重复电刺激前肢神经引起成年大鼠运动皮层的可塑性改变

为了了解成年大鼠运动皮层的功能可塑性，利用皮层内微刺激方法测定ＭＩ代表区并观察重复电刺激前肢神经对ＭＩ代表区的影响。实验组大鼠（９例）持续１．２－２小时的前肢神经电刺激导致前肢运动区与面部触须运动区边界向ＶＩ方向，移动２６３．３±９０．９μｍ并同时伴有运动阈值的改变；ＦＬ内ＭＴ降低５．０±１３．３μＡ，而在ＶＩ内ＭＴ升高９．６±１１．６μＡ对照组大鼠间隔１．５－２小时的两次测定结果，ＦＬ－ＶＩ边界     

Altered EphA5 mRNA expression in rat brain with a single methamphetamine treatment

Methamphetamine is a potent and indirect dopaminergic agonist which can cause chronic brain dysfunctions including drug abuse, drug dependence and drug-induced psychosis. Methamphetamine is known to trigger molecular mechanisms involved in associative learning and memory, and thereby alter patterns of synaptic connectivity. The persistent risk of relapse in methamphetamine abuse, dependence and psychosis may be caused by such alterations in synaptic connectivity. EphA5 receptors constitute large families of tyrosine kinase receptor and are expressed almost exclusively in the nervous system, especially in the limbic structures. Recent studies suggest EphA5 to be important in the topographic projection, development, and plasticity of limbic structures, and to be involved in dopaminergic neurotransmission. We used in situ hybridization to examine whether methamphetamine alters EphA5 mRNA expression in the brains of adult male Wister rats. EphA5 mRNA was widely distributed in the medial frontal cortex, cingulate cortex, piriform cortex, hippocampus, habenular nucleus and amygdala. Compared to baseline expression at 0 h, EphA5 mRNA was significantly decreased (by 20%) in the medial frontal cortex at 24 h, significantly increased (by 30%) in the amygdala at 9 and 24 h, significantly but transiently decreased (by 30%) in the habenular nucleus at 1 h after a single injection of methamphetamine. Methamphetamine did not change EphA5 mRNA expression in the cingulate cortex, piriform cortex or hippocampus. Our results that methamphetamine altered EphA5 mRNA expression in rat brain suggest methamphetamine could affect patterns of synaptic connectivity, which might be responsible for methamphetamine-induced chronic brain dysfunctions.     

Mechanisms of compensation for vestibular deficits in the frog

Summary In hemilabyrinthectomized frogs excitatory responses of central vestibular neurons to electrical stimulation of the remaining vestibular nerve were recorded extra- and intracellularly at different stages (0, 3, and 60 days) after the operation.The output pattern of ipsilateral vestibular neurons sending an axon across the midline via the vestibular commissure to the deafferented nucleus did not change postoperatively.The synaptic efficacy of these commissural axons ending on partially deafferented vestibular neurons on the lesioned side increased with time. This enhanced synaptic potency was associated with a shortening in time to peak and duration and an increase in amplitude of the evoked EPSPs. As a result most vestibular neurons were readily excited by single shock stimulation of the contralateral vestibular nerve, a finding which was rarely observed in control animals.These plastic changes are explained by the assumption of reactive synaptogenesis. The consequences of this modification for the readjustment of static and dynamic vestibular reflexes are discussed.     

Plasticity of the central nervous system—a neurosurgeon's experience of cerebral compensation and decompensation

Summary Cerebral plasticity constitutes one of the most decisive factors in recovery and readaptation after cerebral lesions. In contrast to the considerable progress in current studies on normal neuronal plasticity including the idea of l'homme neuronal, the concept of plasticity postulated by Albrecht Bethe in 1929 received little attention. The author, as a neurosurgeon, has tried to describe cranial morphological plasticity, morphological and functional plasticity in infantile encephalopathies and especially in hemiatrophic lesions. It is supposed that a true morphological substrate exists due to compensatory hyperplasia of the uninvolved hemisphere.Modern neurosurgical techniques have demonstrated that the functional plastic capacity is much larger than has been supposed, even in the elderly. Some aspects of the mechanisms of compensation and decompensation of cortical and subcortical structures as well as of the central regulation systems are discussed. The full extent of the amazing recovery and functional reorganization is reached by plastic capacity, personal motivation, adequate training and sufficient time.The contribution ends with an exposition of a personal philosophy concerning psycho-somatic dualism, the body-mind problem, the future of the human brain and the ethical outlook, based on the progressive biological evolution of the basal neocortex and the immanent functional development (H. Spatz).In grateful memory of my paternal friends, the great German brain researchers Julius Hallervorden (1882–1965) and Hugo Spatz (1888–1969).     

