Abnormal Synaptic Transmission in the Olfactory Bulb of
Fyn-Kinase-Deficient Mice
Hiromasa Kitazawa1,
Takeshi Yagi2,
Tsuyoshi Miyakawa3,
Hiroaki Niki3, and
Nobufumi Kawai1
1 Department of Physiology, Jichi Medical School, Tochigi 329-04; 2 Laboratory of Neurobiology and Behavioral Genetics, National Institute for Physiology, Okazaki 444; and 3 Laboratory for Neurobiology of Emotion, Brain Science Institute, RIKEN, Hiroasawa, Wakoshi, Saitama 351-01, Japan
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ABSTRACT |
Kitazawa, Hiromasa, Takeshi Yagi, Tsuyoshi Miyakawa, Hiroaki Niki, and Nobufumi Kawai. Abnormal synaptic transmission in the olfactory bulb of Fyn-kinase-deficient mice. J. Neurophysiol. 79: 137-142, 1998. We studied synaptic transmission in the granule cells in the olfactory bulb of the homozygous Fyn (a nonreceptor type tyrosine kinase)-deficient (fynz/fynz) and heterozygous Fyn-deficient (+/fynz) mice by using slice preparations from the olfactory bulb. Stimulation to the lateral olfactory tract and/or centrifugal fibers to the olfactory bulb evoked field excitatory postsynaptic potentials (fEPSPs) in the granule cells. In +/fynz mice, fEPSPs were augmented by bicuculline, a
-aminobutyric acid (GABAA) antagonist and picrotoxin, whereas fEPSPs in fynz/fynz mice were much less sensitive to bicuculline and picrotoxin. Application of D-2-amino-5-phosphonopentanoic acid had no effect but 6-cyano-7-nitroquinoxaline-2,3-dione produced almost complete block of fEPSPs in both +/fynz mice and fynz/fynz mice. (1S, 3R)-1-aminocyclo-pentane-1.3-dicarboxylate, an agonist of metabotropic glutamate receptors caused a similar depression of fEPSPs in both +/fynz and fynz/fynz mice. In +/fynz mice tetanic stimulation to the lateral olfactory tract and/or centrifugal fibers induced N-methyl-D-aspartate (NMDA)-dependent long-term potentiation (LTP) of fEPSPs, whereas LTP was impaired in fynz/fynz mice. Our results demonstrate altered functions of GABAA and NMDA receptors in the olfactory system of Fyn-deficient mice.
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INTRODUCTION |
Fyn, a nonreceptor type tyrosine kinase of the Src family, is strongly expressed in the central nervous system (CNS), suggesting that it plays an important role in brain function. Fyn-deficient mutant mice have a variety of abnormal signs, such as impaired long-term potentiation in the hippocampus, with deficits in spatial learning (Grant et al. 1992
), abnormality in suckling behavior in neonatal mutants (Yagi et al. 1993a
), increased fearfulness and enhanced sensitivity to audiogenic seizures (Miyakawa et al. 1994
, 1995
).
An expression study in which
-galactosidase gene (lacZ) was inserted into fyn revealed that Fyn in neural tissues appears to be developmentally regulated (Yagi et al. 1993a
,b
, 1994
). Staining by X-gal showed that high expression was observed in the olfactory tract, the olfactory epithelium, and optic tract in the late embryonic stage. In 7-day-old Fyn-deficient pups, the modified glomerular complex of the olfactory bulb was abnormal in shape and reduced in size. In adults a high level of fyn expression was observed in olfactory bulb, hippocampus, and cerebellum. These results implied an abnormal function of the olfactory system in Fyn-deficient mice. There has been, however, no report on olfactory synaptic transmission at the cellular level in Fyn-deficient mice.
