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PubMed1990

Kinase activity associated with caldesmon is Ca2+/calmodulin-dependent kinase II.

The relationship of the kinase which co-purifies with caldesmon to Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II) was investigated by studying the phosphorylation of bovine brain synapsin I, as well-characterized substrate of CaM-kinase II. Synapsin I is a very good substrate (Km = 90 nM) of the co-purifying kinase, which phosphorylates two sites in synapsin I, both of which are distinct from the single site phosphorylated by cyclic-AMP-dependent protein kinase. Phosphorylation of synapsin I is Ca2(+)- and calmodulin-dependent: half-maximal activation occurs at 0.13 microM-Ca2+ and maximal activity at 0.4 microM-Ca2+. Phosphorylation of the co-purifying kinase slightly enhances the rate, but does not alter the stoichiometry, of subsequent synapsin I phosphorylation; it does, however, circumvent the requirement for Ca2+ and calmodulin. The properties of this kinase therefore closely resemble those of CaM-kinase II, and we conclude that it is probably a smooth-muscle isoenzyme of CaM-kinase II.

Animals↗
PubMed1984

Free cytoplasmic Ca2+ and neurotransmitter release: studies on PC12 cells and synaptosomes exposed to alpha-latrotoxin.

The relationship between the free cytoplasmic Ca2+ concentration, [Ca2+]i, and neurotransmitter release was investigated in guinea pig brain synaptosomes and the neurosecretory cell line PC12. Release was induced by alpha-latrotoxin, which acts in both Ca2+ -containing and Ca2+ -free incubation media, or by the classical depolarizing agents high K+ and veratridine, which require extracellular Ca2+. Two complementary approaches were used to reveal changes of [Ca2+]i: (i) direct measurement by a fluorescent Ca2+ indicator (quin2) and (ii) study of the Ca2+ -dependent phosphorylation of a protein, synapsin I, located at the cytoplasmic surface of synaptic vesicles. Depolarizing agents, when applied in Ca2+ -containing medium, induced the [Ca2+]i to increase promptly 3- to 6-fold, drastically increased synapsin I phosphorylation, and caused stimulation of transmitter release. With alpha-latrotoxin, the [Ca2+]i increase was delayed and occurred at a slower rate, the increase of synapsin I phosphorylation was less drastic, and the release response was much more pronounced. In Ca2+ -free medium, depolarizing agents released no transmitter and had no effect on [Ca2+]i or synapsin I phosphorylation, whereas with alpha-latrotoxin these processes were dissociated: considerable stimulation of the release without apparent change of [Ca2+]i and synapsin I phosphorylation. We conclude that the relationship between average [Ca2+]i and transmitter release is not straightforward and, in particular, that the release evoked by alpha-latrotoxin in Ca2+ -free medium is mediated by a factor(s) other than bulk redistribution of Ca2+ from intracellular stores.

Aminoquinolines↗
PubMed2000

Use of phosphosynapsin I-specific antibodies for image analysis of signal transduction in single nerve terminals.

We have developed a semi-quantitative method for indirectly revealing variations in the concentration of second messengers (Ca(2+), cyclic AMP) in single presynaptic boutons by detecting the phosphorylation of the synapsins, excellent nerve terminal substrates for cyclic AMP- and Ca(2+)/calmodulin-dependent protein kinases. For this purpose, we employed polyclonal, antipeptide antibodies recognising exclusively synapsin I phosphorylated by Ca(2+)/calmodulin-dependent protein kinase II (at site 3) or synapsins I/II phosphorylated by either cAMP-dependent protein kinase or Ca(2+)/calmodulin-dependent protein kinase I (at site 1). Cerebellar granular neurones in culture were double-labelled with a monoclonal antibody to synapsins I/II and either of the polyclonal antibodies. Digitised images were analysed to determine the relative phosphorylation stoichiometry at each individual nerve terminal. We have found that: (i) under basal conditions, phosphorylation of site 3 was undetectable, whereas site 1 exhibited some degree of constitutive phosphorylation; (ii) depolarisation in the presence of extracellular Ca(2+) was followed by a selective and widespread increase in site 3 phosphorylation, although the relative phosphorylation stoichiometry varied among individual terminals; and (iii) phosphorylation of site 1 was increased by stimulation of cyclic AMP-dependent protein kinase but not by depolarisation and often occurred in specific nerve terminal sub-populations aligned along axon branches. In addition to shedding light on the regulation of synapsin phosphorylation in living nerve terminals, this approach permits the spatially-resolved analysis of the activation of signal transduction pathways in the presynaptic compartment, which is usually too small to be studied with other currently available techniques.

