitatory synaptic channels had Nernst potentials of ‐80 and 0 mV, time constants for opening of 1 ms, and closing of 6 and 75 ms. When the short inhibitory postsynaptic potential occurred on the long (N‐methyl‐D‐aspartate‐type) excitatory postsynaptic potential, it led to rebound firing.

A four ‘neuron’ symmetrical network was built with reciprocal inhibition and where excitatory ‘neurons’ re‐excited themselves and the inhibitory ‘neuron’ on their own side. The rhythmic alternating activity with one spike per cycle produced reliably by this network was self‐sustaining, initiated by a brief synaptic input, and closely resembled the spinal cord motor pattern during swimming. The robustness of this activity pattern was investigated by varying cellular and synaptic parameters, initiating inputs, and network connectivity. We conclude that cellular, synaptic, and network properties are all important and that mutual re‐excitation, a form of positive feedback, could sustain motor rhythm production in the Xenopus embryo spinal cord.
Galanin and Glibenclamide Modulate the Anoxic Release of Glutamate in Rat CA3 Hippocampal Neurons
Authors: Ben‐Ari Y.
Published: April 2006

The effects of brief anoxic episodes on intracellularly recorded CA3 pyramidal neurons have been studied in the hippocampal slice preparation. Anoxia induced a depolarization occasionally preceded by a transient hyperpolarization associated with a fall in input resistance. The anoxic depolarization was due to the release of glutamate from presynaptic terminals since it was blocked by tetrodotoxin (TTX) (1 μM) or by the broad spectrum excitatory amino acid antagonist kynurenate (1 mM). In the presence of TTX (1 μM) or kynurenate (1 mM), anoxia only induced a hyperpolarization which was due to activation of a K+ conductance. The anoxic depolarization was blocked by galanin, a hormone which activates ATP sensitive K+ (K + ATP) channels. Anoxic depolarization was increased by the potent sulfonylurea agent glibenclamide (GLIB) which blocks K + ATP channels. Bath applications of these agents had little effect when applied in oxygenated Krebs solution suggesting that their action may be mediated by K + ATP channels. Since excessive release of glutamate during anoxia is neurotoxic, agents such as galanin which activate K + ATP channels may provide tissue specific protection against anoxic damage.
Regulation of Nerve Growth Factor (NGF) Synthesis in the Rat Central Nervous System: Comparison between the Effects of Interleukin‐1 and Various Growth Factors in Astrocyte Cultures and in vivo
Authors: Spranger Matthias , Lindholm Dan , Bandtlow Christine , Heumann Rolf , Gnahn Hannes , Näher‐Noé Martina , Thoenen Hans
Published: April 2006

In order to obtain information on the physiological regulation of NGF‐synthesis in the central nervous system (CNS) we investigated the effects of a series of growth factors (known to be present in the CNS) in cultures of purified rat astrocytes and compared these effects with those observed after intraventricular injection of the same molecules. After preliminary experiments had shown that 10% fetal calf serum (FCS) produced a marked increase in NGF‐mRNA levels in astrocytes (but neither in microglia nor oligodendrocytes) as demonstrated by Northern blot analysis and in situ hybridization the experiments were performed at low (0.5%) FCS concentrations. Supramaximal concentrations of IL‐1 and various growth factors caused a 5‐ to 7‐fold increase in NGF‐mRNA after 6 h. By 24 h the NGF‐mRNA levels approached control values again, most probably due to inactivation of the added factors since after readdition after 24 h the response was about the same as the initial one. Norepinephrine and 8‐bromo‐cAMP did not change NGF‐mRNA levels. The growth factor‐mediated changes in NGF‐mRNA levels in astrocyte cultures were not consistently reflected by the changes observed after intraventricular injection. IL‐1 produced by far the largest increase in hippocampal NGF‐mRNA after intraventricular injection. This large response to IL‐1 could result from a positive feedback mechanism, since IL‐1β injection not only increases NGF‐mRNA but also IL‐1β‐mRNA in the hippocampus. The understanding of the physiological regulation of NGF synthesis in the CNS is the basis for a rational approach to its pharmacological modification. This, in turn, is an attractive alternative to the (long‐term) infusion of NGF or the transplantation of NGF‐secreting cells with the goal of providing trophic support to the cholinergic neurons of the basal forebrain nuclei. These neurons are consistently affected in the early stages of Alzheimer's disease, their impaired function being essentially responsible for the cognitive deficits.
Behavioural Effect of Engineered Cells that Synthesize L‐DOPA or Dopamine after Grafting into the Rat Neostriatum
Authors: Horellou Philippe , Marlier Lionel , Privat Alain , Mallet Jacques
Published: April 2006

