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Biomedical subjects

B P Fulton

Publications and source records attributed to B P Fulton.

11 recordsLinked to original sources

Gap junctions in the developing nervous system.

Cell-cell interactions are important in the development of the nervous system. Gap junctions (GJs) form direct intercellular channels that permit diffusion of ions and small molecules and thus cells linked by GJs can influence each other's properties or behavior either through transmission of electrical signals or through transfer of signaling molecules. In the developing nervous system, widespread GJ communication occurs at the time of neural induction, but in the adult nervous system it is much more restricted. In addition, certain events in neural development appear to involve the formation of transient junctional connections. This review examines briefly four aspects of neural development in which GJs may be involved, namely, neurulation, regional differentiation, migration, and axon guidance.

Animals

Visualization of O-2A progenitor cells in developing and adult rat optic nerve by quisqualate-stimulated cobalt uptake.

Some macroglial cells of the O-2A lineage express glutamate receptor channels of the quisqualate/kainate type and take up extracellular cobalt when activated by glutamate agonists. These cells can be identified both in vitro and in situ following precipitation and intensification of the intracellular cobalt. We have used this technique to characterize these cells in the developing and adult rat optic nerve. In purified cultures of optic nerve cells, O-2A progenitor cells and type 2 astrocytes took up cobalt in the presence of quisqualate, while oligodendrocytes, type 1 astrocytes, and microglial cells did not. When whole optic nerves of various postnatal ages were exposed to quisqualate and cobalt, a subpopulation of glial cells took up cobalt. Cobalt uptake in vitro and in situ was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione. The number, morphology, and spatial distribution of cobalt-filled cells in situ varied with age. In perinatal nerves, 9% of glial cells took up cobalt. These cells had a simple unipolar or bipolar morphology and were two to three times more concentrated at the chiasm end than at the eye end of the nerve. During subsequent development, this gradient disappeared and the cobalt-filled cells became progressively more complex in morphology and increased in number and density, reaching a peak toward the end of the second postnatal week. The number subsequently declined to about 16,000 (7%) in the adult nerve. The processes of some cobalt-filled cells appeared to contact nodes of Ranvier. All cobalt-filled cells in 2 1/2-week-old optic nerves had a similar ultrastructural appearance and did not resemble either mature oligodendrocytes or astrocytes. Our results suggest that the cells stimulated by quisqualate to take up cobalt in the optic nerve are the in vivo counterpart of O-2A progenitor cells. We found no evidence that any of these cells are type 2 astrocytes.

Aging

Postnatal changes in conduction velocity and soma action potential parameters of rat dorsal root ganglion neurones.

The relationship between peripheral conduction velocity and the configuration of the soma action potential was examined in rat lumbar dorsal root ganglion neurones during the first two weeks of postnatal development. The results show that the soma membrane properties of A cells change as their conduction velocity increases during myelination, but that C cells retain the same soma membrane properties they express at birth, while their conduction velocity increases only slightly. It is suggested that the relationship between primary afferent axons and their associated Schwann cells may play a role in the differentiation of soma membrane properties of sensory neurones.

Action Potentials

Motoneurone activity in an isolated spinal cord preparation from the adult mouse.

This paper describes an isolated, hemisected preparation of adult mouse spinal cord, in which motoneurones remain viable. At 18-22 degrees C both orthodromic synaptic activation and antidromic invasion of populations of motoneurones could be demonstrated by extracellular recording of ventral root reflexes and ventral horn field potentials. Motoneurones had resting potentials of -55 to -65 mV and input resistances of 5-30 M omega, and, following ventral or dorsal root stimulation or during outward current injection, they generated action potentials which resembled those recorded from adult motoneurones in vivo. Recurrent inhibitory synaptic potentials followed antidromic spikes, demonstrating viability of the Renshaw cell pathway.

Animals

Ionic mechanisms underlying the firing properties of rat neonatal motoneurons studied in vitro.

Ionic mechanisms underlying the firing properties of spinal motoneurons of neonatal rats (postnatal days 3-10) have been investigated using a hemisected, in vitro spinal cord preparation. These results demonstrate the presence of a high-threshold voltage-dependent calcium response and partial sodium-dependent spikes. The calcium current is evident during the falling phase of the action potential and is the major component of the after-depolarizing potential. The subsequent increase in intracellular calcium concentration activates a calcium-dependent potassium conductance (gK-Ca), the major component of the after-hyperpolarizing potential. The gCa, by activating gK-Ca, is the primary determinant of firing rate in neonatal motoneurons. For, when gCa was blocked by Cd2+, the interspike interval decreased, the maximum firing rate and the slope of the firing frequency-injected current relation increased. The calcium current is particularly robust during the first few postnatal days; during this period, tetrodotoxin resistant action potentials can be elicited by direct stimulation under control conditions. In animals older than 5 days such calcium spikes could be elicited only after decreasing gK with intracellular Cs+ or extracellular tetraethylammonium. This was the case even when 1 mM of the bath CaCl2 was replaced with BaCl2. The rising phases of calcium spikes recorded from neurons in both age groups demonstrate several components suggesting the calcium spikes comprise several discrete events, which probably originate across the dendritic membrane. When gK was decreased by bath application of tetraethylammonium+ and Cs+, neonatal motoneurons generated prolonged Ca-dependent spikes lasting for up to 6 s. Repolarization of Ca spikes occurred in two stages, the first was rapid (-2.11 +/- 0.8 V/s, n = 6) but incomplete. The second, was slower (-0.01 +/- 0.003 V/s, n = 5) and returned the membrane potential to the resting level after about 1-2 s. It is suggested that accumulation of extracellular potassium may contribute to the slow phase of repolarization. Motoneurons from the younger age group (3-5 days old) demonstrate all-or-none partial spikes rising from the after-depolarization of directly elicited sodium-dependent action potentials. Similar partial spikes were elicited from neurons from older animals during intracellular Cs+ loading. The partial spikes had faster rates of rise than the tetrodotoxin-resistant spikes and were not seen after tetrodotoxin treatment, suggesting that they are sodium-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Electrophysiological properties of neonatal rat motoneurones studied in vitro.