Animals↗
PubMed1985

The expression and localization of synaptic vesicle antigens at neuromuscular junctions in vitro.

To examine the biochemical differentiation of presynaptic nerve terminals in vitro, we studied the expression and localization at synapses of two synaptic vesicle-specific antigens, synapsin I and protein p65. We purified these proteins from brain and raised a rabbit antiserum against each of them. Chick synapsin I had a slightly smaller molecular weight than its mammalian homologue, although the two share several properties. With the anti-p65 serum, the protein p65 could be detected consistently in presynaptic terminals at the neuromuscular junction in vivo, as had been previously shown for synapsin I. These antisera proved sufficiently sensitive to allow a study of the developmental expression of the antigens in embryonic chick brain, using protein blots. The two antigens are not coordinately regulated; protein p65 was detected substantially sooner in development that was synapsin I. Both synapsin I and protein p65 are expressed by ciliary ganglion neurons in vitro, as assessed by immunofluorescence using the affinity-purified antisera. The two antigens co-localized at all times in culture. Neurons grown alone were reliably stained only after 4 to 5 days in culture, but comparable levels of staining were found after 1 day when neurons were co-cultured with embryonic myotubes. In the co-cultures, staining was initially high in growth cones and neurites, but the brightest staining became confined to sites of nerve-muscle contact over 4 to 5 days in culture. In mature cultures, patches of bright staining for the vesicle antigens coincided with patches of acetylcholine receptors, suggesting that the antigens had become localized at synapses. The time course of this localization process suggests that it corresponds to the morphological maturation of synapses. It should be possible to exploit this system to obtain information about the molecules and processes involved in the induction of presynaptic differentiation.

Animals↗
PubMed1989

Calcitonin gene-related peptide and chromogranin A: presence and intra-axonal transport in lumbar motor neurons in the rat, a comparison with synaptic vesicle antigens in immunohistochemical studies.

The presence and intra-axonal transport of calcitonin gene-related peptide and chromogranin A were investigated in motor neurons belonging to the rat sciatic nerve. Their co-localization with markers of cholinergic organelles (SV2, p38, and synapsin I) was also investigated, using immunofluorescence techniques, including double labelling experiments. It was found that motor perikarya in the lumbar spinal cord contained calcitonin gene-related peptide-like immunoreactivity and chromogranin A-like immunoreactivity, and probably also caligulin-like immunoreactivity, located in the Nissl substance of the cytoplasm. Also, some SV2 (detected by the monoclonal antibody 10H) was present in some motor neuron perikarya, but most often these were devoid of SV2 and p38, as well as of synapsin I-like immunoreactivity. These three antigens were, on the other hand, concentrated in nerve terminals in the entire gray substance of the spinal cord. In the ventral root, after crushing, calcitonin gene-related peptide, chromogranin A, synapsin I, SV2, p38 and caligulin-like immunoreactivity accumulated in thick and medium-sized axons proximal to the crush, while only antisera against SV2 and p38 labelled accumulated material distal to the crush. In the sciatic nerve, the same essential picture was observed as in the ventral root, but here two other nervous components were also present in the normal sciatic nerve, i.e. peripheral branches of the sensory system and axons of the sympathetic system. By various denervation procedures, it was demonstrated that most calcitonin gene-related peptide-like immunoreactivity and almost all chromogranin A-like immunoreactivity, accumulating in thick axons proximally, emanated from the ventral root. Thin and medium-sized axons originated from the sensory and sympathetic systems and contributed to accumulations both proximally and distally to the crush. Synapsin I-like immunoreactive material accumulated only proximal to the crush, while SV2 and p38-like material accumulated bidirectionally in axons of all sizes. In motor endplates of the rat diaphragm and gastrocnemic muscle, no calcitonin gene-related peptide-like material was observed. However, some chromogranin A-like immunoreactivity was present, in addition to large amounts of synapsin I-like, p38-like and SV2-like material, which had a finely granular appearance and was concentrated near the presynaptic membrane of the nerve terminal endfeet, where synaptic vesicles are known to be located.

