Blood vessels restrain pancreas branching, differentiation and growth.

How organ size and form are controlled during development is a major question in biology. Blood vessels have been shown to be essential for early development of the liver and pancreas, and are fundamental to normal and pathological tissue growth. Here, we report that, surprisingly, non-nutritional signals from blood vessels act to restrain pancreas growth.

An analysis of the long-lasting after-hyperpolarization of guinea-pig vagal motoneurones.

1. The long-lasting after-hyperpolarization which characterizes the neurones of the dorsal motor nucleus of the vagus in the guinea-pig was studied in vitro. 2.

Spatial and temporal analysis of calcium-dependent electrical activity in guinea pig Purkinje cell dendrites.

We have used the calcium indicator dye arsenazo III, together with a photodiode array, to record intracellular calcium changes simultaneously from all regions of individual guinea pig cerebellar Purkinje cells in slices. The optical signals, recorded with millisecond time resolution, are good indicators of calcium-dependent electrical events. For many cells the sensitivity of the recordings was high enough to detect signals from each array element without averaging.

Electrophysiology of degenerating neurones in the vagal motor nucleus of the guinea-pig following axotomy.

1. The electrophysiological properties of motoneurones in the dorsal motor nucleus of the vagus in the guinea-pig were studied at different times following cervical vagotomy. The results were compared both to normal neurones and to results obtained at the same time from intact neurones located in the contralateral nucleus.

Mapping calcium transients in the dendrites of Purkinje cells from the guinea-pig cerebellum in vitro.

1. A 10 X 10 photodiode array was used to detect stimulation-dependent absorbance changes simultaneously from many positions in the dendrite field of guinea-pig Purkinje cells which had been injected with the calcium indicator Arsenazo III in thin cerebellar slices. Signals from each element of the array were matched to positions on the cells by mapping them onto fluorescence photographs of Lucifer Yellow which had been co-injected into the cells with the Arsenazo III.

Time course and distribution of motoneuronal loss in the dorsal motor vagal nucleus of guinea pig after cervical vagotomy.

Cells in the dorsal motor vagal nucleus (DMVN) of the adult guinea pig were counted at different times after unilateral cervical section of the vagus nerve. The counts were made from serial 30 microns coronal sections throughout the DMVN in normal and operated animals. There are three types of cells in the DMVN of guinea pig: medium-sized motoneurons that are retrogradely filled by HRP from the site of the vagotomy, small neurons, and glial cells.

Sodium-dependent regenerative responses in dendrites of axotomized motoneurons in the cat.

Ten days after extradural axotomy, partial spikes are found in greater than 20% of cat L7 motoneurons, while 15-21 days after axotomy the incidence increases to 60%. These responses are produced in excitable (hot) spots in the dendrites by synaptic excitation. Intracellular injection of QX-314, a lidocaine derivative and effective blocker of Na+ channels from within neurons, results in elimination of partial spikes before blocking somadendritic spikes.

Intracellular injection of acetylcholine blocks various potassium conductances in vagal motoneurons.

Injection of acetylcholine into cholinergic neurons of the dorsal motor nucleus of the vagus induced membrane depolarization, an increase in input resistance, a decrease of early and late afterhyperpolarizations and a prolongation of the action potential. These effects were reversible and within 10-20 min almost complete recovery was always observed. Externally applied acetylcholine, even with doses as high as 15 mM, was not effective.

Depolarizing action of GABA (gamma-aminobutyric acid) on myelinated fibers of peripheral nerves.

The inhibitory neurotransmitter GABA (gamma-aminobutyric acid) has been shown to have a depolarizing action on myelinated axons of both mammalian and amphibian peripheral nerves. In initial in vivo observations intravenous injections of GABA caused an increase in the excitability of the low-threshold, fast conducting fibers of the superficial radial and median nerves of the cat. Similar, graded, reversible effects were confirmed (using changes in the amplitude/integral of the stimulus-evoked A-fiber submaximal compound action potential to assess excitability) in in vitro studies with the isolated, desheathed frog sciatic nerve.