Cell lines in which tyrosine hydroxylase was introduced either by infection or transfection were used in grafting experiments in a rat model of Parkinson's disease obtained by unilateral lesion of the substantia nigra. A neuroblastoma NS20 Y cell line which synthesizes only L‐DOPA and a neuroendocrine AtT‐20 cell line which produces dopamine were obtained. They were grafted into denervated striata and their ability to compensate for the dopaminergic deficit was studied. Both modified cell types displayed a rapid partial reversal of apomorphine‐induced turning behaviour. No effect was observed with the control unmodified cell lines. We discuss the usefulness of engineered cell lines to address the fundamental issues in grafting experiments and more particularly in the therapy of Parkinson's disease.
Steroid Modulation of Muscarinic Cholinergic and α2‐Adrenergic Receptor Density in the Nucleus Intercollicularis of the Japanese Quail
Authors: Ball Gregory F. , Balthazart Jacques
Published: April 2006

Androgen modulation of neurotransmitter receptor density was investigated in the nucleus intercollicularis (ICo) of male and female Japanese quail (Coturnix coturnix japonica). ICo appears to play an important role in the neural control of testosterone (T) dependent vocal behaviour. Two receptor types were investigated in this nucleus; muscarinic cholinergic receptors, labelled using [3H]N‐methyl scopolamine (NMS) as the ligand, and α2‐adrenergic receptors, labelled using [3H]p‐amino‐clonidine (PAC) as the ligand. Changes in receptor density were assessed using in vitro quantitative autoradiography to ensure a high degree of anatomical specificity in the identification of any steroid effects. Gonadectomy was found to reduce the density of both [3H]PAC bindings sites and [3H]NMS in specific subregions of ICo. Gonadectomized animals treated with T had levels of receptor density similar to intact birds. However, the location within ICo of the effects of T was different for each ligand. [3H]NMS binding was modulated only in a rostral subregion of the nucleus while changes in [3H]PAC receptor density were found in the medial and lateral parts of ICo at a more caudal level. These changes in receptor density parallel changes in crowing frequency that are known to occur in males and females following castration and T treatment. The receptor systems may constitute a part of the neurochemical mechanism regulating vocal behaviour.
Glutamine Synthetase is Expressed by Primary Sensory Neurons from Chick Embryos In Vitro but not In Vivo: Influence of Skeletal Muscle Extract
Authors: Barakat‐Walter I. , Droz B.
Published: April 2006