The present experiment is aimed at studying possible changes in the olfactory system in Fyn-deficient mutant mice by using a slice preparation of the olfactory bulb. Because making slice preparations of the olfactory bulb connected to intact olfactory nerve is difficult, we have made slices of the olfactory bulb with the efferent and afferent fibers to the olfactory cortex. We have compared the synaptic potentials in the olfactory bulb of the homozygous Fyn-deficient (fynz/fynz) with those in heterozygous Fyn-deficient (+/fynz) and wild type mice. We have also studied the effects of pharmacological agents acting on the glutamate and
-aminobutyric acid (GABA) receptors, because many studies have reported glutamatergic and GABAergic transmission in the olfactory bulb (Hayashi et al. 1993
; Jahr and Nicoll 1982
; Trombley and Westbrook 1990
, 1992
; Van de Pol 1995; Wellis and Kauer 1994
).
We have found reduced sensitivity to antagonists ofGABAA receptors and impaired long-term potentiation in the olfactory bulb of Fyn-deficient mice.
 |
METHODS |
Fyn-deficient mice
Fyn-deficient mice were generated by inserting the
-galactosidase gene (LacZ) into the fyn gene as reported previously (Yagi et al. 1993b
, 1994
). In brief, TT2 cells, one of the mouse embryonic stem (ES) cell-lines from F1 embryos between C57BL/6 and CBA mouse strains, were mutated by electroporation of the targeting vector pHFZprNeoDT (a targeting vector for mouse Fyn locus),which is composed of Bglll-Sphl DNA fragment of fyn with the exon 3 locus disrupted by insertion of
-galactosidase (lacZ) and neomycin resistant gene (Neo) and at the 3
end added to diphtheria toxin fragment A gene (DT) for negative selection. G418 resistant homologous recombinant cells were selected and injected into eight cell stage embryos to deliver chimeric mice. Chimeric mice were crossed with C57BL/6, an inbred mouse strain, and heterozygous mice were generated. Heterozygous mice were crossed within themselves and homozygous mice were obtained by the Mendelian rule. By immunoblotting with anti-Fyn antibody, we have confirmed no Fyn protein in the olfactory bulb of the homozygotes. When we performed behavioral and anatomic analyses of Fyn mutant mice, we could not detect any abnormalities in the heterozygotes.
Preparation of the olfactory bulb slice
Mice were anesthetized by ether and decapitated. A block of brain containing the olfactory bulb and a part of the olfactory cortex was dissected out. The block was cut in half at the midline and placed on a plate in the slicer with cut surface down for making the slice. Sagittal sections of the olfactory bulb (400-500 µm width) were cut by a vibratome (Microslicer, Dosaka EM). Usually, slices containing medial part of the olfactory bulb (0.5-1 mm from the midline) were used. The slice was submerged in artificial cerebrospinal fluid containing (in mM) 127 NaCl, 1.5 KCl, 1.24 KH2PO4, 2.4 CaCl2, 1.3 MgSO4, 26 NaHPO4, and 10 glucose, bubbled with 95% O2-5% CO2 and maintained at 36°C.

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| FIG. 1.
Distribution of field excitatory postsynaptic potentials (fEPSP) recorded from olfactory bulb slice. A: schematic diagram of sagittal section of olfactory bulb slice. Stimulating electrode is placed near center of olfactory bulb where lateral olfactroy tract (LOT) and centrifugal fibers (CF) run. a-f: position of recording electrode. b and e: distances of 500 and 1000 µm from stimulating electrode, respectively. Distance between each recording position is 500 µm. B: representative fEPSP traces in an Fyn (a nonreceptor type tyrosine kinase)-deficient hetero (+/fynz) mouse. Paired pulse stimulations with interval of 40 ms were applied. C: similar sample fEPSP traces as in B but from a Fyn-deficient homo (fynz/fynz) mouse. D: example record of field potentials in another +/fynz mouse. Potentials are composed of early negative potentials (*) followed by late negative potentials. Note that paired stimuli with an interval of 40 ms produce a marked facilitation in late potentials but early negative potentials are unchanged.
