Journal de physiologie最新文献

1.) By extracellular and intracellular recordings of the red nucleus (RN) cell activity, we investigated enhancement of signaling effectiveness at the cortico-rubral synapses underlying the establishment of classical conditioning mediated by RN in the cat. The classical conditioning of forelimb flexion was produced by pairing the conditioned stimulus (CS) to the cerebral peduncle (CP) with the unconditioned stimulus (US) to the forelimb skin at an interval of 100 msec for about a week. 2.) The increased responsiveness of RN cells to the CS was correlated with acquisition of the conditioned forelimb flexion, i.e. RN cells responded to the CS with higher firing probability in the animals which received the paired conditioning than those in the animals which received the CS alone or pairing of the CS and the US at random intervals or those in the naive animals which did not receive any training. 3.) Monosynaptic excitation of RN cells in response to the single pulse to CP was most enhanced in the animals which received the paired conditioning. By contrast, response of RN cells, as well as the behavioral response, induced by stimulation of the cerebellar interpositus nucleus (IP) was not enhanced after the paired conditioning. The difference between the responses to the stimulation of CP and IP suggested that the primary site of neuronal change is the cortico-rubral synapses. 4.) In the animals that received the paired conditioning, the excitatory postsynaptic potentials (EPSPs) induced by stimulation of CP had fast-rising components superimposed on the normal slow-rising EPSPs. On the other hand, most of the CP-EPSPs recorded in the naive animals showed a slow time course. The slow time course of the CP-EPSPs has been attributed to the peripheral localization of the cortico-rubral synapses on the dendrites of RN cells. 5.) The electrotonic length of RN cells in the animals which received the paired conditioning was not shorter than that in the naive animals. Therefore, it was suggested that the appearance of the fast-rising component in the CP-EPSPs is cause by formation of the new cortico-rubral synapses on proximal portions of the soma-dendritic membrane of RN cells. 6.) Since it has been established that new synapses formed by collateral sprouting are retained for more than several months, the formation of new synaptic connections could underlie long-lasting behavioral modification.

1.) This paper further explores the feasibility of a model for long-term memory (Lisman, 1985; Lisman and Goldring, 1988). According to this model, the value of synaptic efficacy of individual synapses is stored locally by the group of Ca2+/calmodulin-dependent protein kinase II molecules contained within the post-synaptic density. 2.) Calculations presented in a previous paper indicate that it is feasible for these kinase molecules to encode information with the stability required for long-term memory. These calculations were based on the assumption that the 30 phosphorylation sites on the enzyme are phosphorylated in a serial fashion, i.e. that the sites are not independent. This paper presents similar calculations based on the alternative assumption that the sites are phosphorylated independently. 3.) Kinase molecules that have been switched "on" undergo a continuous process of dephosphorylation and rephosphorylation. Estimates of the energy consumed by this cycle indicate that the energy required would not make unreasonable demands on neuronal metabolism. The necessity of energy consumption by molecular switches is discussed. 4.) The rate of intramolecular autophosphorylation of the Ca2+/calmodulin dependent kinase implies that the cytoplasmic free Ca2+ concentration must stay elevated for several seconds in order for kinase molecules to switch "on". How such a sustained rise in Ca2+ might be achieved is discussed. 5.) An alternative view is that long-term memory storage involves a change in gene expression. The principal evidence supporting this view is the effect of protein synthesis inhibitors on memory. A model is presented showing that the observed effect of protein synthesis inhibitors does not necessarily imply that information storage is at the level of gene expression. 6.) The distinction between "presynaptic" and "postsynaptic" associative learning mechanisms is discussed. It is concluded that this distinction can be misleading and that the possibility that the underlying mechanisms are similar should not be excluded.

This paper gives a short historical summary of how the second messenger concept, introduced by Earl Sutherland some three decades ago, has been refined and applied by neurobiologists to account for long-lasting changes in the membrane properties of certain neurons. Such refinements in the second messenger hypothesis have application to two specific long-lasting changes in neurons in Aplysia. In the bag cell neuroendocrine system, a brief synaptic input induces an afterdischarge lasting about 30 minutes. Both cAMP-dependent and Ca2+ and phospholipid-dependent protein kinases are activated by the synaptic input and a variety of potassium and calcium channels are modulated. In the eye of Aplysia a spontaneous circadian modulation of ion channels takes place over a twenty-four hour period. In addition phase shifts of this circadian oscillator are mediated, for light by cGMP and for serotonin by cAMP. The circadian oscillator, unlike the bag cell afterdischarge mechanism, is sensitive to ionizing radiation as well as to transcriptional inhibitors. Evidence is presented that specific proteins are synthesized at different times in the circadian cycle. One of these proteins (m.w. 41.9, pI 5.5) accumulates linearly with time of day, resembling a sawtooth oscillator. This protein may be the driver for the circadian oscillation itself. The role of second messengers in various forms of plasticity in neuronal systems (sensitization, long-term potentiation, long-term depression, "learning") may just be part of a very widespread mechanism by which neurons and other cells can generate long-lasting changes in membrane and other cellular properties with brief inputs (synaptic, hormonal) that are of some special adaptive value to the organism.

