Effects of internal Sr 2 ϩ on the activity of large-conductance Ca 2 ϩ -activated K ϩ channels we... more Effects of internal Sr 2 ϩ on the activity of large-conductance Ca 2 ϩ -activated K ϩ channels were studied in inside-out membrane patches from goldfish saccular hair cells. Sr 2 ϩ was approximately one-fourth as potent as Ca 2 ϩ in activating these channels. Although the Hill coefficient for Sr 2 ϩ was smaller than that for Ca 2 ϩ , maximum open-state probability, voltage dependence, steady state gating kinetics, and time courses of activation and deactivation of the channel were very similar under the presence of equipotent concentrations of Ca 2 ϩ and Sr 2 ϩ . This suggests that voltage-dependent activation is partially independent of the ligand. Internal Sr 2 ϩ at higher concentrations ( Ͼ 100 M) produced fast and slow blockade both concentration and voltage dependently. The reduction in single-channel amplitude (fast blockade) could be fitted with a modified Woodhull equation that incorporated the Hill coefficient. The dissociation constant at 0 mV, the Hill coefficient, and zd (a product of the charge of the blocking ion and the fraction of the voltage difference at the binding site from the inside) in this equation were 58-209 mM, 0.69-0.75, 0.45-0.51, respectively ( n ϭ 4). Long shut events (slow blockade) produced by Sr 2 ϩ lasted ف 10-200 ms and could be fitted with single-exponential curves (time constant, l Ϫ s ) in shut-time histograms. Durations of burst events, periods intercalated by long shut events, could also be fitted with single exponentials (time constant, b ). A significant decrease in b and no large changes in l Ϫ s were observed with increased Sr 2 ϩ concentration and voltage. These findings on slow blockade could be approximated by a model in which single Sr 2 ϩ ions bind to a blocking site within the channel pore beyond the energy barrier from the inside, as proposed for Ba 2 ϩ blockade. The dissociation constant at 0 mV and zd in the Woodhull equation for this model were 36-150 mM and 1-1.8, respectively ( n ϭ 3).
The Journal of Neuroscience the Official Journal of the Society For Neuroscience, May 15, 2000
Elimination of cerebellar granule cells early during postnatal development produces abnormal neur... more Elimination of cerebellar granule cells early during postnatal development produces abnormal neural organization that retains immature characteristics in the adult, including innervation of each Purkinje cell by multiple climbing fibers from the inferior olive. To elucidate mechanisms underlying development of the olivocerebellar projection, we studied light-microscopic morphology of single olivocerebellar axons labeled with biotinylated dextran amine in adult rats rendered agranular by a single postnatal X-irradiation.
The cerebellar cortex is compartmentalized into more than 20 longitudinal stripes by the aldolase... more The cerebellar cortex is compartmentalized into more than 20 longitudinal stripes by the aldolase C (=zebrin) expression pattern, which is tightly correlated with the topography of the olivocortical climbing fiber projection. Here we labeled Purkinje cells in different aldolase C stripes of the cerebellar cortex with biotinylated dextran amine and analyzed their axonal trajectories to clarify the compartmentalization of the cerebellar nuclei in the rat. Each Purkinje cell axon had a relatively small termination area in the cerebellar nucleus, which were often elongated from the surface toward the hilus of the nucleus. The axonal projection seemed to be organized according to fine cortico-nuclear topography. Purkinje cells in the aldolase C-positive and negative stripes in the cortex projected to the caudoventral and rostrodorsal parts of the nuclei, respectively. These results supported that the aldolase C expression is tightly related with the functional cortico-nuclear organization.
Neuronal activity in the putamen of monkeys was recorded during sequential performance of multipl... more Neuronal activity in the putamen of monkeys was recorded during sequential performance of multiple movements.
The functional partitioning of the cerebellar cortex depends on the projection patterns of its af... more The functional partitioning of the cerebellar cortex depends on the projection patterns of its afferent and efferent neurons. However, the entire morphology of individual projection neurons has been demonstrated in only a few classes of neurons in the vertebrate CNS. To investigate the contribution of the projection pattern of individual olivocerebellar axons to the cerebellar functional compartmentalization, we labeled individual olivocerebellar axons, which terminate in the cerebellar cortex as climbing fibers, with biotinylated dextran amine injected into the inferior olive in the rat, and completely reconstructed the entire trajectories of 34 olivocerebellar axons from serial sections of the cerebellum and medulla. Single axons had seven climbing fibers on average, which terminated at similar distances from the midline in a single or in multiple lobules. Cortical projection areas of adjacent olivary neurons were clustered as narrow but separate longitudinal segments and often innervated by collaterals of single neurons. Comparison of the cerebellar distribution of olivocerebellar axons arising from different sites within a single olivary subnucleus indicated that slightly distant neurons projected to complementary sets of such segments in a single longitudinal band. Several of these longitudinal bands formed a so-called parasagittal zone innervated by a subnucleus of the inferior olive. Single olivocerebellar axons projected rostrocaudally to segments within a single band but did not project mediolaterally to multiple bands. These results suggest fine substructural organization in the cerebellar compartmentalization that may represent functional units.