The topography of expanded uncrossed retinal projections following neonatal enucleation of one eye: differing effects in dorsal lateral geniculate nucleus and superior colliculus

The topographic organization of the uncrossed retinal projections to the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) was studied in normal adult hooded rats and in rats subjected to unilateral ocular enucleation on the day of birth. Sections were stained for anterograde degeneration products following discrete retinal lesions at various locations. The projection from the temporal crescent to the dLGN in neonatally enucleated rats had an expanded but topographically normal organization, with the nasotemporal and dorsoventral retinal axes displaying polarities identical to those in normal adults. Neonatal enucleation permits the remaining uncrossed retinogeniculate projection to extend primarily along the "lines of projection" into neuropil normally recipient of binocularly conjugate crossed projections. In the SC, the dorsoventral axis of the temporal crescent showed a normal polarity, but the nasotemporal axis failed to display any topographic organization. Retinal loci in the temporal crescent projected throughout the rostrocaudal extent of the ipsilateral SC. Retinal lesions placed outside the temporal crescent failed to produce any substantial degeneration in ipsilateral dLGN or SC. These topographically distinct effects in dLGN and SC following unilateral eye removal on the day of birth are discussed in the context of differing constraints upon axonal ingrowth and connectivity during early development, which may normally bring about the characteristically distinct features of retinogeniculate and retinocollicular organization.     

Expression of the axon growth-related neural adhesion molecule TAG-1/axonin-1 in the adult mouse brain

 TAG-1/axonin-1 is a neuronal cell adhesion molecule of the immunoglobulin superfamily. It is predominantly expressed during neural development and has been reported to be involved in axonal growth and pathfinding. Here, the expression of TAG-1/axonin-1 was investigated anatomically in the adult mouse brain by in situ hybridization using digoxigenin-labeled cRNA probes. Low levels of TAG-1/axonin-1 could be detected in cerebellar granule cells, in tufted and mitral cells of the olfactory bulb, and in pyramidal cells of area CA1 and CA3 of the hippocampus. We suspect that the expression of TAG-1/axonin-1 in these structures of the adult brain may serve neural plasticity. Accepted: 8 September 1997     

Synaptic Connections of Different Strength Between Wind-sensitive Hairs and an Identified Projection Interneuron in the Locust

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.     

Comparison of Effects of Various Types of NA and 5-HT Agonists on Transmission from Group II Muscle Afferents in the Cat

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, alpha-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 alpha2 adrenoceptors in the intermediate zone/ventral horn and 5-HT1A serotonin receptors in the dorsal horn.     

Fibroblast Growth Factor Enhances Long-term Potentiation in the Hippocampal Slice

Recently we reported that perfusion of hippocampal slices with epidermal growth factor (EGF) lead to enhancement of potentiated responses after tetanic stimulation. In the present study we report that basic fibroblast growth factor (FGF) can also lead to an enhancement of potentiated responses. FGF is a mitogen for several cell types and exhibits neurotrophic effects on neurons of the central nervous system (CNS). Rat hippocampal slices were perfused with FGF at a concentration of 10-9 M. During extra- and intracellular recordings in the CA1-region, the addition of FGF to the perfusing medium produced no change in evoked responses if single pulse or paired pulse stimulation was used. Furthermore FGF had no influence on the resting membrane potential and input resistance. However, after tetanic stimulation, FGF-treated slices showed an increase in the magnitude of potentiation compared to control slices. Taken together with the EGF data these results support the hypothesis that growth factors like FGF with neurotrophic potential on CNS-neurons can influence synaptic efficacy. Furthermore these results show that factors which are able to modulate developmental plasticity and regenerative plasticity can also modulate synaptic plasticity.     

Presynaptic inhibition of synaptic transmission in the rat hippocampus by activation of muscarinic receptors: involvement of presynaptic calcium influx

1. Modulation of presynaptic voltage-dependent calcium channels (VDCCs) by muscarinic receptors at the CA3–CA1 synapse of rat hippocampal slices was investigated by using the calcium indicator fura-2. Stimulation-evoked presynaptic calcium transients ([Ca_pre]_t) and field excitatory postsynaptic potentials (fe.p.s.ps) were simultaneously recorded. The relationship between presynaptic calcium influx and synaptic transmission was studied.
2. Activation of muscarinic receptors inhibited [Ca_pre]_t, thereby reducing synaptic transmission. Carbachol (CCh, 10 μM) inhibited [Ca_pre]_t by 35% and reduced fe.p.s.p. by 85%. The inhibition was completely antagonized by 1 μM atropine. An approximate 4^th power relationship was found between presynaptic calcium influx and postsynaptic responses.
3. Application of the N-type VDCC-blocking peptide toxin ω-conotoxin GVIA (ω-CTx GVIA, 1 μM) inhibited [Ca_pre]_t and fe.p.s.ps by 21% and 49%, respectively, while the P/Q-type VDCC blocker ω-agatoxin IVA (ω-Aga IVA, 1 μM) reduced [Ca_pre]_t and fe.p.s.ps by 35% and 85%, respectively.
4. Muscarinic receptor activation differentially inhibited distinct presynaptic VDCCs. ω-CTx GVIA-sensitive calcium channels were inhibited by muscarinic receptors, while ω-Aga IVA-sensitive channels were not. The percentage inhibition of ω-CTx GVIA-sensitive [Ca_pre]_t was about 63%.
5. Muscarinic receptors inhibited presynaptic VDCCs in a way similar to adenosine (Ad) receptors. The percentage inhibition of ω-CTx GVIA-sensitive [Ca_pre]_t by Ad (100 μM) was about 59%. There was no significant inhibition of ω-Aga IVA-sensitive channels by Ad. The inhibitions of [Ca_pre]_t by CCh and Ad were mutually occlusive.
6. These results indicate that inhibition of synaptic transmission by muscarinic receptors is mainly the consequence of a reduction of the [Ca_pre]_t due to inhibition of presynaptic VDCCs.