Mediobasal hypothalamic neurons are excited by the iontophoretic application of sodium.

In the course of studies on the responsiveness of mediobasal hypothalamic neurons to the iontophoretic application of cortisol, it was found that positive currents applied to a sodium chloride (1 M) barrel alone, but not to a choline chloride (1 M) barrel, frequently increased the firing of these neurons. Subsequently, systematic examination demonstrated that out of 102 MBH neurons 52 (51%) increased their firing by at least 30% with application of NaCl, using currents no greater than 10 nA. No such effect was obtained in response to Na application from a dilute solution (0.

The effects of iontophoretic application of putative neurotransmitters on the electrical activity of rat mediobasal hypothalamic neurons in relation to their steroid sensitivity.

In order to characterize the neurons responsible for ACTH release and the suppression produced by adrenocortical steroids, we have studied the pharmacological sensitivity of neurons in the region containing the highest concentration of corticotropin releasing factor (CRF) in the brain and probably responsible for most of these activities. The effects of 8 putative neurotransmitters applied iontophoretically to more than 400 mediobasal hypothalamic (MBH) neurons in the rat were examined, and compared with cortisol sensitivity of the same neurons. Glutamate was the only agent that produced excitation exclusively, while GABA, serotonin, glycine and dopamine were inhibitory in action.

Internal cesium ions block various K conductances in spinal motoneurons.

Conventional intracellular recording with low resistance electrodes was used to examine the effects of iontophoretic injections of Cs+ ions (30-200 nA for 30-500 s) into spinal motoneurons of cats anesthetized with pentobarbital and paralyzed with gallamine. The most striking effects of internal Cs+ were a great prolongation of the falling phase of action potentials, a large reduction in the amplitude of their afterhyperpolarizations, and a considerable increase in the size of delayed depolarizations. A reduction of resting membrane conductance (up to half of control values) and a small increase in membrane potential usually were evident.

Modification of responses to sensory and hippocampal stimuli in neurons of the rat mediobasal hypothalamus in the presence of iontophoretically applied cortisol.

The effects of iontophoretic cortisol on evoked activity was studied in rat tuberal hypothalamic units. Evoked activity from visual, auditory, sciatic nerve and hippocampal stimulation was examined in same neurons both before and during local cortisol administration. Hippocampal stimuli were studied in isolation and as conditioning stimuli for one of the sensory modalities.

Post-synaptic conductance increase associated with presynaptic inhibition in cat lumbar motoneurones.

1. Motoneurones were examined in which low-intensity p.b.

The reversal potential as a diagnostic tool in transmitter identification.

The three-ion test still appears to be the best electrophysiological tool available to define the molecular mechanisms involved in activation of a given ionophore. New insights into synaptic mechanisms require the investigator to be alert to possible exceptional cases. In general, the treatment of the exceptional case is validly accomplished once the diagnosis is made.

Intracellular divalent cations and neuronal excitability.

Itracellular injections of Mg into cat spinal motoneurones have a depolarizing action, associated with a fall in input conductance, and depression of the postspike hyperpolarizing after-potential (a.h.p.

Stoichiometry of GABA-receptor interactions: GABA modulates the glycine-receptor interaction allosterically in a vertebrate neuron.

1. Measurement of steady-state conductance changes provides a reliable method for determination of transmitter-receptor stoichiometry in general and for GABA and its receptor interactions in particular. Log-log plotting of steady-state conductance changes as a function of decreasing transmitter concentration gives the molecularity of the interaction as a limiting slope.

Significance of 2,4-dinitrophenol action on spinal motoneurones.

1. Extracellular iontophoretic applications of DNP lead to an increase in the membrane conductance of cat spinal motoneurones, manifested by a rise in input conductance, a slower rate of rise and fall of action potentials, and occlusion of the afterhyperpolarization. 2.

EGTA and motoneuronal after-potentials.

1. Intracellular iontophoretic injections of EGTA (5--20 nA) into cat spinal motoneurones consistently greatly reduce the amplitude of the delayed after hyperpolarization (a.h.