Glutamine synthetase (GS) catalyses the ATP‐dependent formation of glutamine from glutamate and ammonia. To determine whether dorsal root ganglion (DRG) cells from chick embryos express the enzyme in vivo or in vitro, GS was detected by immunocytochemical reaction either in vibratome sections of DRG or in dissociated DRG cell cultures. The immunocytochemical detection of GS showed that in vivo the DRG taken from chick embryos at day 10 (E10), E14, E18 or from chickens after hatching were free of any GS‐positive ganglion cells; in contrast, in neuron‐enriched cultures of DRG cells grown in vitro at E10, virtually all the neuronal cells (98.6±1.0%) express GS at 3, 5 or 7 days of culture. In mixed DRG cell cultures, only 83.6±4.6% of the neurons displayed a GS‐immunoreactivity. In both culture conditions, neither the presence of horse serum nor the age of the culture appeared to affect the percentage of neurons which displayed a GS‐immunoreactivity. After [3H]glutamine uptake, radioautographs revealed that only 80% of the neurons were labelled in neuron‐enriched DRG cell cultures while 96% of the neurons were radioactive in mixed DRG cell cultures. Furthermore the most heavily [3H]glutamine‐labelled neurons were exclusively found in mixed DRG cell cultures. Combination of both immunocytochemical detection of GS and radioautography after [3H]glutamine uptake showed that strongly GS‐immunostained neurons corresponded to poorly radioactive ones and vice versa. When skeletal muscle extract (ME) was added to DRG cell cultures, the number of GS‐positive neurons was reduced to 77.5±2.5% in neuron‐enriched cultures or to 43.6±3.8% in mixed DRG cell cultures; in both types of culture, the intensity of the neuronal immunostaining was depressed. Furthermore, combined action of ME and non‐neuronal cells potentiates the enzyme repression exerted separately by ME or non‐neuronal cells. Since GS‐immunoreactivity is expressed in DRG cells grown in vitro, but not in vivo, it is suggested that microenvironmental factors influence the expression of GS. More specifically, the repression of GS by primary sensory neurons grown in vitro may be strongly induced by soluble factors present in skeletal muscle, and to a lesser extent in brain, and potentiated by non‐neuronal cells.
The Importance of Graft Placement and Task Complexity for Transplant‐Induced Recovery of Simple and Complex Sensorimotor Deficits in Dopamine Denervated Rats
Authors: Mandel Ronald J. , Brundin Patrik , Björklund Anders
Published: April 2006

The present study examined the role of graft placement and behavioural task complexity in determining the functional efficacy of intrastriatal grafts of dopamine‐rich fetal ventral mesencephalon (VM) placed in the dopamine (DA) depleted striatum. The functional effects of two different striatal placements of VM grafts were evaluated using tests of drug‐induced motor asymmetry, simple sensorimolor orienting response, and a more complex sensorimotor integrative task (disengage behaviour), in which the rat has to perform the orienting response while in the act of eating. Rats with complete unilateral 6‐hydroxydopamine (6‐OHDA) lesions of the mesostriatal DA pathway, received either implants of dissociated fetal VM in the central or ventrolateral portions of the denervated striatum. Nongrafted lesioned rats served as controls. Nine weeks after grafting, the rats were tested on separate days for disengage behaviour, sensorimotor orientation, and amphetamine‐induced rotational behaviour. Consistent with previous findings, the two graft placements had differential effects on drug‐induced motor asymmetry and sensorimotor responses: the centrally placed VM grafts reversed amphetamine‐induced rotational asymmetry but had little effect on the sensorimotor deficit, whereas the ventrolaterally placed grafts reversed the sensorimotor orientation deficits without any effect on the drug‐induced rotation. In contrast, fetal VM grafts, regardless of their placement, did not ameliorate the observed deficits in disengage behaviour; that is the grafted rats that had recovered their sensorimotor response in the absence of food were unable to perform the same orienting response while eating. These results provide evidence that functional intrastriatal VM grafts which are capable of restoring sensorimotor responses or motor asymmetry fail to affect lesion‐induced deficits in a task that requires more complex sensorimotor integration. It is suggested that the degree of anatomical integration of the grafted DA neurons into the host circuitry will determine the efficacy of the grafts to influence more complex sensorimotor integrative deficits in the DA lesion model.
Gamma‐Aminobutyric Acid‐Inhibitory Motor Innervation of Leg Muscles of the Shore Crab
Authors: Bévengut Michelle , Cournil Isabelle
Published: April 2006