For many decades, the predominant view in the cerebellar field has been that the olivocerebellar ... more For many decades, the predominant view in the cerebellar field has been that the olivocerebellar system's primary function is to induce plasticity in the cerebellar cortex, specifically, at the parallel fiber-Purkinje cell synapse. However, it has also long been proposed that the olivocerebellar system participates directly in motor control by helping to shape ongoing motor commands being issued by the cerebellum. Evidence consistent with both hypotheses exists; however, they are often investigated as mutually exclusive alternatives. In contrast, here, we take the perspective that the olivocerebellar system can contribute to both the motor learning and motor control functions of the cerebellum and might also play a role in development. We then consider the potential problems and benefits of it having multiple functions. Moreover, we discuss how its distinctive characteristics (e.g., low firing rates, synchronization, and variable complex spike waveforms) make it more or less sui...
Neuronal activity in the putamen of monkeys was recorded during sequential performance of multipl... more Neuronal activity in the putamen of monkeys was recorded during sequential performance of multiple movements.
In this study, we examined the decremental response in the hair cell-afferent fibre synapse of go... more In this study, we examined the decremental response in the hair cell-afferent fibre synapse of goldfish. This decremental response is a transient reduction in sound-evoked EPSPs associated with a step reduction in sound intensity. To determine its presynaptic correlates, a patch clamp study was performed on oscillatory-type hair cells isolated from the sacculus of goldfish. Injection of depolarizing current produced a damped oscillation in the membrane potential of such cells. When the current intensity was reduced in steps, instead of simply being turned off, very marked dips were produced as off-oscillation in the hair cell membrane potential. These dips correlated with the decremental response in EPSPs.
It has been suggested that maternal immune activation increases the risk of psychiatric disorders... more It has been suggested that maternal immune activation increases the risk of psychiatric disorders such as schizophrenia in offspring. There are many reports about hippocampal structural pathology in schizophrenia. Antipsychotic drug administration in adolescence prevented postpubertal hippocampal structural pathology in the maternal immune activation animal model. These findings suggest the possibility that maternal immune activation induces hippocampal dysfunction in juvenile offspring. To test this hypothesis, we investigated hippocampal function in juvenile offspring of maternal immune activation model rat. A synthetic double-stranded RNA polyriboinosinic-polyribocytidilic acid (Poly I:C; 4 mg/kg/day, I.P.) was injected to pregnant rats on gestation days 15 and 17, in order to cause immune activation by stimulating Toll-like receptor 3. Hippocampal synaptic function and morphology in their juvenile offspring (postnatal days 28-31) were compared to those in vehicle-injected control offspring. Field responses were recorded in the hippocampal CA1 region by stimulating commissural/Schaffer collaterals. Pre-synaptic fiber volley amplitudes (mV) and field excitatory post-synaptic potential slopes (mV/ms) were significantly lower in treated offspring. In addition, short-term synaptic plasticity, namely, the paired-pulse facilitation ratio, was significantly higher and long-term synaptic plasticity (long-term potentiation) was significantly impaired in treated offspring. Furthermore, major presynaptic protein (synaptophysin) expressions were decreased, but not major post-synaptic proteins (GluR1, GluR2/3, and NR1), in hippocampal CA1 of treated offspring, whereas Keywords: Schizophrenia Maternal immune activation Hippocampus Synapse Poly I:C Cytokine B R A I N R E S E A R C H 1 3 6 3 ( 2 0 1 0 ) 1 7 0 -1 7 9 ⁎ Corresponding author. Fax: + 81 43 253 0396. E-mail address: [email protected] (A. Oh-Nishi). a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m w w w . e l s e v i e r . c o m / l o c a t e / b r a i n r e s neuronal loss was not detected in the hippocampal CA1-CA3 regions. These results indicate that maternal immune activation leads to synaptic dysfunction without neuronal loss in the hippocampus of juvenile offspring, and this may be one of the early stages of schizophrenia pathologies.
