- Email: [email protected]
Persistent synaptic plasticity in the hippocampocortical pathway reproduced in vitro
Abstracts / Neuroscience Research 68S (2010) e335–e446
e345
the impairment of learning and memory known to be caused by estrogen depletion.
the pathological rhythms and the difference can differentiate the memory process induced in the two rhythms.
doi:10.1016/j.neures.2010.07.1526
doi:10.1016/j.neures.2010.07.1528
P3-b13 Construction of CaMKII-interacting protein network obtained from affinity purified proteins in silico and its experimental verification
P3-b15 Age-dependent impairments of hippocampal synaptic plasticity and hippocampus-dependent learning in drebrin A-specific knockout mice
Takafumi Yamada 1 , Akihiro Iwamatsu 2 , Takeshi Obayashi 3 , Kengo Kinoshita 3 , Shunji Ohsako 1
Nobuhiko Kojima 1 , Hiroki Yasuda 2 , Kenji Hanamura 1 , Tomoaki Shirao 1
1
1 Department of Neurobiology & Behavior, Gunma University Graduate School of Medicine, Maebashi 2 Education & Research Support Center, Gunma University Graduate School of Medicine, Maebashi
Tokyo Metro Inst for Neurosci, Tokyo 2 Protein Research Network, Inc, Yokohama 3 Grad Sch of Info Sci, Tohoku Univ, Sendai
CaMKII is a key kinase which involves in neural plasticity through its structural function and enzymatic activity. Drosophila CaMKII possessing single gene limits a molecular complexity derived from the isoforms relative to mammalian CaMKII. We therefore constructed a molecular network applying CaMKII-interacting proteins identified from Drosophila melanogaster. Although most of which 74 candidates identified by peptide mass fingerprinting have not been known as the CaMKII-interacting proteins, 70% of these were postsynaptic density proteins or synaptic vesicle’s proteins identified from proteome analyses, suggesting that these proteins were related to synaptic plasticity. We applied our coexpression database(db) [COXPRES db; http://coxpresdb.jp] providing coexpressed gene lists and networks concomitantly with protein-protein interaction. Networks related with translation and nucleocytoplasmic transport were successfully extracted by application of their human orthologs. NMDA receptor (NR) subunits were found to intervene between CaMKII and the identified proteins on a network. C terminal cytoplasmic region (Ct) of NR subunits which interact with signaling and scaffold proteins is important for synaptic plasticity. dCaMKII binds both Cts of dNR1 and dNR2 in GST pull down assay. Interestingly the dNR2 sequence is much shorter than vertebrate NR2 without any similar sequences and the known binding site different from dNR1 sequence similar to vertebrate NR1. The successful construction of network by human orthologues of different species and feature of conserved binding mode in nonconserved domain of NR imply that a common system works in synaptic plasticity between Drosophila and human. We will discuss about conservation of functional network and structural differences among organisms especially in NRs.
Dendritic spines are postsynaptic structures at excitatory synapses that play important roles in synaptic function. Actin-based cytoskeletal networks in dendritic spines determine the dynamics of spine morphology. Drebrin A, a neuron-specific isoform of drebrin, is a component of actin cytoskeletal structure in spines and is thought to have a pivotal role in spine morphogenesis and plasticity. To understand the role of drebrin A in brain functions, we generated drebrin A-specific knockout (DAKO) mice by deleting the drebrin A-specific exon. In DAKO mice drebrin E, another isoform of drebrin, continued to be expressed in the adult brain instead of drebrin A. These mice are viable and reveal no gross abnormalities in the brain. We have recently reported that DAKO mice showed impairment of contextual fear learning, despite that these mice showed no apparent change in general behavioral profile (Kojima et al., 2010). We have also reported that DAKO mice showed impairment of rapid homeostatic synaptic accumulation of the NMDA receptors (Aoki et al., 2009). In the present study we investigated more details of behavioral phenotypes in DAKO mice. We found that the impairment of contextual fear learning is age-dependent: the impairment was evident in mice older than 6 month old, but not in mice younger than 2-month old. Furthermore, we found that hippocampal CA1 LTP was significantly attenuated in DAKO mice older than 6-month old, whereas it was not altered in mice younger than 2-month old. Thus, our data suggest that drebrin A is involved in hippocampal synaptic plasticity underlying hippocampus-dependent learning in an age-dependent manner. Reference Kojima et al., Neuroscience 165:138–150, 2010 Aoki et al., J Comp Neurol 517:105–121, 2009
doi:10.1016/j.neures.2010.07.1527
P3-b14 Long-term potentiation induced in carbacholinduced  oscillation and gabazine-induced epileptic discharges in rat hippocampal slices Motoshi Nisimura , Kiyohisa Natsume Department of Brain Science and Engineering, Graduate school of Life Science and Systems Engineering
doi:10.1016/j.neures.2010.07.1529
P3-b16 The protein kinase M network as a bistable switch to store neuronal memory Hideaki Ogasawara 1 , Mitsuo Kawato 2 1