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Electrophysiological recording
After 2 h of incubation a single slice was transferred to the recording chamber as described in previous work in the laboratory (Tsubokawa et al. 1994
-1996
). The chamber was continuously perfused with bathing solution maintained at 35.0 ± 0.5°C. Bipolar stimulating electrode of Teflon-coated silver wires (50-µm diam tip) was placed on the near part of the lateral olfactory tract, which can easily be seen under the microscope. Glass pipette recording electrode containing five times Krebs without calcium and glucose was placed on a more rostral part of the olfactory bulb. Usually low frequency stimulation (200 µs, 100-150 µA) was applied at 0.08-0.12 Hz. Tetanic stimulation consisted of two trains of 100 pulses at 100 Hz separated by an interval of 20 s. To measure the maximal rate of rise of field excitatory postsynaptic potentials (fEPSP), records were digitized at 10 kHz and analyzed by an on-line computer. Groups of three successively evoked fEPSPs were averaged before calculating the maximal rate of change of potential within a time window selected around the rising phase. The computed slope values were displayed as a constantly updated time series.
Picrotoxin (Sigma) and bicuculline methobromide (Sigma) were used in the experiments. 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, Tocris) and D-2-amino-5-phosphonopentanoic acid (APV, Tocris), (1S,3R)-1-aminocyclo-pentane-1.3-dicarboxylate (1S,3R-ACPD, Tocris) were added to the perfusing solutions.
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RESULTS |
Distribution of the field potential in the olfactory bulb
In total, 85 mice (29 fynz/fynz, 37 +/fynz, and 19 wild type) were used as subjects. No difference was found in the data from wild type and those from +/fynz mice. Schematic diagram of a sagittal section of the olfactory bulb slice is shown in Fig. 1A. We chose the slices containing medial part of the olfactory bulb because relatively stable responses were obtained in these preparations. Stimulating electrode placed near the center of the slice could activate both the lateral olfactory tract (LOT) and centrifugal fibers (CF), inducing various forms of field potentials in the olfactory bulb. It is generally observed that negative field potentials were evoked near the dorsal and the middle part of the olfactory bulb, whereas positive potentials prevailed in the ventral part. Typical examples of field potentials in +/fynz are shown in Fig. 1B. Paired stimuli with the interval of 40 ms were applied at a fixed point and the recording electrode was moved along dorsoventral axis. The late negative field potentials with a marked facilitation were recorded in the dorsal part of the slice (Fig. 1Ba). Amplitude of the negative potentials was increased when the recording electrode was placed near the middle of the slice (Fig. 1Bb). When the recording electrode was moved to the ventral part of the slice the field potentials converted to positive wave, which also showed a facilitation (Fig. 1Bc). We observed phase reversal of the potentials between b and c (data not shown). Similar field potential distribution along dorsoventral axis was obtained at nasal part of the slice (Fig. 1B, d and f), although the amplitude was small because of the distance from the stimulation. We made analysis of the field potential distribution with many other slices and concluded that the positive potentials represent the current source of the negative potentials, which could be originated from the current sink of the granule cells (Rall and Shepherd 1968
).

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| FIG. 2.
Effects of antagonists of GABAA and glutamate receptors on fEPSP in +/fynz (A) and fynz/fynz (B) mice. Time courses of maximal fEPSP slope are plotted. Bicuculline with picrotoxin (BICPTX), D-2amino-5-phosphonopentanoic acid (APV), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were applied to bathing solution ( ). Specimen records taken at times shown on graph and maximal slope of fEPSP calculated as indicated. Each point indicates average with SE (3 slices, n = 3).
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Essentially the same potential distribution was observed in fynz/fynz mice (Fig. 1C, a-f). However, the amplitude was generally smaller than that in +/fynz mice. When we measured the amplitude of fEPSPs evoked by the same stimulus intensity (200 µs, 115 ± 5 µA) with a fixed distance between stimulating and recording electrode (500 µm), the peak negative amplitude was 1.21 ± 0.18 mV (12 slices,n = 12) in +/fynz mice, whereas it was 0.66 ± 0.12 mV (16 slices, n = 16) in fynz/fynz mice, showing a significant difference [P < 0.05, analysis of variance (ANOVA)].