Animals↗
PubMed1984

Mammalian brain phosphoproteins as substrates for calcineurin.

Calcineurin, a Ca2+/calmodulin-dependent phosphoprotein phosphatase found in several tissues, is highly concentrated in mammalian brain. In an attempt to identify endogenous brain substrates for calcineurin, kinetic analyses of the dephosphorylation of several well-characterized phosphoproteins purified from brain were performed. The proteins studied were: G-substrate, a substrate for cyclic GMP-dependent protein kinase; DARPP-32, a substrate for cyclic AMP-dependent protein kinase; Protein K.-F., a substrate for a cyclic nucleotide- and Ca2+-independent protein kinase; and synapsin I, a substrate for cyclic AMP-dependent (site I) and a Ca2+/calmodulin-dependent protein kinase (site II). Calcineurin dephosphorylated each of these proteins in a Ca2+/calmodulin-dependent manner. Similar Km values were obtained for each substrate: G-substrate, 3.8 microM; DARPP-32, 1.6 microM; Protein K.-F., approximately 3 microM (S0.5); synapsin I (site I), 7.0 microM; synapsin I (site II), 4.4 microM. However, significant differences were obtained for the maximal rates of dephosphorylation. The kcat values were: G-substrate, 0.41 s-1; DARPP-32, 0.20 s-1; Protein K.-F., 0.7 s-1; synapsin I (site I), 0.053 s-1; synapsin I (site II), 0.040 s-1. Comparisons of the catalytic efficiency (kcat/Km) for each substrate indicated that DARPP-32, G-substrate, and Protein K.-F. are all potential substrates for calcineurin in vivo.

Animals↗
PubMedDate not supplied

Organelles in fast axonal transport. What molecules do they carry in anterograde vs retrograde directions, as observed in mammalian systems?

The present minireview describes experiments carried out, in short-term crush-operated rat nerves, using immunofluorescence and cytofluorimetric scanning techniques to study endogenous substances in anterograde and retrograde fast axonal transport. Vesicle membrane components p38 (synaptophysin) and SV2 are accumulating on both sides of a crush, but a larger proportion of p38 (about 3/4) than of SV2 (about 1/2) is recycling toward the cell body, compared to the amount carried with anterograde transport. Matrix peptides, such as CGRP, ChRA, VIP, and DBH are recycling to a minor degree, although only 10-20% of surface-associated molecules, such as synapsins and kinesin, appear to recycle. The described methodological approach to study the composition of organelles in fast axonal transport, anterograde as compared to retrograde, is shown to be useful for investigating neurobiological processes. We make use of the "in vivo chromatography" process that the fast axonal transport system constitutes. Only substances that are in some way either stored in, or associated with, transported organelles can be clearly observed to accumulate relative to the crush region. Emphasis in this paper was given to the synapsins, because of diverging results published concerning the degree of affiliation with various neuronal organelles. Our previously published results have indicated that in the living axons the SYN I is affiliated with mainly anterogradely fast transported organelles. Therefore, some preliminary, previously unpublished results on the accumulations of the four different synapsins (SYN Ia, SYN Ib, SYN IIa, and SYN IIb), using antisera specific for each of the four members of the synapsin family, are described. It was found that SYN Ib clearly has a stronger affiliation to anterogradely transported organelles than SYN Ia, and that both SYN IIa and SYN IIb are bound to some degree to transported organelles.