Rat hippocampus has the several rhythm, , , ␥ rhythm, sharp wave, and ripples. These rhythms are related to the memory process and thus they are functional. The hippocampus has also the pathological rhythm epileptic discharges. The discharges can cause the amnesia. So far we have been trying to find the different properties between the functional rhythm and the pathological rhythm using carbachol-induced  oscillations (CIBO) and gabazine-induced epileptic discharges (GIED) in rat hippocampal slices. One of the authors found that long-term potentiation (LTP) is facilitated during the generation of carbachol-induced oscillation. The synaptic plasticity induced in two rhythms CIBO and GIED has not yet been studied. So we studied whether LTP was facilitated in two rhythms in the present study. The schaffer collateral was antidromically stimulated using the concentric stimulation electrode and population excitatory postsynaptic potential (pEPSP) at the recurrent CA3 synapse was measured using the glass pipette at the stratum pyramidale. Theta-burst stimulation (TBS) consisting of five bursts separated by 200 msec. Each burst consisted of five rectangular current pulses (0.1 msec in duration) of 100 Hz. When TBS was done during CIBO, the slope of pEPSP significantly increased and the increase kept for at least 40 min. Thus LTP was induced. On the other hand it was not induced when TBS was done during GIED. CIBO is induced in an intermittent burst form with the inter burst interval of 20–30 s. TBS was done at the several phase of the interval, and at all phases LTP was induced. GIED was also induced regularly with the period of 10–20 s. TBS was also done at the various phase of the period, and LTP was not induced at all phases. These results suggest there is the difference of the induction of LTP between the functional and
National Institute of Information and Communications Technology Computational Neuroscience Laboratories
2
ATR
Protein kinase M (PKM) plays a key role in long-term memory maintenance. It is not known, however, how PKM stores information for long periods of time despite turnover of individual molecules. Bistability is ubiquitous in biochemical pathways and underlies cellular memory. By simulating the molecular network, we revealed that PKM forms a bistable system. Furthermore, the model was able to reproduce a variety of previous experimental results regarding synaptic plasticity and learning, further suggesting that it captures the essential mechanism for memory storage. We proposed in vitro and in vivo experiments to critically examine the validity of the model. doi:10.1016/j.neures.2010.07.1530
P3-b17 Persistent synaptic plasticity in the hippocampocortical pathway reproduced in vitro Yuki Oe , Kazuyuki Iijima, Takuhiro Kawakami, Keiko TominagaYoshino, Akihiko Ogura Department of Neuroscience, Osaka University Graduate School of Frontier Biosciences Behavioral studies suggest that information to be memorized is stored tentatively in the hippocampus and persistently in the cerebral cortex. To analyze cellular processes underlying the assumed information transfer and consolidation, we attempt to establish an in vitro model system that reproduces
e346
Abstracts / Neuroscience Research 68S (2010) e335–e446
the persistent synaptic plasticity in the cerebral cortex. We have reported that the repeated induction of LTP led to a slowly developing long-lasting enhancement in synaptic strength coupled with an increase in synapse density in the CA3-CA1 pathway of cultured rat hippocampal slices. We named this phenomenon RISE (Repeated-LTP-Induced Synaptic Enhancement) to discriminate it from the conventional single LTP and considered it as an in vitro reproduction of persistent structural plasticity. Since those specimens lacked output pathway from the hippocampus to the cortex, we here expanded the culture to include the subiculum and entorhinal cortex (EC), the output targets of CA1 neurons. The repeated induction of LTP by chemical means using forskolin in this expanded culture led to a synaptic enhancement in the cortical part instead of the hippocampal part, as revealed by a two-dimensional membrane potential assay using a voltage-sensitive dye/photodiode array apparatus. The density of postsynaptic spines also increased in the cortical part. Since forskolin-induced LTP was hardly detected in neither CA1-subiculum synapses nor CA1-subiculum-EC synapses in this culture, it is suggested that the RISE-like phenomenon in EC depended on a reverberant neural circuit involving the hippocampus and EC. The expanded slice culture thus provides an in vitro model system for the analyses of information transfer and its persistent storage in the cortex. doi:10.1016/j.neures.2010.07.1531