In our slice preparations, stimulation could activate both LOT and CF to the olfactory bulb neurons and evoked field potentials generally consisted slow negative potentials but in some cases they were preceded by brief negative potentials. Figure 1D shows such an example came from another+/fynz mouse. The early negative potentials (*) could be either antidromic action potentials in the mitral cells or passing fiber potentials of LOT or CF. When paired pulse stimulation with intervals of 30-100 ms were applied the late negative potentials consistently showed facilitation, while the early negative potentials were unchanged. This supports the view that the late negative potentials are excitatory postsynaptic potentials (EPSPs) originated from the granule cells.

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| FIG. 3.
Effect of (1S, 3R)-1-aminocyclo-pentane-1.3-dicarboxylate [(1S,3R)-ACPD] on fEPSP in +/fynz (+/ ) and fynz/fynz ( / ) mice. Superimposed traces are before application (C), 1 min after application (ACPD) and 5 min after wash out (W) of drug.
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Effects of antagonists of GABAA and glutamate receptors
It was reported that granule cells in the olfactory bulb receive GABAergic and glutamatergic synaptic inputs (Jahr and Nicoll 1982
; Mori and Kishi 1982
; Trombley and Westbrook 1990
; Wellis and Kauer 1994
). We investigated effects of antagonists of GABAA receptors and glutamate receptors on fEPSPs in the olfactory bulb slices. Figure 2 shows the sequence of maximum slopes of fEPSPs under the action of a series of antagonists. The maximal rate of rise of fEPSP was determined as described in METHODS. The maximal slope was measured within a time window selected around the rising phase of fEPSPs so as to exclude the presynaptic volleys (insets). In the slice of +/fynz mouse (Fig. 2A), application of bicuculline (25 µM) with picrotoxin (30 µM) greatly potentiated fEPSPs. After washing out the GABAA antagonist application of APV, an antagonist of N-methyl-D-aspartate (NMDA) receptor produced no appreciable change in fEPSPs, whereas CNQX, a nonNMDA antagonist almost completely blocked fEPSPs. The results indicate that fEPSPs are mainly generated by activation of non-NMDA receptors in the granule cells. In contrast to +/fynz mice, fynz/fynz mice were much less sensitive to GABAA antagonist, as shown in Fig. 2B. Application of bicuculline and picrotoxin in the same concentration as in +/fynz mice gave no potentiation of fEPSPs in fynz/fynz mice. APV was ineffective and CNQX suppressed fEPSPs in the same way as in +/fynz mice. The results suggest that GABAergic rather than glutamatergic transmission is disturbed in fynz/fynz mice. The average maximum slopes of fEPSPs after applying bicuculline and picrotoxin increased to 123.4 ± 3.1% in +/fynz mice (n = 12) but to 104 ± 4.7% in fynz/fynz mice (n = 9).

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| FIG. 4.
Effects of tetanic stimulation on fEPSP in olfactory bulb slices. A: comparison of fEPSP slopes before and after tetanic stimulation ( ). , data from +/fynz (+/ ) mice (7 slices, n = 7); , +/fynz mice in presence of APV (5 slices, n = 5); , data from fynz/fynz ( / ) mice (7 slices, n = 7). Each point represents average with SE. B-D: superimposed traces before and 15 min after tetanic stimulation in +/fynz mice (B), +/fynz mice in presence of APV (C), and in fynz/fynz ( / ) mice.
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We tested paired stimulation to the slices treated with bicuculline and picrotoxin. Paired pulse facilitation was consistently seen in the presence of GABAA antagonist both in +/fynz and fynz/fynz mice, indicating that the mechanism of paired pulse facilitation was not impaired in Fyn-deficient mice.