Animals↗
PubMed1990

Some nerve endings in the rat pelvic paracervical autonomic ganglia and varicosities in the uterus contain calcitonin gene-related peptide and originate from dorsal root ganglia.

The pelvic paracervical autonomic ganglia of female rats were studied for a subpopulation of nerve endings that could be derived from sensory nerve fibers. Immunohistochemical staining using an antiserum against the synaptic-terminal protein synapsin I was used to identify terminal boutons, while an antiserum against the neuropeptide calcitonin gene-related peptide was used to reveal a subpopulation of sensory nerve fibers. The uterine cervix was also examined for the existence of calcitonin gene-related peptide and synapsin I immunoreactivity in nerve fiber varicosities. In addition, the location of nerve endings in the paracervical ganglion was compared to that in the superior cervical ganglion. Synapsin I immunoreactivity was present in the paracervical ganglion in abundant boutons around neuron somata and in the cervix in varicose nerve fibers of the myometrium, vasculature and epithelium. Double labeling immunocytochemistry revealed calcitonin gene-related peptide-like immunoreactivity in subpopulations of synapsin I-immunoreactive endings in ganglia and nerve varicosities in the cervix. Injection of a retrograde axonal tracer, fluorogold, into the paracervical ganglion produced labeled neurons in dorsal root ganglia and spinal cord; however, fluorogold-labeled neurons containing calcitonin gene-related peptide immunoreactivity were visualized only in dorsal root ganglia. Injections of fluorogold into the uterine cervix produced labeled neurons in the paracervical ganglion and dorsal root ganglia; however, only those in dorsal root ganglia contained immunoreactivity for calcitonin gene-related peptide. These results suggest that immunoreactivity for calcitonin gene-related peptide is present in a subpopulation of nerve endings in the paracervical ganglion and not merely in fibers of passage. The nerve endings in the ganglion and varicosities in the uterine cervix originate from sensory neurons in dorsal root ganglia. The arrangement of endings in the ganglia could play a role in sensory/autonomic interactions for modulation of visceral activity.

Animals↗
PubMed2006

Differential development of vesicular glutamate transporters in brain: an in vitro study of cerebellar granule cells.

The cerebellar granule cells have been extensively used for studies on metabolism, neurotransmission and neurotoxicology, since they can easily be grown in cultures. However, knowledge about the development of different proteins essential for synaptic transmission in these cells is lacking. This study has characterized the developmental profiles of the vesicular glutamate transporters (VGLUTs) and the synaptic vesicle proteins synapsins and synaptophysin in cerebellar granule cells and in co-cultures containing both granule cells and astrocytes. The protein levels of VGLUT2 decreased by approximately 70% from days 2 to 7 in vitro, whereas the levels of VGLUT1 increased by approximately 95%. Protein levels of synapsin I, synapsin IIIa and synaptophysin showed a developmental pattern similar to VGLUT1 while synapsin II and VGLUT3 were absent. The mRNA expressions of VGLUT1 and VGLUT2 were in accordance with the protein levels. The results indicate both that cerebellar granule cells are mature at approximately 7 days in vitro, and that the up-regulation of VGLUT1 and down-regulation of VGLUT2 in cerebellar granule cells are both independent of surrounding astrocytes and neuronal input. The results of this study are discussed in relation to general developmental profiles of VGLUTs in other brain regions.

Animals↗
PubMedDate not supplied

Assessment of PC12 cell differentiation and neurite growth: a comparison of morphological and neurochemical measures.