The electroresponsive properties of neonatal lumbar spinal motoneurones were studied using isolated, hemisected spinal cords from neonatal rats aged 3-12 days. The extracellular and intracellular responses to electrical stimulation of the ventral and dorsal root were studied as well as the intracellular response to current injection. Field potentials recorded in the lateral motor area following electrical stimulation of lumbar ventral roots had a triphasic positive-negative-positive wave form. The negative component did not return to the base line smoothly but exhibited a 'shoulder' where the negativity increased in duration. Following electrical stimulation of the dorsal root, presynaptic field potentials were recorded upon activation of the afferent axons as well as following synaptic activation of interneurones and motoneurones. The input resistances of neonatal motoneurones determined from the slope of current-voltage plots were high compared with the adult. The resistance decreased with age with a mean of 18.1 M omega for animals 3-5 days old, 8.8 M omega for animals 6-8 days old and 5.4 M omega for animals 9-11 days old. Values for the membrane time constant were similar to those in the adult with a mean of 4.5 ms. Action potentials elicited by ventral or dorsal root stimulation or by intracellular current injection were marked by a pronounced after-depolarization (a.d.p.) and an after-hyperpolarization (a.h.p.). The amplitude of the a.h.p. varied with that of the a.d.p. The amplitude of excitatory post-synaptic potentials (e.p.s.p.s) elicited by electrical stimulation of the dorsal root was affected by intracellular current injection. Two types of e.p.s.p.s were distinguished: those with a biphasic reversal (early phase first) and those in which the early phase was unaffected by inward current injection while the later phase was reversed. Unlike in the adult, the reversals could be achieved with low current levels and the amplitude of both types of e.p.s.p. was increased by inward current injection. Inhibitory post-synaptic potentials (i.p.s.p.s) were elicited by dorsal or ventral root stimulation. The amplitude of these i.p.s.p.s was diminished and reversed in sign with inward current injection and their amplitude was enhanced with outward current injection. Activation of neonatal motoneurones with long current pulses revealed that there is one steady-state firing range.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Presynaptic acetylcholine receptors at the excitatory amino acid synapse in locust muscle.

Acetylcholine (greater than or equal to 10(-5) M) applied in the bathing medium to the excitatory nerve-muscle junction of the locust caused a dose-dependent increase in the frequency of spontaneous miniature potentials and in the mean quantal content of evoked potentials. The statistical characteristics of the spontaneous release process were also modified, high frequency bursts of spontaneous potentials and "giant' miniature potentials occurring in the presence of acetylcholine. The response, which was dependent on extracellular calcium concentration, consisted of two distinct phases; these could be induced or abolished selectively by nicotinic and muscarinic drugs, respectively. The results suggest the presence, in low density, of two types of cholinergic receptors on the excitatory motor nerve terminals of the locust. The acetylcholine-induced channels may admit calcium ions. The possible role of these presynaptic receptors is discussed.

Acetylcholine

Electrical synapses between motoneurons in the spinal cord of the newborn rat.

Ventral roots of the newborn rat spinal cord were stimulated while recording intracellularly from motoneurons. In many cells, stimulation subthreshold for an antidromic action potential in the impaled cell produced a small, short-latency depolarization, which was unaffected by membrane polarization. This response (antidromic synaptic potential, a.s.p.) was also seen, in some cells, on stimulating the ventral root of an adjacent segment. Replacement of Ca2+ (2 mM) with Mn2+ (3 mM) or Mg2+ (10 mM) completely abolished orthodromic synaptic potentials, but the a.s.p. persisted. These results strongly suggest that the a.s.p. is produced by an electrical interaction between motoneurons.

Animals

Effects of a Dendroaspis neurotoxin on synaptic transmission in the spinal cord and the neuromuscular junction of the frog.

A neurotoxin from the venom of Dendroaspis jamesoni was tested at the neuromuscular junction and at a cholinergic pathway in the isolated spinal cord of the frog. The toxin reduced the amplitude and time constant of decay of miniature endplate currents in the presence of prostigmine, indicating a curare-like action. In the spinal cord it selectively blocked transmission in the cholinergic pathway and increased spontaneous activity. Partial protection against toxin action in the spinal cord was provided by atropine or carbachol. The results suggest that the toxin acts on cholinergic receptors at both sites and also provide further evidence that the pharmacology of the two sites is different.

Animals