1.) Application of serotonin to Aplysia sensory neurons can result in facilitated synaptic transmission, both short- and long-term. This facilitation is likely to be produced by a complex set of molecular mechanisms: serotonin activates adenylate cyclase, increasing cAMP and protein kinase (Cedar and Schwartz, 1972); serotonin also changes the subcellular distribution of the Ca2+/calmodulin-dependent protein kinase (Saitoh and Schwartz, 1983). Recently, phorbol esters also have been shown to produce facilitation. We have therefore investigated how protein kinase C (PKC) participates in serotonin-mediated synaptic facilitation. 2.) We found that the Aplysia genome encodes PKC, which is expressed in nervous tissue as at least two abundant transcripts (about 0.003% of the total message). Its inferred amino acid sequence is 85% homologous to that of enzymes from mammals and Drosophila, and over 95% homologous if compared to both. The specific activity of the Aplysia kinase is comparable to that found in rat brain, with similar reaction parameters and dependencies on phosphatidylserine (PS), Ca2+, diacylglycerol and phorbol esters. While PKC is found on neuronal membrane in the basal state, the PKC activators, Ca2+ and phorbol esters, further translocate the kinase to membrane in crude extracts of neuronal tissue. The amounts of membrane-bound PKC, as determined by 3H-phorbol-ester binding, are greatest in neuropil and nerve. 3.) Exposure of sensory neurons and their terminals in Aplysia pleural-pedal ganglia to facilitating doses of either phorbol ester or serotonin results in the translocation of PKC from cytosol to membrane, activating the enzyme. cAMP does not produce this translocation.(ABSTRACT TRUNCATED AT 250 WORDS)

Classical conditioning of the gill withdrawal reflex can be demonstrated in two different in vitro Aplysia preparations. The data obtained show that as conditioning of the gill withdrawal reflex proceeds there are changes in synaptic efficacy at the central sensory-motor neurone synapse. These changes in synaptic efficacy, however, are not necessary nor are they sufficient for the observed changes in gill reflex behaviour. Changes must be occurring at other loci within the nervous system to mediate the associative learning. We hypothesized, based on data obtained from one type of in vitro preparation, that changes occur in the ability of the motor neurone to elicit a gill withdrawal response as a result of classical conditioning training. In order to test this hypothesis we depolarized an identified gill motor neurone before and after classical conditioning and found that the motor neurone's ability to elicit a gill movement was facilitated following classical conditioning training. In control preparations that received an explicitly unpaired stimulus paradigm (which does not lead to classical conditioning of the reflex) there was a decrease in the efficacy of a gill motor neurone to elicit a gill withdrawal response. There are a number of possible sites within the integrated central (CNS) and peripheral (PNS) nervous systems where changes could occur to bring about the alterations in motor neurone efficacy. Our results suggest that changes in neuronal activity which underlie learning occur at multiple sites within the nervous system and that a complete understanding of the mechanisms of associative learning can only be obtained when all of these sites are taken into account.

In order to study the role of the renal pelvis on urea sparing in sheep fed low protein diets, the pelvis was perfused through the ureter with 1M and 3M urea solutions. Eight ewes were used: four on a regular diet (total nitrogen 188.7 g.kg-1 dry matter) and the other four on a low protein diet (total nitrogen 109.4 g.kg-1 dry matter). On each animal, perfusions were performed on one kidney; the other one was kept as a control. Fractional excretion of urea (TEu) and urea (Cu), inulin, para-aminohippurate and osmolar clearances, were determined during five experimental periods of 30 min each (T = control, 1M = perfusion with 1M urea solution, R1 = first period of recovery, 3M = perfusion with 3M urea solution, R2 = second period of recovery). 1. During control periods sheep on low protein diet have a greater capacity of urea retention than sheep on regular diet, under antidiuretic conditions (inulin U/P = 200). The following data (means +/- S.D.) are all reduced in animals on low protein diet: TEu by 36% (0.38 +/- 0.19 vs. 0.59 +/- 0.28 for normal protein sheep, p less than 0.05), Cu by 55% (0.50 +/- 0.19 vs. 1.15 +/- 0.49 ml.min-1.kg-1 for normal sheep, p less than 0.01) and amount of urea excreted by 80% (2.1 +/- 0.7 vs. 10.4 +/- 2.7 mg.min-1 for normal sheep, p less than 0.01). 2. The linear regression analysis of the relationship between tubular reabsorption of urea and its filtered amount shows that the capacity of urea retention is significantly higher in low protein sheep and that the difference between the two groups is greater as the filtered amount increases. Following 1M and 3M perfusions, the capacity of urea reabsorption by the perfused kidneys is significantly decreased in low protein animals whereas there is no change in the normal ones. The result is that perfused kidneys of the low protein sheep increase the amount of urea excreted during these periods: urine concentration of urea (Uu) increases by 55% during R1 and by 144% during R2, TEu increases by 60% during R1 and by 147% during R2 and Cu increases by 40% during R1 and by 95% during R2, without any variation of urine flow rate. These changes could be understood, provided that an important transfer of the perfused urea to the renal medulla in the low protein sheep would reduce the concentration gradients which enhance urea passive reabsorption from the collecting ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

