Riekki R, Pavlov I, Tornberg J, Lauri SE, Airaksinen MS, Taira T. Altered synaptic dynamics and h... more Riekki R, Pavlov I, Tornberg J, Lauri SE, Airaksinen MS, Taira T. Altered synaptic dynamics and hippocampal excitability but normal long-term plasticity in mice lacking hyperpolarizing GABA A receptor-mediated inhibition in CA1 pyramidal neurons. (GABA-AR)-mediated inhibition is critical for proper operation of neuronal networks. Synaptic inhibition either shifts the membrane potential farther away from the action potential firing threshold (hyperpolarizing inhibition) or via increase in the membrane conductance shunts the excitatory currents. However, the relative importance of these different forms of inhibition on the hippocampal function is unclear. To study the functional consequences of the absence of hyperpolarizing inhibition, we have used KCC2-deficient mice (KCC2 hy/null ) maintaining only 15-20% of the neuron-specific K-Cl-cotransporter. Gramicidin-perforated patchclamp recordings in hippocampal CA1 pyramidal cells revealed that the reversal potential of the GABA-AR-mediated postsynaptic currents (E GABA-A ) was ϳ20 mV more positive in KCC2 hy/null mice than in wild-type (WT) animals. The basic glutamatergic transmission appeared unaltered in the KCC2 hy/null mice, yet they displayed lowered threshold for stimulation-induced synchronous afterdischarges in the CA1 area. Also fatigue of field excitatory postsynaptic potentials/ excitatory postsynaptic currents in response to repetitious stimulation was smaller in KCC2 hy/null mice, indicating altered synaptic dynamics. Interestingly, this effect was present also under blockade of GABA-ARs and was dependent on the extracellular K ϩ concentration. Moreover, there were no differences in the levels of either long-term potentiation or long-term depression between the genotypes. The local hippocampal CA1 network can in several aspects maintain its functional viability even in the absence of hyperpolarizing inhibition in pyramidal cells. Our results underscore the central role of shunting type of inhibition in controlling the neuronal excitation/inhibition balance. Moreover, our data demonstrate a novel, unexpected role for the KCC2, namely the modulation of properties of glutamatergic transmission during repetitious afferent activity.
is an extracellular matrix-associated protein with neurite outgrowth-promoting activity and which... more is an extracellular matrix-associated protein with neurite outgrowth-promoting activity and which is suggested to be implicated in hippocampal synaptic plasticity. To study the functions of HB-GAM in adult brain we have produced HB-GAM overexpressing mice and compared phenotypic changes in the transgenic mice to those in the HB-GAM null mice. Both mutants were viable and displayed no gross morphological abnormalities. The basal synaptic transmission was normal in the area CA1 of hippocampal slices from the genetically modified mice. However, longterm potentiation (LTP) was attenuated in the mice overexpressing HB-GAM, whereas enhanced LTP was detected in the HB-GAM-deficient mice. Changes in LTP seen in vitro were paralleled by behavioral alterations in vivo. The animals overexpressing HB-GAM displayed faster learning in water maze and decreased anxiety in elevated plus-maze, while the HB-GAM knockouts demonstrated an opposite behavioral phenotype. These results show that HB-GAM suppresses LTP in hippocampus and plays a role in regulation of learning-related behavior.
sulfate proteoglycan expressed predominantly in the nervous system in a developmentally regulated... more sulfate proteoglycan expressed predominantly in the nervous system in a developmentally regulated manner. Syndecan-3 has been suggested to play a role in the development and plasticity of neuronal connections by linking extracellular signals to the regulation of the cytoskeleton. To study its physiological functions, we produced mice deficient in syndecan-3 by gene targeting. The mutant animals are healthy, are fertile, and have no apparent defects in the structure of the brain. We focused on characterizing the functions of the hippocampus, a brain area where expression of syndecan-3 is prominent in adults. Mice lacking syndecan-3 exhibited an enhanced level of long-term potentiation (LTP) in area CA1, while basal synaptic transmission and short-term plasticity were similar to those in wild-type animals. Further, the mutant mice were not responsive to the syndecan-3 ligand heparinbinding growth-associated molecule, which inhibits LTP in area CA1 in wild-type animals. Behavioral testing of the syndecan-3-deficient mice revealed impaired performance in tasks assessing hippocampal functioning. We suggest that syndecan-3 acts as an important modulator of synaptic plasticity that influences hippocampus-dependent memory.