1. Ionic currents underlying the oscillatory response of membrane potential were studied in oscil... more 1. Ionic currents underlying the oscillatory response of membrane potential were studied in oscillatory-type hair cells isolated from the goldfish sacculus with the whole-cell recording method using a patch pipette. 2. Bath application of 4-aminopyridine (4-AP; 10 mM) reversibly produced moderate depolarization of the resting potential along with complete suppression of the oscillatory response. Sustained injection of a small depolarizing current also suppressed the oscillatory response. 3. A 4-AP-sensitive atypical A-type K+ current which had a high threshold voltage for inactivation (IA(H)) was found to be a major outward current underlying the oscillatory response. 4. IA(H) was activated with a time constant of 0.4-10 ms and was inactivated slowly with a time constant of 0.6-2 s. IA(H) activation and inactivation occurred mostly at membrane potentials more positive than -70 mV. 5. There was a clear correlation between activation speed of IA(H) and the frequency of pulse-evoked oscillation. A 'hump'-type response was produced in about one-quarter of the oscillatory-type hair cells.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
The functional partitioning of the cerebellar cortex depends on the projection patterns of its af... more The functional partitioning of the cerebellar cortex depends on the projection patterns of its afferent and efferent neurons. However, the entire morphology of individual projection neurons has been demonstrated in only a few classes of neurons in the vertebrate CNS. To investigate the contribution of the projection pattern of individual olivocerebellar axons to the cerebellar functional compartmentalization, we labeled individual olivocerebellar axons, which terminate in the cerebellar cortex as climbing fibers, with biotinylated dextran amine injected into the inferior olive in the rat, and completely reconstructed the entire trajectories of 34 olivocerebellar axons from serial sections of the cerebellum and medulla. Single axons had seven climbing fibers on average, which terminated at similar distances from the midline in a single or in multiple lobules. Cortical projection areas of adjacent olivary neurons were clustered as narrow but separate longitudinal segments and often innervated by collaterals of single neurons. Comparison of the cerebellar distribution of olivocerebellar axons arising from different sites within a single olivary subnucleus indicated that slightly distant neurons projected to complementary sets of such segments in a single longitudinal band. Several of these longitudinal bands formed a so-called parasagittal zone innervated by a subnucleus of the inferior olive. Single olivocerebellar axons projected rostrocaudally to segments within a single band but did not project mediolaterally to multiple bands. These results suggest fine substructural organization in the cerebellar compartmentalization that may represent functional units.
Effects of internal Sr 2 ϩ on the activity of large-conductance Ca 2 ϩ -activated K ϩ channels we... more Effects of internal Sr 2 ϩ on the activity of large-conductance Ca 2 ϩ -activated K ϩ channels were studied in inside-out membrane patches from goldfish saccular hair cells. Sr 2 ϩ was approximately one-fourth as potent as Ca 2 ϩ in activating these channels. Although the Hill coefficient for Sr 2 ϩ was smaller than that for Ca 2 ϩ , maximum open-state probability, voltage dependence, steady state gating kinetics, and time courses of activation and deactivation of the channel were very similar under the presence of equipotent concentrations of Ca 2 ϩ and Sr 2 ϩ . This suggests that voltage-dependent activation is partially independent of the ligand. Internal Sr 2 ϩ at higher concentrations ( Ͼ 100 M) produced fast and slow blockade both concentration and voltage dependently. The reduction in single-channel amplitude (fast blockade) could be fitted with a modified Woodhull equation that incorporated the Hill coefficient. The dissociation constant at 0 mV, the Hill coefficient, and zd (a product of the charge of the blocking ion and the fraction of the voltage difference at the binding site from the inside) in this equation were 58-209 mM, 0.69-0.75, 0.45-0.51, respectively ( n ϭ 4). Long shut events (slow blockade) produced by Sr 2 ϩ lasted ف 10-200 ms and could be fitted with single-exponential curves (time constant, l Ϫ s ) in shut-time histograms. Durations of burst events, periods intercalated by long shut events, could also be fitted with single exponentials (time constant, b ). A significant decrease in b and no large changes in l Ϫ s were observed with increased Sr 2 ϩ concentration and voltage. These findings on slow blockade could be approximated by a model in which single Sr 2 ϩ ions bind to a blocking site within the channel pore beyond the energy barrier from the inside, as proposed for Ba 2 ϩ blockade. The dissociation constant at 0 mV and zd in the Woodhull equation for this model were 36-150 mM and 1-1.8, respectively ( n ϭ 3).