The inhibitory motor innervation of a crustacean leg was studied in the crab, Carcinus maenas. In in vitro preparations of the central nervous system and the proximal leg nerves, motor nerve recordings demonstrate the presence of a single common inhibitory motor neuron which elicits picrotoxin‐sensitive inhibitory junction potentials in a distal leg muscle, the accessory flexor. This inhibitor is the common inhibitor (CI). Immunohistochemical detection of the inhibitory motor neuron neurotransmitter, gamma‐aminobutyric acid (GABA), allows us to identify three immunoreactive motor neuron axons in sections of the distal leg nerves and of proximal leg nerves. One corresponds to the CI whereas the other two are the specific inhibitors, one to the stretcher and one to the opener muscles. After nickel chloride backfills of the CI in proximal leg nerves, GABA immunodetection fails and thus confirms that CI is the single inhibitor having branches in proximal leg nerves.

These results demonstrate that the inhibitory motor innervation of a crab leg comprises three and only three inhibitors: the common inhibitor innervating all leg muscles and the two specific inhibitors, each innervating a single distal leg muscle. Further conclusions can be drawn: first, a muscle innervated by more than one excitatory axon has no specific inhibitor; second, sensory afferents are not mediated by GABA. Finally, during locomotion, the leg muscles receive two very distinct types of motor input: (1) one common to all the muscles coming from the common inhibitor which was previously shown by other authors to prevent build‐up of tension in the muscles, thus allowing each muscle to contract according to (2) the specific motor input it receives from its own excitors.
Two Monoclonal Antibodies Recognizing Carbohydrate Epitopes on Neural Adhesion Molecules Interfere with Cell Interactions
Authors: Fahrig Thomas , Schmitz Brigitte , Weber Dieter , Kücherer‐Ehret Andrea , Faissner Andreas , Schachner Melitta
Published: April 2006

We have studied two monoclonal antibodies raised against crude fractions of membrane glycoproteins from adult mouse brain and found them to react with two carbohydrate epitopes expressed on several neural cell adhesion molecules. Other identified and unidentified glycoproteins from different cell types, organs and species were also recognized by these antibodies. Both epitopes are N‐glycosidically linked mannosidic or hybrid type oligosaccharides and co‐expressed on all the glycoproteins so far tested. In spite of their remarkable similarities, the glycan epitopes are different as shown by ELISA competition assays. In microexplant outgrowth and cell adhesion assays, both antibodies interfere with neural cell adhesion, migration, and neurite outgrowth. These observations, together with previous studies on the L2/HNK‐1 glycan (Künemund et al., 1988), indicate that adhesion molecules carry various carbohydrate epitopes mediating different cell interactions in in vitro assays.
Spontaneous Activity as a Determinant of Axonal Connections
Authors: Cook Jeremy E. , Becker David L.
Published: April 2006

To investigate the role of spontaneous retinal activity in map refinement, we studied goldfish kept in darkness during regeneration of a cut optic nerve. In one experiment, such fish (with lenses ablated to blur vision) were maintained for 70 days in stroboscopic light, diurnal light, or total darkness interrupted daily by 15 minutes of stroboscopic light. The retinotectal projection was then assessed for retinotopy by standard methods, using retrograde transport of wheat germ agglutinin—horseradish peroxidase. As in previous work, significantly more refinement was found in diurnal than in stroboscopic light. In darkness, refinement was as complete as in diurnal light. In a second experiment, similar fish were kept in stroboscopic light for 63 days. Some were then assessed to confirm that refinement had been delayed, while others were transferred to darkness or diurnal light for assessment later. After 7 days in either environment, no further refinement was seen; but after 21 days, substantial and significant refinement has occurred in both. Thus the effects of darkness and diurnal light were indistinguishable, and very different from those of stroboscopic light and (in previous studies) tetrodotoxin. Map refinement is evidently activity‐dependent but not experience‐dependent, and can effectively use the correlated spontaneous firing of neighbouring ganglion cells as its basis. Locally correlated spontaneous activity, which appears also to drive eye‐ and class‐specific axon segregation in mammals, occurs widely in the nervous system. It could potentially generate systematic interconnection patterns even between neuronal populations without an overtly topographic organization.
Cortical Regulation of Striatal Neuropeptide Y (NPY)‐Containing Neurons in the Rat
Authors: Kerkerian L. , Salin P. , Nieoullon A.
Published: April 2006