During development neuronal circuitries are refined by activity. Here we studied the role of spon... more During development neuronal circuitries are refined by activity. Here we studied the role of spontaneous electrical activity in the regulation of synapse formation in the intact newborn (Postnatal Day 3; P3) rat hippocampus in vitro. The blockade of the spontaneous network activity with TTX led to an increase in the number of functional excitatory synapses in the CA3 area of the developing hippocampus. In parallel, there was a substantial increase in the expression levels of the presynaptic markers synaptophysin, synaptotagmin, and synapsin I and of GluR1 AMPA receptor subunits. These changes were associated with an increase in the frequency and amplitude of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs). Our correlated immunocytochemical, electronmicroscopical, and electrophysiological experiments indicate that in the developing hippocampus spontaneous network activity controls the number of functional synapses.
In this study, we have tried to understand why the left ventricle (LV) is not a homogeneous spher... more In this study, we have tried to understand why the left ventricle (LV) is not a homogeneous sphere. An experimental model of a spherical ventricle was developed. The chamber was configured as a mathematical model, and the wall properties were represented by isolated cardiac muscles. The stroke work of the spherical LV when modelling different types of inhomogeneity in the wall structure was investigated. It was found that the emergence of even slight inhomogeneity in a spherical ventricle inevitably results in a diminution of pump function. It was concluded that at a given level of the myocardial contractility, a homogeneous spherical LV would not have any functional reserve, ie no ability to maintain pump function in case of additional load. Functional reserve can be achieved only with a certain degree of inhomogeneity. Thus, inhomogeneity in the normal left ventricular wall structure constitutes a strategic functional reserve that is absent in a homogeneous spherical ventricle.
Research on event-related potential (ERP) correlates of auditory deviance-detection in newborns p... more Research on event-related potential (ERP) correlates of auditory deviance-detection in newborns provided inconsistent results; temporal and topographic ERP characteristics differed widely across studies and individual infants. Robust and reliable ERP responses were, however, obtained to sounds (termed ‘novel’ sounds), which cover a wide range of frequencies and widely differ from the context provided by a repeating sound [Kushnerenko et al., (2002) NeuroReport, 13, 1843–1848]. The question we investigated here is whether this effect can be attributed to novelty per se or to acoustic characteristics of the ‘novel’ sounds, such as their wide frequency spectrum and high signal energy compared with the repeated tones. We also asked how sensitivity to these stimulus aspects changes with development. Twelve newborns and 11 adults were tested in four different oddball conditions, each including a ‘standard’ sound presented with the probability of 0.8 and two types of infrequent ‘deviant’ sounds (0.1 probability, each). Deviants were (i) ‘novel’ sounds (diverse environmental noises); (ii) white-noise segments, or harmonic tones of (iii) a higher pitch, or (iv) higher intensity. In newborns, white-noise deviants elicited the largest response in all latency ranges, whereas in adults, this phenomenon was not found. Thus, newborns appear to be especially sensitive to sounds having a wide frequency spectrum. On the other hand, the pattern of results found for the late discriminative ERP response indicates that newborns may also be able to detect novelty in acoustic stimulation, although with a longer latency than adults, as shown by the ERP response. Results are discussed in terms of developmental refinement of the initially broadly tuned neonate auditory system.
Research on event-related potential (ERP) correlates of auditory deviance-detection in newborns p... more Research on event-related potential (ERP) correlates of auditory deviance-detection in newborns provided inconsistent results; temporal and topographic ERP characteristics differed widely across studies and individual infants. Robust and reliable ERP responses were, however, obtained to sounds (termed 'novel' sounds), which cover a wide range of frequencies and widely differ from the context provided by a repeating sound ) NeuroReport, 13, 1843-1848. The question we investigated here is whether this effect can be attributed to novelty per se or to acoustic characteristics of the 'novel' sounds, such as their wide frequency spectrum and high signal energy compared with the repeated tones. We also asked how sensitivity to these stimulus aspects changes with development. Twelve newborns and 11 adults were tested in four different oddball conditions, each including a 'standard' sound presented with the probability of 0.8 and two types of infrequent 'deviant' sounds (0.1 probability, each). Deviants were (i) 'novel' sounds (diverse environmental noises); (ii) white-noise segments, or harmonic tones of (iii) a higher pitch, or (iv) higher intensity. In newborns, white-noise deviants elicited the largest response in all latency ranges, whereas in adults, this phenomenon was not found. Thus, newborns appear to be especially sensitive to sounds having a wide frequency spectrum. On the other hand, the pattern of results found for the late discriminative ERP response indicates that newborns may also be able to detect novelty in acoustic stimulation, although with a longer latency than adults, as shown by the ERP response. Results are discussed in terms of developmental refinement of the initially broadly tuned neonate auditory system.
История века делается у нас на глазах. Мы с изумлением взираем на странные громады, выросшие на н... more История века делается у нас на глазах. Мы с изумлением взираем на странные громады, выросшие на недавних пустырях, а затем быстро к ним привыкаем, обживаем их и спешим дальше, к новым стоэтажным небоскребам.