P3-b18 Long-lasting memory and information transfer: Time-dependent shift in the distribution of neurons activated upon the retrieval of conditioned fear Akihiko Ogura , Tomohiko Matsuzaki, Keiko Tominaga-Yoshino Department of Neuroscience, Osaka University Graduate School of Frontier Biosciences, Japan Based on behavioral observations of the subjects with brain injury, it is assumed that information acquired in the mammalian brain is temporarily stored in the hippocampus and transferred to the cerebral cortex following the passage of time. To pursue the cellular mechanism of such information transfer, if it occurs in intact model animal, we here examined the distribution of neurons activated by retrieval stimulation after the establishment of contextual fear conditioning in mice. Immunohistochemical staining of protein product of an immediately early gene Arc, a generally-accepted marker for activated neurons, revealed biased distributions of active neurons as below. As to the hippocampal CA1 region, active neurons were distributed denser in dorsal half (=septal side) than ventral half (=amygdalar side) immediately after memory acquisition, while they were distributed denser in ventral half than dorsal half 1 day after the acquisition and this bias disappeared in 7 days. As to the subiculum, the primary output target of the CA1 neurons, no dorsoventral bias was seen immediately after the acquisition, a ventral > dorsal bias occurred after 1 day and this bias was enhanced further in 7 days. These findings indicate that the information acquired is transferred from the hippocampus to the output target as days after the aquisition proceed. The analysis as to the entorhinal cortex, the secondary output target is presently in progress. doi:10.1016/j.neures.2010.07.1532
P3-b19 STDP can produce long-tail weight distributions Matthieu Gilson , Tomoki Fukai Lab for Neural Circuit Theory, Riken Brain Science Institute Spike-timing-dependent plasticity (STDP) is now an established mechanism for structuring connections between neurons. If there is a consensus on the time constants associated with its learning window, the parametrization of the weight dependence is still controversial, both on experimental and theoretical grounds. Here we consider a phenomenological model of pairwise STDP to examine the relationship between the weight dependence and asymptotic weight distribution. In particular, we focus on long-tail distributions (e.g. lognormal), which have been reported in electrophysiological experiments. We characterize a class of STDP rules that can produce such distributions and relate it to previously studied models, for which there is experimental support. Intrinsic or extrinsic noise in the weight modification rule is necessary to spread the weight distribution. Interestingly, no upper bound for the weights is necessary in our model and the scaling of potentiation and/or depression can be related to some physiological features, such as the density of neurotransmitter vesicles. For a neuron excited by input spike trains that have spike-time correlations, those with higher correlation strengths tend to be pushed to the tail of the distribution. In practice, only a few number of synapses may be significantly separated from the remain-
der. Such features have raised recent theoretical interest in terms of network neuronal dynamics and spiking information processing. The extension of our results to recurrent network is currently investigated. doi:10.1016/j.neures.2010.07.1533
P3-b20 Electrophysiological and molecular mechanisms of synaptic plasticity in the striatum Takashi Nakashi , Junichiro Yoshimoto, Jeff Wickens, Kenji Doya Okinawa Institute of Science and Technology The striatum receives glutamatergic input from the cortex and dopaminergic input from the substantia nigra. The plasticity of corticostriatal synapses play a major role in linking sensory, motor and cognitive information from the cortex with the dopaminergic reward signal. We previously constructed models of striatal spiny neurons at two levels: an electric compartmental model with a realistic cell morphology to predict the calcium response to glutamate and dopamine inputs (Nakano et al., 2009), and a molecular signaling pathway model within synaptic spines to predict the synaptic conductance change with calcium and dopamine inputs (Nakano et al., 2010). Here we analyzed the behavior of the combined system in order to clarify the mechanisms behind the striatal synaptic plasticity that is dependent on the cortical and dopamine inputs and their timing with the postsynaptic spikes. The major findings were: (1) The calcium response is maximal when both the cortical glutamate input and the dopamine input lead the postsynaptic spike. The response was enhanced while the cell was in the up state. (2) Either a strong calcium response or a combination of calcium and dopamine inputs caused long-term potentiation of the synapse. However, the effect of the timing of the calcium response and the dopamine input is minor. (3) In the combined system, the time integral of the calcium response is a good indicator of the synaptic plasticity. Thus the major effect of the dopamine timing is through its modulation of the calcium response rather than through the temporal response of the molecular signaling cascade. These predictions are being tested using calcium imaging and uncaging experiments. Reference:Nakano et al., ICANN, 2009Nakano et al., PLoS Comp Biol, 2010 doi:10.1016/j.neures.2010.07.1534