The Journal of Neuroscience the Official Journal of the Society For Neuroscience, May 15, 2000
Elimination of cerebellar granule cells early during postnatal development produces abnormal neur... more Elimination of cerebellar granule cells early during postnatal development produces abnormal neural organization that retains immature characteristics in the adult, including innervation of each Purkinje cell by multiple climbing fibers from the inferior olive. To elucidate mechanisms underlying development of the olivocerebellar projection, we studied light-microscopic morphology of single olivocerebellar axons labeled with biotinylated dextran amine in adult rats rendered agranular by a single postnatal X-irradiation.
The cerebellar cortex is compartmentalized into more than 20 longitudinal stripes by the aldolase... more The cerebellar cortex is compartmentalized into more than 20 longitudinal stripes by the aldolase C (=zebrin) expression pattern, which is tightly correlated with the topography of the olivocortical climbing fiber projection. Here we labeled Purkinje cells in different aldolase C stripes of the cerebellar cortex with biotinylated dextran amine and analyzed their axonal trajectories to clarify the compartmentalization of the cerebellar nuclei in the rat. Each Purkinje cell axon had a relatively small termination area in the cerebellar nucleus, which were often elongated from the surface toward the hilus of the nucleus. The axonal projection seemed to be organized according to fine cortico-nuclear topography. Purkinje cells in the aldolase C-positive and negative stripes in the cortex projected to the caudoventral and rostrodorsal parts of the nuclei, respectively. These results supported that the aldolase C expression is tightly related with the functional cortico-nuclear organization.
Neuronal activity in the putamen of monkeys was recorded during sequential performance of multipl... more Neuronal activity in the putamen of monkeys was recorded during sequential performance of multiple movements.
The functional partitioning of the cerebellar cortex depends on the projection patterns of its af... more The functional partitioning of the cerebellar cortex depends on the projection patterns of its afferent and efferent neurons. However, the entire morphology of individual projection neurons has been demonstrated in only a few classes of neurons in the vertebrate CNS. To investigate the contribution of the projection pattern of individual olivocerebellar axons to the cerebellar functional compartmentalization, we labeled individual olivocerebellar axons, which terminate in the cerebellar cortex as climbing fibers, with biotinylated dextran amine injected into the inferior olive in the rat, and completely reconstructed the entire trajectories of 34 olivocerebellar axons from serial sections of the cerebellum and medulla. Single axons had seven climbing fibers on average, which terminated at similar distances from the midline in a single or in multiple lobules. Cortical projection areas of adjacent olivary neurons were clustered as narrow but separate longitudinal segments and often innervated by collaterals of single neurons. Comparison of the cerebellar distribution of olivocerebellar axons arising from different sites within a single olivary subnucleus indicated that slightly distant neurons projected to complementary sets of such segments in a single longitudinal band. Several of these longitudinal bands formed a so-called parasagittal zone innervated by a subnucleus of the inferior olive. Single olivocerebellar axons projected rostrocaudally to segments within a single band but did not project mediolaterally to multiple bands. These results suggest fine substructural organization in the cerebellar compartmentalization that may represent functional units.
For many decades, the predominant view in the cerebellar field has been that the olivocerebellar ... more For many decades, the predominant view in the cerebellar field has been that the olivocerebellar system's primary function is to induce plasticity in the cerebellar cortex, specifically, at the parallel fiber-Purkinje cell synapse. However, it has also long been proposed that the olivocerebellar system participates directly in motor control by helping to shape ongoing motor commands being issued by the cerebellum. Evidence consistent with both hypotheses exists; however, they are often investigated as mutually exclusive alternatives. In contrast, here, we take the perspective that the olivocerebellar system can contribute to both the motor learning and motor control functions of the cerebellum and might also play a role in development. We then consider the potential problems and benefits of it having multiple functions. Moreover, we discuss how its distinctive characteristics (e.g., low firing rates, synchronization, and variable complex spike waveforms) make it more or less sui...
Neuronal activity in the putamen of monkeys was recorded during sequential performance of multipl... more Neuronal activity in the putamen of monkeys was recorded during sequential performance of multiple movements.
In this study, we examined the decremental response in the hair cell-afferent fibre synapse of go... more In this study, we examined the decremental response in the hair cell-afferent fibre synapse of goldfish. This decremental response is a transient reduction in sound-evoked EPSPs associated with a step reduction in sound intensity. To determine its presynaptic correlates, a patch clamp study was performed on oscillatory-type hair cells isolated from the sacculus of goldfish. Injection of depolarizing current produced a damped oscillation in the membrane potential of such cells. When the current intensity was reduced in steps, instead of simply being turned off, very marked dips were produced as off-oscillation in the hair cell membrane potential. These dips correlated with the decremental response in EPSPs.