Riekki R, Pavlov I, Tornberg J, Lauri SE, Airaksinen MS, Taira T. Altered synaptic dynamics and h... more Riekki R, Pavlov I, Tornberg J, Lauri SE, Airaksinen MS, Taira T. Altered synaptic dynamics and hippocampal excitability but normal long-term plasticity in mice lacking hyperpolarizing GABA A receptor-mediated inhibition in CA1 pyramidal neurons. (GABA-AR)-mediated inhibition is critical for proper operation of neuronal networks. Synaptic inhibition either shifts the membrane potential farther away from the action potential firing threshold (hyperpolarizing inhibition) or via increase in the membrane conductance shunts the excitatory currents. However, the relative importance of these different forms of inhibition on the hippocampal function is unclear. To study the functional consequences of the absence of hyperpolarizing inhibition, we have used KCC2-deficient mice (KCC2 hy/null ) maintaining only 15-20% of the neuron-specific K-Cl-cotransporter. Gramicidin-perforated patchclamp recordings in hippocampal CA1 pyramidal cells revealed that the reversal potential of the GABA-AR-mediated postsynaptic currents (E GABA-A ) was ϳ20 mV more positive in KCC2 hy/null mice than in wild-type (WT) animals. The basic glutamatergic transmission appeared unaltered in the KCC2 hy/null mice, yet they displayed lowered threshold for stimulation-induced synchronous afterdischarges in the CA1 area. Also fatigue of field excitatory postsynaptic potentials/ excitatory postsynaptic currents in response to repetitious stimulation was smaller in KCC2 hy/null mice, indicating altered synaptic dynamics. Interestingly, this effect was present also under blockade of GABA-ARs and was dependent on the extracellular K ϩ concentration. Moreover, there were no differences in the levels of either long-term potentiation or long-term depression between the genotypes. The local hippocampal CA1 network can in several aspects maintain its functional viability even in the absence of hyperpolarizing inhibition in pyramidal cells. Our results underscore the central role of shunting type of inhibition in controlling the neuronal excitation/inhibition balance. Moreover, our data demonstrate a novel, unexpected role for the KCC2, namely the modulation of properties of glutamatergic transmission during repetitious afferent activity.
is an extracellular matrix-associated protein with neurite outgrowth-promoting activity and which... more is an extracellular matrix-associated protein with neurite outgrowth-promoting activity and which is suggested to be implicated in hippocampal synaptic plasticity. To study the functions of HB-GAM in adult brain we have produced HB-GAM overexpressing mice and compared phenotypic changes in the transgenic mice to those in the HB-GAM null mice. Both mutants were viable and displayed no gross morphological abnormalities. The basal synaptic transmission was normal in the area CA1 of hippocampal slices from the genetically modified mice. However, longterm potentiation (LTP) was attenuated in the mice overexpressing HB-GAM, whereas enhanced LTP was detected in the HB-GAM-deficient mice. Changes in LTP seen in vitro were paralleled by behavioral alterations in vivo. The animals overexpressing HB-GAM displayed faster learning in water maze and decreased anxiety in elevated plus-maze, while the HB-GAM knockouts demonstrated an opposite behavioral phenotype. These results show that HB-GAM suppresses LTP in hippocampus and plays a role in regulation of learning-related behavior.
sulfate proteoglycan expressed predominantly in the nervous system in a developmentally regulated... more sulfate proteoglycan expressed predominantly in the nervous system in a developmentally regulated manner. Syndecan-3 has been suggested to play a role in the development and plasticity of neuronal connections by linking extracellular signals to the regulation of the cytoskeleton. To study its physiological functions, we produced mice deficient in syndecan-3 by gene targeting. The mutant animals are healthy, are fertile, and have no apparent defects in the structure of the brain. We focused on characterizing the functions of the hippocampus, a brain area where expression of syndecan-3 is prominent in adults. Mice lacking syndecan-3 exhibited an enhanced level of long-term potentiation (LTP) in area CA1, while basal synaptic transmission and short-term plasticity were similar to those in wild-type animals. Further, the mutant mice were not responsive to the syndecan-3 ligand heparinbinding growth-associated molecule, which inhibits LTP in area CA1 in wild-type animals. Behavioral testing of the syndecan-3-deficient mice revealed impaired performance in tasks assessing hippocampal functioning. We suggest that syndecan-3 acts as an important modulator of synaptic plasticity that influences hippocampus-dependent memory.