Effects of agonists of metabotropic glutamate receptors
We next examined the effects of agonists of metabotropic glutamate receptors on fEPSPs in the olfactory bulb, because the expression of metabotropic glutamate receptors (mGluR) have been documented (Hayashi et al. 1993
; Tromley and Westbrook 1990; Van Del Pol 1995
). Application of (1S,3R)-ACPD (100 µM) in +/fynz mice effectively suppressed fEPSPs (Fig. 3A). The peak amplitude of fEPSPs decreased to about 60% of the control but soon recovered after washing out the drug (5 slices, n = 5). Similar reversible suppression by (1S,3R)-ACPD was seen in fynz/fynz mice (7 slices, n = 7; Fig. 3B). By contrast, application of L-2-amino-4-phosphonobutyric (L-AP4;
100 µM) did not produce any appreciable change either in +/fynz (5 slices, n = 5) or fynz/fynz mice (2 slices,n = 2; data not shown). Because (1S,3R)-ACPD selectively activates mGluR 2,3 and L-AP4 activates mGluR 4,6,7, suppression of fEPSPs by (1S,3R)-ACPD could be caused by activation of mGluR 2 or mGluR 3 but not by mGluR 4,6,7. The results also indicate that mGluR 2 or mGluR 3 receptors in the olfactory bulb are not modified in Fyn-deficient mice.
Long-term potentiation in the olfactory bulb
When tetanic stimulation (2 trains of 100 pulses of 100 Hz) was applied to CF fibers, fEPSPs in +/fynz mice showed potentiation of fEPSPs. The magnitude of potentiation was 110-130% of the control and it lasted for more than 30 min, exhibiting a long-term potentiation (LTP; Fig. 4A). When we applied APV (100 µM) to the bathing solution, control low-frequency stimulation (0.08 Hz) gave no appreciable change in fEPSPs and the tetanic stimulation failed to elicit LTP (Fig. 4B). In contrast to the slices from +/fynz mice slices of fynz/fynz mice failed to show LTP of fEPSPs (Fig. 4C). Tetanic stimulation induced only transient potentiation and fEPSPs returned to the original level in 10 min. Profile of changes in the slope for fEPSPs after tetanus in fynz/fynz mice was similar to that in +/fynz mice treated with APV.

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| FIG. 5.
Schematic diagram of distributions of cells and possible synaptic connections in olfactory bulb. GL, glomerular layer; EPL, external plexiform layers; MCL, mitral cell layer; GCL, granule cell layer; ON, olfactory nerve; CF, centrifugal fibers; LOT, lateral olfactory tract; M/T, mitral/tufted cell; Gr, granule cell; Glu, glutamatergic synapse; GABA, GABAergic synapse.
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DISCUSSION |
Origin of field potentials in the olfactory bulb slice
In the present study, stimulation on the slice preparation could excite both afferent and efferent fibers of the olfactory bulb (Fig. 5). The afferents (CF), which consist of fibers from the piriform cortex, anterior olfactory nucleus, anterior commissure, and nucleus diagonal band make numerous synapses with the granule cells at various sites (Mori 1987
; Shepherd 1972
). The efferent fibers are axons of mitral/tufted (M/T) cells forming LOT. The antidromic activation of mitral cells may excite granule cells through the dendrodendritic and recurrent axon collateral synapses. We concluded that field potentials in the olfactory bulb originated from EPSPs in the granule cells for following reasons. First, paired pulse stimulation consistently produced facilitation of the negative field potentials, which are characteristic of the postsynaptic potentials with little contribution of antidromic responses. Second, it was reported that activation of the mitral cells by paired stimuli caused depression (paired pulse depression) of the granule cells through the reciprocal dendrodendritic synapses between the mitral cell and the granule cell (Jahr and Nicoll 1982
; Mori 1987
; Mori and Takagi 1978
). Third, (1S,3R)-ACPD, an agonist of mGluR2 inhibited fEPSPs both in +/fynz and fynz/fynz mice. By using the accessory olfactory bulb (AOB) of rat, Hayashi et al. (1993)
reported that mGluR2 activation could reduce GABA release from the granule cell to the mitral cell, which in turn could augment synaptic activation of the granule cells. Although AOB is different from the olfactory bulb in the present study, it is probable that inhibitory effect of (1S,3R)-ACPD could be caused by similar mechanism and dendrodendritic synapses contribute little, if any, in generation of fEPSPs. The field potentials in the olfactory bulb slice in the present study differed from in vivo experiments where LOT/CF stimulation generated both antidromic activation of M/T cells and orthodromic responses in granule cells (Mori 1987
; Nakashima et al. 1978
; Rall and Shepherd 1968
; Shepherd 1972
). Possibly, most of M/T cells are damaged in the process of taking out the olfactory bulb by cutting out the connecting olfactory nerves.