This study examined the functional relationships established by nigral, cortical, and thalamic striatal afferent pathways with neuropeptide Y (NPY)‐containing neurons in the rat rostral striatum by coupling selective deafferentation procedures and NPY immunohistochemistry. Previous experiments have shown that after unilateral 6‐hydroxydopamine (6‐OHDA)‐induced degeneration of nigrostriatal dopaminergic neurons, the mean number of NPY‐immunoreactive (lr) neurons per frontal section was increased in the striatum ipsilateral to the lesion side and unaltered in the contralateral striatum. The present topographical analysis of the 6‐OHDA lesion effects led us to state that the increase in NPY‐lr neuron density occurs in restricted ventral and medial zones of the ipsilateral striatum. Unilateral ablation of the frontoparietal cerebral cortex by thermocoagulation was moreover shown to elicit, 20–30 days later, a significant bilateral increase in the number of striatal NPY‐lr cells. The increase was more marked in the striatum ipsilateral to the hemidecortication where it was similar in amplitude to that induced by the 6‐OHDA lesion. The topographical analysis of the cortical lesion effects also revealed an uneven striatal response, but, in contrast to that observed for the 6‐OHDA lesion, changes were restricted to dorsolateral areas of the striatum in both brain sides, revealing an apparent complementarity of nigral dopaminergic and cortical influences over striatal NPY neuronal system. Combined unilateral nigral and cortical lesions surprisingly counteracted in a survival time dependent manner the effects of each lesion considered separately. In that condition topographical changes related to the 6‐OHDA lesion totally disappeared and those related to the cortical lesion were attenuated but still present. These results suggest that expression of striatal dopamine—NPY interaction is dependent on corticostriatal transmission. Interestingly lesion of thalamic areas projecting to the striatum did not significantly modify the mean number of NPY‐lr neurons determined per section from the whole striatal surface, but selectively increased the NPY neuron density in the mediodorsal region of the striatum, suggesting that the striatal NPY‐containing neuronal system is also influenced by thalamostriatal projections.
Molecular Identification of the 62 kd Form of Glutamic Acid Decarboxylase from the Mouse
Authors: Katarova Z. , Szabo G. , Mugnaini E. , Greenspan R. J.
Published: April 2006

A series of overlapping clones coding for L‐glutamic acid decarboxylase was purified from a mouse brain cDNA library, the longest of which contains a 1869 bp open reading frame and 913 bp of non‐coding sequence. By comparison with the corresponding sequences from the mouse genome, it was determined that the first methionine in the longest cDNA represents the initiation codon. Expression of this cDNA in eukaryotic cells produces a 62 kd protein that is recognized by antiserum against rat GAD and which displays GAD activity commensurate with the amount of protein produced. Antibodies raised against the purified product of this cDNA recognize a 62 kd protein from mouse brain on immunoblots, specifically stain GABA‐ergic neurons in brain sections, and are capable of immunoprecipitating most GAD activity from mouse brain extracts. These results provide the first definitive identification of a cDNA coding for the larger of two forms of GAD in mouse brain, and suggest that the two forms are closely related.
Auditory Neurons with Transitory Axons to Visual Areas Form Short Permanent Projections
Authors: Clarke Stephanie , Innocenti Giorgio M.
Published: April 2006