In vitro techniques are used increasingly to screen for and characterize neurotoxicants. In many cases, chemical-induced injury to developing neurons has been examined in vitro by assessing morphological changes in differentiation and neurite growth. This research evaluated the use of proteins associated with axonal growth and synaptogenesis as surrogates for morphological measurement of neuronal differentiation. PC12 cells, which differentiate upon nerve growth factor (NGF) stimulation, were used as the in vitro model. NGF-induced (50 ng/ml) differentiation (cells with at least one neurite with a length equal to the cell body diameter) and neurite growth (length of longest neurite) were determined using light microscopy and computer-based quantitative image analysis. PC12 cell differentiation and neurite growth reached a plateau after 6 days in culture. Expression of the axonal growth associated protein 43 (GAP-43) and the synaptic protein synapsin I were assessed simultaneously by Western blot during cell differentiation. Expression of GAP-43 was low on Culture Day 0 and increased progressively to maximum levels on Culture Day 5. Likewise, synapsin I expression increased slowly on Days 0-4, and then rapidly on Days 5-7 of culture. Pharmacologic inhibitors of NGF-induced signaling were used to test the sensitivity of the proteins to chemical disruption of differentiation. The MAP kinase inhibitor, U0126 (5-30 microM) and the PKC inhibitor, bisindolylmaleimide I (Bis I; 1.25-5 microM) inhibited differentiation and neurite outgrowth in a concentration-dependent manner. U0126 and Bis I significantly decreased GAP-43, but not synapsin I expression. Interestingly, the PI-PLC inhibitor edelfosine (ET-18; 5-30 microM) stimulated differentiation at early times of exposure followed by a significant decrease in neurite length at later time points. However, ET-18 did not alter the expression of GAP-43 or synapsin I. These data suggest that GAP-43 may be a useful indicator of the status of PC12 cell differentiation.

Animals↗
PubMed1998

Microsphere embolism-induced changes in noradrenaline release in the cerebral cortex in rats.

The present study was undertaken to elucidate pathophysiological changes in noradrenaline release, phosphorylation of synapsin I and ultrastructure of the cerebrocortical nerve terminals following microsphere embolism in rats. In the microdialysis study, K+-stimulated noradrenaline release in the cerebral cortex was not altered on the 1st day but markedly decreased on the 3rd and 7th days after the embolism. Synaptosomes were isolated from the cerebral cortex of the operated animals on the 1st, 3rd and 7th days after the embolism. The level of calmodulin and the phosphorylation of synapsin I in the synaptosomes were not altered up to the 7th day, but the levels of calcium/calmodulin-dependent protein kinase II and synapsin I in the synaptosomes were significantly decreased by microsphere embolism. Electron microscopic study showed no appreciable changes in the structure of the synaptosomes on the 1st day, but a large number of clumps of synaptic vesicles were observed on the 3rd and 7th days after the embolism. These results suggest that microsphere embolism-induced changes in noradrenaline release from nerve terminals are due to a failure in the process following phosphorylation of synapsin I. Aggregation of synaptic vesicles in nerve terminals may contribute to the pathogenesis of microsphere embolism.

Animals↗
PubMed2000

Spectrin (betaSpIIsigma1) is an essential component of synaptic transmission.

The cellular mechanism that underlies the regulated release of synaptic vesicles during neurotransmission is not fully known. Our previous data has shown that brain spectrin (alphaSpIIsigma1/betaSpIIsigma1)2 is localized in axons and nerve terminals and we have shown that the beta subunit (betaSpIIsigma1) contains a synapsin-binding domain capable of interacting with synapsin and small synaptic vesicles in vitro and in vivo. These findings suggested a role for brain beta-spectrin in synaptic neurotransmission. To examine this possibility further, peptide-specific antibodies directed against epitopes within the synapsin-binding domain of brain beta-spectrin, or against flanking regions, were injected into the presynaptic neuron of synaptically paired rat hippocampal neurons in culture. Here, we show that the antibodies directed against the synapsin-binding domain specifically blocked synaptic neurotransmission.