Because fEPSPs were not affected by APV but were nearly completely blocked by CNQX, they are mostly composed of
-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor-mediated response. Inhibition of granule cell responses by the glutamate receptor antagonists was reported in rat (Jacobson and Hamberger 1986) and in salamander (Wellis and Kauer 1994
) olfactory bulbs.
In fynz/fynz mice, the amplitude of fEPSPs was generally smaller than that in +/fynz mice. In a previous report on gross anatomy of fynz/fynz mice, no apparent abnormality was observed in the olfactory bulb by hematoxilin-eosin staining, although detailed histological study has not been done (Yagi et al. 1993b
). However, in 7-day-old pups of Fyn-deficient mutant, a reduced size of the modified glomerular complex (MGC) was observed (Yagi et al. 1993a
). One possible explanation for the smaller amplitude of fEPSPs in fynz/fynz mice is that deficiency of Fyn, which is essential for normal formation of the receptor molecules caused functional impairment during development in fynz/fynz mice.
Reduced sensitivity to GABAA receptor antagonists in Fyn-deficient mice
In +/fynz mice, fEPSPs were potentiated after applying bicuculline and picrotoxin indicating that GABAA receptors in the granule cells were blocked. In contrast, fEPSPs in fynz/fynz mice were much less sensitive to antagonists of GABAA receptors. The granule cells are known to receive inhibitory inputs from neighboring granule cells and other interneurons (Mori 1987
; Shepherd 1972
; Wellis and Kauer 1994
). Therefore the reduced sensitivity of fEPSPs in fynz/fynz mice to the antagonists could be caused by a reduction in the number of GABAA receptors in the granule cells. Alternatively, the mutual inhibitory transmission between the granule cells or GABAergic transmission from the short axon cells may be dysfunctional. Similar paired pulse facilitation of fEPSPs was seen in both +/fynz and fynz/fynz mice and this facilitation was not modified by GABAA antagonists. This suggests that the mechanism of facilitation was not impaired in Fyn-deficient mice.
Long-term potentiation in the olfactory bulb slice
So far, LTP in the olfactory system was reported by Stripling and colleagues (Patneau and Stripling 1992
; Stripling et al. 1991
) in in vivo study by using chronically implanted electrodes. They suggested that LTP may represent an enhancement of inhibitory interactions with the piriform cortex and between cortex and the olfactory bulb. In the slice of rat piriform cortex, Kanter and Haberly (1990)
found that LTP in the piriform cortex was blocked by APV, indicating that it is NMDA dependent. In the present study, LTP of fEPSPs in the granule cells of the olfactory bulb was foundto be NMDA receptor-dependent. Because APV did not affect fEPSPs with low-frequency stimulation, but blockedLTP, induction of LTP in the granule cells is triggered by activation of the NMDA receptor as in many other systems (Bliss and Collingridge 1993
). In relation to the function of NMDA receptors of Fyn-deficient mice, Miyakawa et al. (1997)
found that fynz/fynz mice were more sensitive to ethanol when measuring the duration of the loss of the righting reflex and they observed loss of acute tolerance to ethanol inhibition of NMDA-mediated EPSPs in CA1 pyramidal neurons in fynz/fynz mice.
 |
ACKNOWLEDGEMENTS |
We thank Dr. H.P.C. Robinson for valuable discussion and K. Matsumoto for technical assistance.