The kitten's auditory cortex (including the first and second auditory fields Al and All) is known to send transient axons to either ipsi‐ or contralateral visual areas 17 and 18. By the end of the first postnatal month the transitory axons, but not their neurons of origin, are eliminated. Here we investigated where these neurons project after the elimination of the transitory axon. Eighteen kittens received early (postnatal day (pd) 2–5) injections of long lasting retrograde fluorescent traces in visual areas 17 and 18 and late (pd 35–64) injections of other retrograde fluorescent tracers in either hemisphere, mostly in areas known to receive projections from Al and All in the adult cat. The middle ectosylvian gyrus was analysed for double‐labelled neurons in the region corresponding approximately to Al and All. Late injections in the contralateral (to the analysed Al, All) hemisphere including all of the known auditory areas, as well as some visual and ‘association’ areas, did not relabel neurons which had had transient projections to either ipsi‐ or contralateral visual areas 17–18. Thus, Al and All neurons after eliminating their transient juvenile projections to visual areas 17 and 18 do not project to the other hemisphere. In contrast, relabelling was obtained with late injections in several locations in the ipsilateral hemisphere; it was expressed as per cent of the population labelled by the early injections. Few neurons (0–2.5%) were relabelled by large injections in the caudal part of the posterior ectosylvian gyrus and the adjacent posterior suprasylvian sulcus (areas DP, P, VP). Multiple injections in the middle ectosylvian gyrus relabelled a considerably larger percentage of neurons (13%). Single small injections in the middle ectosylvian gyrus (areas Al, All), the caudal part of the anterior ectosylvian gyrus and the rostral part of the posterior ectosylvian gyrus relabelled 3.1–7.0% of neurons. These neurons were generally near (< 2.0 mm) the outer border of the late injection sites. Neurons with transient projections to ipsi‐ or contralateral visual areas 17 and 18 were relabelled in similar proportions by late injections at any given location. Thus, Al or All neurons which send a transitory axon to ipsi‐ or contralateral visual areas 17 and 18 are most likely to form short permanent cortical connections. In that respect, they are similar to medial area 17 neurons that form transitory callosal axons and short permanent axons to ipsilateral visual areas 17 and 18.
Transient Sensitivity of Rat Cerebellar Purkinje Cells to N‐methyl‐D‐aspartate during Development. A Voltage Clamp Study in in vitro Slices
Authors: Krupa M. , Crepel F.
Published: April 2006

In vitro sagittal slices of immature rat cerebellum were used to study the development of the sensitivity of Purkinje cells (PC) to L‐glutamate (Glu) and N‐methyl‐D‐aspartate (NMDA). In 8‐day‐old animals, all PCs recorded in magnesium‐free medium responded to iontophoretic applications of both agonists by transient and dose dependent inward currents which, in both cases, were heavily contaminated by a Glu and NMDA‐induced synaptic noise. When 5 × 10−6 M tetrodotoxin (TTX) was added to the perfusing medium, this evoked synaptic noise was completely abolished in most cells whereas clear‐cut inward currents induced in PCs by Glu and NMDA applications on their dendrites were still visible. These responses were selectively antagonized by the non‐NMDA glutamate receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and by the NMDA receptor antagonist D‐2‐aminophosphono‐5‐valeric acid (2APV) respectively. Excitatory responses induced by aspartate in 8– 10‐day‐old PCs were also markedly antagonized by CNQX. At this stage, the sensitivity of PCs to NMDA was about one order of magnitude less than that to Glu. In 15–20‐day‐old animals, all PCs were still responsive to Glu whereas only 70% of them were still excited by NMDA in the presence of TTX in the bath. Furthermore, the sensitivity of PCs to Glu was higher than at 8 days of age, whereas that to NMDA was significantly lower, even when considering only those cells which still responded to this agonist. This trend was still accentuated later on since at 2 months of age, only 25% of PCs were excited by NMDA whereas their sensitivity to Glu was similar to that observed in 15–20‐day‐old animals. Therefore, the present results are fully consistent with the view that PCs have a transient expression of NMDA receptors during development.
Time‐related Changes in Basal Phosphoinositide Turnover after Induction of Long‐term Potentiation in the Dentate Gyrus are Blocked by Commissural Stimulation
Authors: Clements M. P. , Errington M. L. , Bliss T. V. P. , Lynch M. A.
Published: April 2006