The olfactory system is favorable for studying mechanisms of development, plasticity and regeneration. Monoclonal antibodies have been generated which differentially stain olfactory axons and can identify their earliest trajectories in the fetal rat. The developing olfactory pathway also shows differential metabolic activity, as revealed by the 2-deoxyglucose method, and these patterns show plasticity as judged by both physiological and behavioral measures. The sensory neurons undergo dieback and neurogenesis following axonal transection; electrophysiological methods are being used to reveal the membrane mechanisms underlying this unique capacity.

1.) This review considers factors that produce systematic variations in the amplitude of monosynaptic group Ia EPSPs in triceps surae alpha-motoneurons belonging to different motor unit types. 2.) Anatomical studies using horseradish peroxidase to label functionally-identified group Ia afferents and motoneurons postsynaptic to them, and combined anatomicalelectro-physiological studies of type-identified alpha-motoneurons, have constrained some of the factors that produce variations in peak Ia EPSP amplitude in different cells. 3.) Computer modeling studies based on these experimental data, together with other evidence in the literature, suggest that the major factor that produces systematic variation in Ia EPSP amplitudes in type FF, FR, and S motoneurons is a corresponding variation in the density of active group Ia synapses. 4.) Although EPSP amplitudes are also affected by the relative conductance of the somatic membrane, as reflected in the dendritic-to-somatic conductance ratio, it is possible that at least some of this influence is an artifact produced by microelectrode penetration.

We describe a new surgical technique of duodenectomy whose main step is the enucleation of the duodenum. The advantage of this technique is that it prevents occurrence of bleeding and thus the use of too many ligatures. Consumption, growth and reproduction performances were normal in the duodenectomized animals.

Experiments were performed in forty-five cats anaesthetized with alpha-chloralose. The aim of the study was to investigate a sample of primary muscle spindle afferents from triceps muscle with respect to their fusimotor reflex control from ipsi- as well as contralateral hind limb. Primary muscle spindle afferents of the triceps surae muscle were recorded from the mean rate of firing and the modulation of the afferent response to sinusoidal stretching of the triceps surae muscle was determined. Test measurements were made during tonic stretch of the ipsilateral PBSt, contralateral PBSt, contralateral triceps muscle or during extension of the intact contralateral hind limb. Control measurements were made with ipsi- and contralateral PBSt as well as contralateral triceps muscles relaxed and with contralateral hind limb in resting position. The occurrence and types of fusimotor effects were assessed by comparing test to control responses. The main finding of the present investigation was the great variability in type and size of the fusimotor effects evoked by different ipsi- and contralateral reflex stimuli. Both ipsi- and contralateral stimulations gave rise to predominantly dynamic, predominantly static or mixed static and dynamic fusimotor reflexes. In the same preparation, a given reflex stimulus often caused different reflex responses in different triceps surae primary spindle afferents. In the same afferent unit, different reflex stimuli usually produced fusimotor effects which differed from each other in type and/or size. In general, contralateral whole limb extension and stretch of contralateral PBSt muscles were more potent as reflex stimuli than stretch of the ipsilateral PBSt muscle. Stretch of the contralateral triceps surae muscle was, but for a few afferent units, ineffective as reflexogenic stimulus. It is concluded that the individualized receptive profiles of the primary muscle spindle afferents, which have been postulated in earlier investigations where the effects of different stimuli have been investigated on different cell populations, still seems to hold good when the stimuli are tested on the same units. The individuality of the receptive profiles of gamma-motoneurones is discussed in relation to different motor control hypotheses.