During development neuronal circuitries are refined by activity. Here we studied the role of spon... more During development neuronal circuitries are refined by activity. Here we studied the role of spontaneous electrical activity in the regulation of synapse formation in the intact newborn (Postnatal Day 3; P3) rat hippocampus in vitro. The blockade of the spontaneous network activity with TTX led to an increase in the number of functional excitatory synapses in the CA3 area of the developing hippocampus. In parallel, there was a substantial increase in the expression levels of the presynaptic markers synaptophysin, synaptotagmin, and synapsin I and of GluR1 AMPA receptor subunits. These changes were associated with an increase in the frequency and amplitude of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs). Our correlated immunocytochemical, electronmicroscopical, and electrophysiological experiments indicate that in the developing hippocampus spontaneous network activity controls the number of functional synapses.
In this study, we have tried to understand why the left ventricle (LV) is not a homogeneous spher... more In this study, we have tried to understand why the left ventricle (LV) is not a homogeneous sphere. An experimental model of a spherical ventricle was developed. The chamber was configured as a mathematical model, and the wall properties were represented by isolated cardiac muscles. The stroke work of the spherical LV when modelling different types of inhomogeneity in the wall structure was investigated. It was found that the emergence of even slight inhomogeneity in a spherical ventricle inevitably results in a diminution of pump function. It was concluded that at a given level of the myocardial contractility, a homogeneous spherical LV would not have any functional reserve, ie no ability to maintain pump function in case of additional load. Functional reserve can be achieved only with a certain degree of inhomogeneity. Thus, inhomogeneity in the normal left ventricular wall structure constitutes a strategic functional reserve that is absent in a homogeneous spherical ventricle.
Research on event-related potential (ERP) correlates of auditory deviance-detection in newborns p... more Research on event-related potential (ERP) correlates of auditory deviance-detection in newborns provided inconsistent results; temporal and topographic ERP characteristics differed widely across studies and individual infants. Robust and reliable ERP responses were, however, obtained to sounds (termed ‘novel’ sounds), which cover a wide range of frequencies and widely differ from the context provided by a repeating sound [Kushnerenko et al., (2002) NeuroReport, 13, 1843–1848]. The question we investigated here is whether this effect can be attributed to novelty per se or to acoustic characteristics of the ‘novel’ sounds, such as their wide frequency spectrum and high signal energy compared with the repeated tones. We also asked how sensitivity to these stimulus aspects changes with development. Twelve newborns and 11 adults were tested in four different oddball conditions, each including a ‘standard’ sound presented with the probability of 0.8 and two types of infrequent ‘deviant’ sounds (0.1 probability, each). Deviants were (i) ‘novel’ sounds (diverse environmental noises); (ii) white-noise segments, or harmonic tones of (iii) a higher pitch, or (iv) higher intensity. In newborns, white-noise deviants elicited the largest response in all latency ranges, whereas in adults, this phenomenon was not found. Thus, newborns appear to be especially sensitive to sounds having a wide frequency spectrum. On the other hand, the pattern of results found for the late discriminative ERP response indicates that newborns may also be able to detect novelty in acoustic stimulation, although with a longer latency than adults, as shown by the ERP response. Results are discussed in terms of developmental refinement of the initially broadly tuned neonate auditory system.
Research on event-related potential (ERP) correlates of auditory deviance-detection in newborns p... more Research on event-related potential (ERP) correlates of auditory deviance-detection in newborns provided inconsistent results; temporal and topographic ERP characteristics differed widely across studies and individual infants. Robust and reliable ERP responses were, however, obtained to sounds (termed 'novel' sounds), which cover a wide range of frequencies and widely differ from the context provided by a repeating sound ) NeuroReport, 13, 1843-1848. The question we investigated here is whether this effect can be attributed to novelty per se or to acoustic characteristics of the 'novel' sounds, such as their wide frequency spectrum and high signal energy compared with the repeated tones. We also asked how sensitivity to these stimulus aspects changes with development. Twelve newborns and 11 adults were tested in four different oddball conditions, each including a 'standard' sound presented with the probability of 0.8 and two types of infrequent 'deviant' sounds (0.1 probability, each). Deviants were (i) 'novel' sounds (diverse environmental noises); (ii) white-noise segments, or harmonic tones of (iii) a higher pitch, or (iv) higher intensity. In newborns, white-noise deviants elicited the largest response in all latency ranges, whereas in adults, this phenomenon was not found. Thus, newborns appear to be especially sensitive to sounds having a wide frequency spectrum. On the other hand, the pattern of results found for the late discriminative ERP response indicates that newborns may also be able to detect novelty in acoustic stimulation, although with a longer latency than adults, as shown by the ERP response. Results are discussed in terms of developmental refinement of the initially broadly tuned neonate auditory system.
История века делается у нас на глазах. Мы с изумлением взираем на странные громады, выросшие на н... more История века делается у нас на глазах. Мы с изумлением взираем на странные громады, выросшие на недавних пустырях, а затем быстро к ним привыкаем, обживаем их и спешим дальше, к новым стоэтажным небоскребам.
Uploads
Papers by ivan pavlov