We have examined basal phosphoinositide turnover in synaptosomes obtained from the dentate gyrus of anaesthetized rats in which long‐term potentiation was induced unilaterally in perforant path‐granule cell synapses. Relative to the unpotentiated side. [3H]myo‐inositol labelling of inositol phosphates was significantly enhanced 45 min and 3 h after induction of long‐term potentiation, but reduced after 2.5 min. Similarly, [14C]arachidonic acid labelling of 1,2‐diacylglycerol was increased 45 min and 3 h after induction of long‐term potentiation, but reduced after 2.5 min. In a second series of experiments, induction of long‐term potentiation was blocked by stimulation of the commissural projection to granule cells. In synaptosomes prepared from this tissue, there was no difference in phosphoinositide turnover between tetanized and control sides at any of the three post‐tetanic intervals. We conclude that in the dentate gyrus, long‐term potentiation is associated with an increase in phosphoinositide turnover which is established between 2.5 min and 45 min post‐tetanus and which persists for at least 3 h.
Nerve Growth Factor Regulates Expression of the Nerve Growth Factor Receptor Gene in Adult Sensory Neurons
Authors: Lindsay R. M. , Shooter E. M. , Radeke M. J. , Misko T. P. , Dechant G. , Thoenen H. , Lindholm D.
Published: April 2006

Sensory neurons of the adult rat dorsal root ganglion (DRG) can be maintained in culture in the absence of nerve growth factor (NGF). We have thus used dissociated cultures of these neurons to study effects of NGF on the regulation of expression of mRNA encoding the nerve growth factor receptor (NGF‐R). In the absence of NGF, levels of NGF‐R mRNA remained constant for 7 days in cultures of adult rat DRG neurons. In the presence of NGF, NGF‐R mRNA levels rose two ‐ three‐fold after 2 days, reaching plateau levels (five ‐ six‐fold elevation) after 5 days. This NGF‐induced up‐regulation could be demonstrated even after prior NGF‐deprivation for 3–4 days. NGF had no effect upon NGF‐R mRNA levels in DRG non‐neuronal cells. Epidermal growth factor (EGF), fibroblast growth factor (FGF) and ciliary neurotrophic factor (CNTF) were without effect on NGF‐R mRNA levels, but 8‐bromo‐cAMP decreased NGF‐R mRNA levels by 65% after 2 days. NGF also induced a rapid (30 min) rise in expression of c‐fos in DRG neurons, but not in non‐neuronal cells. Our results suggest that endogenous levels of NGF may regulate the expression of NGF‐R in vivo.
Evidence that the Rate of Wallerian Degeneration is Controlled by a Single Autosomal Dominant Gene
Authors: Perry V. H. , Lunn E. R. , Brown M. C. , Cahusac S. , Gordon S.
Published: April 2006

In a substrain of C57BL mice, C57BL/Ola, Wallerian degeneration in the distal segment of the severed sciatic nerve is extremely slow when compared to other mice. Despite this very slow degeneration in the distal segment regeneration of the motor nerves is not impaired. From suitable genetic outcrosses and backcrosses, the authors provide evidence that the rate of Wallerian degeneration in this strain is controlled by a single autosomal gene product. The authors have also shown that the rate of degeneration, in C57BL/Ola mice, is influenced by the environment in which the animals were bred and housed. Wallerian degeneration in the sciatic nerves of mice raised in isolators is slower than in those raised in a conventional animal house. This strain of mouse may prove to be of value in the understanding of nerve degeneration and regeneration.