This work was supported by Japanese Ministry of Education, Science and Culture to N. Kawai, H. Niki, and T. Yagi.
 |
FOOTNOTES |
Address for reprint requests: N. Kawai, Dept. of Physiology, Jichi Medical School, Minamikawachi-machi, Tochigi-ken 329-04, Japan.
Received 13 March 1997; accepted in final form 24 September 1997.
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REFERENCES |
-
BLISS, T.V.P.,
COLLINGRIDGE, G. L. A
synaptic model of memory: long-term potentiation in the hippocampus.
Nature
361: 31-39, 1993.[Medline]
-
GRANT, S. N.,
O'DELL, T. J.,
KARL, K. A.,
STEIN, P. L.,
SORIANO, P.,
KANDEL, E. R.
Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice.
Science
258: 1903-1910, 1992.[Medline]
-
HAYASHI, Y.,
MOMIYAMA, A.,
TAKAHASHI, T.,
OHISHI, H.,
OGAWAMEGURO, R.,
SHIGEMOTO, R.,
MIZUNO, N.,
NAKANISHI, S.
Role of a metabotropic glutamate receptor in synaptic modulation in the accessory olfactory bulb.
Nature
366: 687-690, 1993.[Medline]
-
JACKOBSON, I.,
HAMBERGER, A.
Effects of kynurenic acid on evoked extracellular field potentials in the rat olfactory bulb in vivo.
Brain Res.
386: 389-392, 1986.[Medline]
-
JAHR, C. E.,
NICOLL, R. A.
An intracellular analysis of dendrodendritic inhibition in the turtle in vitro olfactory bulb.
J. Physiol. (Lond.)
326: 213-234, 1982.[Medline]
-
KANTER, E. D.,
HABERLY, L. B.
NMDA-dependent induction of long-term potentiation in afferent and association fiber systems of piriform cortex in vitro.
Brain Res.
525: 175-179, 1990.[Medline]
-
MIYAKAWA, T.,
YAGI, T.,
KITAZAWA, H.,
YASUDA, M.,
KAWAI, N.,
TSUBOI, K.,
NIKI, H.
Fyn-kinase as a determinant of ethanol sensitivity: relation to NMDA receptor function.
Science
278: 698-701, 1997.[Abstract/Free Full Text]
-
MIYAKAWA, T.,
YAGI, T.,
TANIGUCHI, M.,
MATSUURA, H.,
TATEISHI, K.,
NIKI, H.
Enhanced susceptibility of audiogenic seizures in Fyn-kinase deficient mice.
Mol. Brain Res.
28: 349-352, 1995. [Medline]
-
MIYAKAWA, T.,
YAGI, T.,
WATANABE, S.,
NIKI, H.
Increased fearfulness of Fyn tyrosine kinase deficient mice.
Mol. Brain Res.
27: 179-182, 1994. [Medline]
-
MORI, K.
Membrane and synaptic properties of identified neurons in the olfactory bulb.
Prog. Neurobiol.
29: 275-320, 1987.[Medline]
-
MORI, K.,
KISHI, K.
The morphology and physiology of the granule cells in the rabbit olfactory bulb revealed by intracellular recording and HRP injection.
Brain Res
247: 129-133, 1982.[Medline]
-
MORI, K.,
TAKAGI, S. F.
An intracellular study of dendrodendritic inhibitory synapses on mitral cells in the rabbit olfactory bulb.
J. Physiol. (Lond.)
279: 569-588, 1978.[Abstract]
-
NAKASHIMA, M.,
MORI, K.,
TAKAGI, S. F.