It has been suggested that maternal immune activation increases the risk of psychiatric disorders... more It has been suggested that maternal immune activation increases the risk of psychiatric disorders such as schizophrenia in offspring. There are many reports about hippocampal structural pathology in schizophrenia. Antipsychotic drug administration in adolescence prevented postpubertal hippocampal structural pathology in the maternal immune activation animal model. These findings suggest the possibility that maternal immune activation induces hippocampal dysfunction in juvenile offspring. To test this hypothesis, we investigated hippocampal function in juvenile offspring of maternal immune activation model rat. A synthetic double-stranded RNA polyriboinosinic-polyribocytidilic acid (Poly I:C; 4 mg/kg/day, I.P.) was injected to pregnant rats on gestation days 15 and 17, in order to cause immune activation by stimulating Toll-like receptor 3. Hippocampal synaptic function and morphology in their juvenile offspring (postnatal days 28-31) were compared to those in vehicle-injected control offspring. Field responses were recorded in the hippocampal CA1 region by stimulating commissural/Schaffer collaterals. Pre-synaptic fiber volley amplitudes (mV) and field excitatory post-synaptic potential slopes (mV/ms) were significantly lower in treated offspring. In addition, short-term synaptic plasticity, namely, the paired-pulse facilitation ratio, was significantly higher and long-term synaptic plasticity (long-term potentiation) was significantly impaired in treated offspring. Furthermore, major presynaptic protein (synaptophysin) expressions were decreased, but not major post-synaptic proteins (GluR1, GluR2/3, and NR1), in hippocampal CA1 of treated offspring, whereas Keywords: Schizophrenia Maternal immune activation Hippocampus Synapse Poly I:C Cytokine B R A I N R E S E A R C H 1 3 6 3 ( 2 0 1 0 ) 1 7 0 -1 7 9 ⁎ Corresponding author. Fax: + 81 43 253 0396. E-mail address: [email protected] (A. Oh-Nishi). a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m w w w . e l s e v i e r . c o m / l o c a t e / b r a i n r e s neuronal loss was not detected in the hippocampal CA1-CA3 regions. These results indicate that maternal immune activation leads to synaptic dysfunction without neuronal loss in the hippocampus of juvenile offspring, and this may be one of the early stages of schizophrenia pathologies.
1. Ionic currents underlying the oscillatory response of membrane potential were studied in oscil... more 1. Ionic currents underlying the oscillatory response of membrane potential were studied in oscillatory-type hair cells isolated from the goldfish sacculus with the whole-cell recording method using a patch pipette. 2. Bath application of 4-aminopyridine (4-AP; 10 mM) reversibly produced moderate depolarization of the resting potential along with complete suppression of the oscillatory response. Sustained injection of a small depolarizing current also suppressed the oscillatory response. 3. A 4-AP-sensitive atypical A-type K+ current which had a high threshold voltage for inactivation (IA(H)) was found to be a major outward current underlying the oscillatory response. 4. IA(H) was activated with a time constant of 0.4-10 ms and was inactivated slowly with a time constant of 0.6-2 s. IA(H) activation and inactivation occurred mostly at membrane potentials more positive than -70 mV. 5. There was a clear correlation between activation speed of IA(H) and the frequency of pulse-evoked oscillation. A 'hump'-type response was produced in about one-quarter of the oscillatory-type hair cells.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
The functional partitioning of the cerebellar cortex depends on the projection patterns of its af... more The functional partitioning of the cerebellar cortex depends on the projection patterns of its afferent and efferent neurons. However, the entire morphology of individual projection neurons has been demonstrated in only a few classes of neurons in the vertebrate CNS. To investigate the contribution of the projection pattern of individual olivocerebellar axons to the cerebellar functional compartmentalization, we labeled individual olivocerebellar axons, which terminate in the cerebellar cortex as climbing fibers, with biotinylated dextran amine injected into the inferior olive in the rat, and completely reconstructed the entire trajectories of 34 olivocerebellar axons from serial sections of the cerebellum and medulla. Single axons had seven climbing fibers on average, which terminated at similar distances from the midline in a single or in multiple lobules. Cortical projection areas of adjacent olivary neurons were clustered as narrow but separate longitudinal segments and often innervated by collaterals of single neurons. Comparison of the cerebellar distribution of olivocerebellar axons arising from different sites within a single olivary subnucleus indicated that slightly distant neurons projected to complementary sets of such segments in a single longitudinal band. Several of these longitudinal bands formed a so-called parasagittal zone innervated by a subnucleus of the inferior olive. Single olivocerebellar axons projected rostrocaudally to segments within a single band but did not project mediolaterally to multiple bands. These results suggest fine substructural organization in the cerebellar compartmentalization that may represent functional units.
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Papers by Izumi Sugihara