Animals↗
PubMed1996

Effects of synaptic vesicles on actin polymerization.

We have analyzed the effects of synaptic vesicles on actin polymerization by using a time-resolved spectrofluorometric assay. We have found that synaptic vesicles have complex effects on the kinetics of actin polymerization, which vary depending on whether the synaptic vesicle-specific phosphoprotein synapsin I is absent or present on their membrane. Synapsin I bound either to synaptic vesicles or to pure phospholipid vesicles exhibits phosphorylation-dependent actin-nucleating activity. Synaptic vesicles depleted of endogenous synapsin I decrease the rate and the final extent of actin polymerization, an effect which is not observed with pure phospholipid vesicles. Thus, the state of association of synapsin I with synaptic vesicles, which is modulated by its state of phosphorylation, may affect actin assembly and the physico-chemical characteristics of the synaptic vesicle microenvironment.

Actins↗
PubMed1998

Central neuronal synapse formation on micropatterned surfaces.

Controlling synapse formation is a key to patterning of neurons into functional circuits and networks in vitro. However, the process of synapse formation among neurons grown on artificial surfaces is relatively unstudied. We cultured embryonic hippocampal cells on trimethoxysilylpropyl-diethylenetriamine (DETA) and tridecafluoro-1, 1,2,2-tetrahydrooctyl-1-dimethylchlorosilane (13F), and on patterns composed of DETA lines separated by 13F spaces. For comparison, neurons were concurrently plated on surfaces coated with uniform poly-d-lysine (PDL). Pre- and postsynaptic specializations were identified by immunostaining for synapsin I and microtubule-associated protein-2 (MAP-2). Spontaneous (SPCs) and evoked (EPCs) postsynaptic currents were recorded using dual patch-clamp techniques. We found that DETA promoted synapse formation, whereas evidence for synapse formation on 13F was barely detected. MAP-2+ neuronal soma and rapidly growing dendrites were co-localized with synapsin I puncta faithfully along DETA lines. The expression of synapsin I puncta, and MAP-2+ soma and dendrites correlated well with the appearance of SPCs. Synapsin I, MAP-2 and SPCs emerged together at days 3-4 and increased at day 7, when EPCs appeared. Synaptic signals occurring during 4-7 days in culture were all GABAergic. These results indicate that fully functional synapses are formed on silane surfaces, demonstrating the suitability of patterned silane surfaces for organizing synapse formation in vitro.

Animals↗
PubMed2003

A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic factor.

We have conducted studies to determine the potential of dietary factors to affect the capacity of the brain to compensate for insult. Rats were fed with a high-fat sucrose (HFS) diet, a popularly consumed diet in industrialized western societies, for 4 weeks before a mild fluid percussion injury (FPI) or sham surgery was performed. FPI impaired spatial learning capacity in the Morris water maze, and these effects were aggravated by previous exposure of the rats to the action of the HFS diet. Learning performance decreased according to levels of brain-derived neurotrophic factor (BDNF) in individual rats, such that rats with the worst learning efficacy showed the lowest levels of BDNF in the hippocampus. BDNF immunohistochemistry localized the decreases in BDNF to the CA3 and dentate gyrus of the hippocampal formation. BDNF has a strong effect on synaptic plasticity via the action of synapsin I and cAMP-response element-binding protein (CREB), therefore, we assessed changes in synapsin I and CREB in conjunction with BDNF. Levels of synapsin I and CREB decreased in relation to decreases in BDNF levels. The combination of FPI and the HFS diet had more dramatic effects on the active state (phosphorylated) of synapsin I and CREB. There were no signs of neurodegeneration in the hippocampus of any rat group assessed with Fluoro-Jade B staining. The results suggest that FPI and diet impose a risk factor to the molecular machinery in charge of maintaining neuronal function under homeostatic and challenging situations.