Centrifugal influence on olfactory bulb activity in the rabbit.
Brain Res.
154: 301-316, 1978.[Medline]
-
PATNEAU, D. K.,
STRIPLING, J. S.
Functional correlates of selective long-term potentiation inthe olfactory cortex and olfactory bulb.
Brain Res.
585: 210-228, 1992.
-
RALL, W.,
SHEPHERD, G. M.
Theoretical reconstruction of field potentials and dendrodendritic synaptic interactions in olfactory bulb.
J. Neurohysiol.
31: 884-915, 1968.[Free Full Text]
-
SHEPHERD, G. M.
Synaptic organization of the mammalian olfactory bulb.
Physiol. Rev.
52: 864-917, 1972.[Free Full Text]
-
STRIPLING, J. S.,
PATNEAU, D. K.,
GRAMLICH, C. A.
Characterization and anatomical distribution of selective long-term potntiation in the olfactory forebrain.
Brain Res.
542: 107-122, 1991.[Medline]
-
TROMBLEY, P. Q.,
WESTBROOK, G. L.
Excitatory synaptic transmission in cultures of rat olfactory bulb.
J. Neurophysiol.
64: 598-606, 1990.[Abstract/Free Full Text]
-
TROMBLEY, P. Q.,
WESTBROOK, G. L.
L-AP4 inhibits calcium currents and synaptic transmission via a G-protein-coupled glutamate receptor.
J. Neurosci.
12: 2043-2050, 1992.[Abstract]
-
TSUBOKAWA, H.,
OGURO, K.,
MASUZAWA, T.,
KAWAI, N.
Ca2+-dependent non-NMDA receptor-mediated synaptic currents in ischemic CA1 hippocampal neurons.
J. Neurophysiol.
71: 1190-1196, 1994.[Abstract]
-
TSUBOKAWA, H.,
OGURO, K.,
MASUZAWA, T.,
NAKAJIMA, T.,
KAWAI, N.
Effects of spider toxin and its analog on glutamate-activated currents in the hippocampal CA1 neuron after ischemia.
J. Neurophysiol.
74: 218-225, 1995.[Abstract/Free Full Text]
-
TSUBOKAWA, H.,
OGURO, K.,
ROBINSDON, H.P.C.,
MASUZAWA, T.,
KAWAI, N.
Intracellular inositol 1,3,4,5-tetrakisphosphate enhances the calcium current in hippocampal CA1 neurones of the gerbil following transient forebrain ischaemia.
J. Physiol. (Lond.)
497: 67-78, 1996.[Abstract]
-
VAN DEL POL, A. N.
Presynaptic metabotropic glutamate receptors in adult and developing neurons: autoexcitation in the olfactory bulb.
J. Comp. Biol.
359: 253-271, 1995.
-
WELLIS, D. P.,
KAUER, J. S.
GABAergic and glutamataergic synaptic input to identified granule cells in salamandar olfactory bulb.
J. Physiol. (Lond.)
475: 419-430, 1994.[Abstract]
-
YAGI, T.,
AIZAWA, S.,
TOKUNAGA, T.,
SHIGETANI, Y.,
TAKEDA, N.,
IKAWA, Y. A
role for Fyn tyrosine kinase in the suckling behaviour of neonatal mice.
Nature
366: 742-745, 1993a.[Medline]
-
YAGI, T.,
SHIGETANI, Y.,
OKADO, N.,
TOKUNAGA, T.,
IKAWA, Y.,
AIZAWA, S.
Regional localization of Fyn in adult brain; studies with mice in which fyn gene was replaced by lacZ.
Oncogene
8: 3343-3351, 1993b.[Medline]
-
YAGI, T.,
SHIGETANI, Y.,
FURUTA, Y.,
NADA, S.,
OKADO, N.,
IKAWA, Y.,
AIZAWA, S.
Fyn expression during early neurogenesis in mouse embryos.
Oncogene
1994: 2433-2440, 1994.