Animals↗
PubMed2001

An experimental study on the course of trans-synaptic propagation of neural activity and plasticity in the hippocampus in kainate-induced epilepsy.

To investigate the course of trans-synaptic propagation of neural activity and plasticity in temporal lobe epilepsy, time-dependent changes in the level of synapsin I, a synaptic vesicle protein that is a marker of enhanced synaptic activity and synaptogenesis, were examined following kainate-induced epileptic status in rats. Compared with the control, the level of synapsin I protein increased in the bilateral stratum oriens of CA3 (28.8-40.2%) and CA1 (28.0-34.6%), and the stratum radiatum of CA1 (34.0%) ipsilateral to the injection site at 8 h after intra-amygdala administration of kainate. At 24 h, and 2 and 4 weeks after the kainate treatment, however, synapsin I levels returned to normal levels in most of the regions studied in spite of the extended neural loss in the hippocampus, which suggested the axonal sprouting on the remaining cells. The synapsin I mRNA levels time-dependently decreased bilaterally in CA1-CA3 and the hilus, while no significant changes were observed in the dentate gyrus. These results suggest that the synaptic input to CA3 and CA1 through the stratum oriens was enhanced in this model. A different mode of hippocampal neural activity and plasticity between kainate and kindling models of epilepsy may be stressed.

Animals↗
PubMed1996

Impaired learning in mice with abnormal short-lived plasticity.

BACKGROUND: Many studies suggest that long term potentiation (LTP) has a role in learning and memory. In contrast, little is known about the function of short-lived plasticity (SLP). Modeling results suggested that SLP could be responsible for temporary memory storage, as in working memory, or that it may be involved in processing information regarding the timing of events. These models predict that abnormalities in SLP should lead to learning deficits. We tested this prediction in four lines of mutant mice with abnormal SLP, but apparently normal LTP-mice heterozygous for a alpha-calcium calmodulin kinase II mutation (alpha CaMKII +/-) have lower paired-pulse facilitation (PPF) and increased post-tetanic potentiation (PTP); mice lacking synapsin II (SyII-/-), and mice defective in both synapsin I and synapsin II (SyI/II-/-), show normal PPF but lower PTP; in contrast, mice just lacking synapsin I (SyI-/-) have increased PPF, but normal PTP. RESULTS: Our behavioral results demonstrate that alpha CaMKII +/-, SyII-/- and SyI/II-/- mutant mice, which have decreased PPF or PTP, have profound impairments in learning tasks. In contrast, behavioral analysis did not reveal learning deficits in SyI-/- mice, which have increased PPF. CONCLUSIONS: Our results are consistent with models that propose a role for SLP in learning, as mice with decreased PPF or PTP, in the absence of known LTP deficits, also show profound learning impairments. Importantly, analysis of the SyI-/- mutants demonstrated that an increase in PPF does not disrupt learning.

Animals↗
PubMed2003

Ngfi-a immunoreactivity in the primate retina: implications for genetic regulation of plasticity.

In rodents, enriched environments drive the expression of the immediate early gene NGFI-A, a regulator of the plasticity marker Synapsin I. Both proteins have been implicated as mediators of plasticity in the rat mammalian retina. In the present work immunocytochemistry directed against these proteins was used to explore their basal activity in the retina of a more visual species, the New World monkey Cebus apella. In contrast to rat, monkey retina displayed high basal expression of both NGFI-A and Synapsin I. The greatest number of NGFI-A -expressing cells was observed within the inner nuclear layer, although NGFI-A positive nuclei were also found in the ganglion cell layer. High levels of Synapsin I were found in the inner plexiform layer and outer plexiform layer. Our findings are consistent with the postulate that the retinas of highly visual animals may experience ongoing reorganization as part of normal visual processing, and that NGFI-A and Synapsin I may be well positioned to regulate some of these changes.

Animals↗