P3-b21 Stereological analysis on the age-related alterations in patterns of expression of astrocyte marker proteins S100, GFAP and Sox2 in the mouse hippocampus, with special reference to the dorsoventral differences Shozo Jinno Department Anat & Neurobiol, Grad Sch of Med Sci, Kyushu Univ, Fukuoka Glia plays essential physiological roles in the central nervous system. Astrocyte represents the largest population of glial cells, which is involved in various functions as follows: constitution of blood–brain barrier, regulation of neuronal nutrition, and removal of debris and excessive neuronal transmitters. During aging, various glial reactions were observed in the human brain, as well as in the rodent brain. This phenomenon has been generally accepted as a secondary and non-specific event following neuronal degeneration. However, increasing evidence suggests an early and direct involvement of astrocytes in the etiopathogenesis of memory and affective impairments in elderly people. The rodent hippocampus is anatomically and functionally segregated along the longitudinal (septotemporal) and transverse axes. Importantly, recent lesion studies suggest that the dorsal (septal) hippocampus plays a preferential role in spatial memory, while the ventral (temporal) hippocampus is involved in anxiety-related behaviors. Our latest optical disector analysis has shown that age-related decline in dentate neurogenesis is more severe in the ventral hippocampus than in the dorsal hippocampus. Taken together, these findings might explain why depression frequently precedes dementia in aged people. To further examine the precise onset mechanisms underlying cognitive impairment in old age, here we analyzed young adult and middle-aged mouse hippocampus, and stereologically estimated possible age-related alterations in the spatial distributions of astrocytes using three markers: S100, glial fibrillary acidic protein (GFAP), and sex determining region Y-box 2 (Sox2). The quantitative data showed that hippocampal astrocyte density changed with age accompanying considerable dorsoventral differences. Our present findings provide some key to understand the contribution of astrocytes to the hippocampus-dependent cognitive decline during senescence. doi:10.1016/j.neures.2010.07.1535
e345
the impairment of learning and memory known to be caused by estrogen depletion.
the pathological rhythms and the difference can differentiate the memory process induced in the two rhythms.
doi:10.1016/j.neures.2010.07.1526
doi:10.1016/j.neures.2010.07.1528
P3-b13 Construction of CaMKII-interacting protein network obtained from affinity purified proteins in silico and its experimental verification
P3-b15 Age-dependent impairments of hippocampal synaptic plasticity and hippocampus-dependent learning in drebrin A-specific knockout mice
Takafumi Yamada 1 , Akihiro Iwamatsu 2 , Takeshi Obayashi 3 , Kengo Kinoshita 3 , Shunji Ohsako 1
Nobuhiko Kojima 1 , Hiroki Yasuda 2 , Kenji Hanamura 1 , Tomoaki Shirao 1
1
1 Department of Neurobiology & Behavior, Gunma University Graduate School of Medicine, Maebashi 2 Education & Research Support Center, Gunma University Graduate School of Medicine, Maebashi
Tokyo Metro Inst for Neurosci, Tokyo 2 Protein Research Network, Inc, Yokohama 3 Grad Sch of Info Sci, Tohoku Univ, Sendai
CaMKII is a key kinase which involves in neural plasticity through its structural function and enzymatic activity. Drosophila CaMKII possessing single gene limits a molecular complexity derived from the isoforms relative to mammalian CaMKII. We therefore constructed a molecular network applying CaMKII-interacting proteins identified from Drosophila melanogaster. Although most of which 74 candidates identified by peptide mass fingerprinting have not been known as the CaMKII-interacting proteins, 70% of these were postsynaptic density proteins or synaptic vesicle’s proteins identified from proteome analyses, suggesting that these proteins were related to synaptic plasticity. We applied our coexpression database(db) [COXPRES db; http://coxpresdb.jp] providing coexpressed gene lists and networks concomitantly with protein-protein interaction. Networks related with translation and nucleocytoplasmic transport were successfully extracted by application of their human orthologs. NMDA receptor (NR) subunits were found to intervene between CaMKII and the identified proteins on a network. C terminal cytoplasmic region (Ct) of NR subunits which interact with signaling and scaffold proteins is important for synaptic plasticity. dCaMKII binds both Cts of dNR1 and dNR2 in GST pull down assay. Interestingly the dNR2 sequence is much shorter than vertebrate NR2 without any similar sequences and the known binding site different from dNR1 sequence similar to vertebrate NR1. The successful construction of network by human orthologues of different species and feature of conserved binding mode in nonconserved domain of NR imply that a common system works in synaptic plasticity between Drosophila and human. We will discuss about conservation of functional network and structural differences among organisms especially in NRs.
Dendritic spines are postsynaptic structures at excitatory synapses that play important roles in synaptic function. Actin-based cytoskeletal networks in dendritic spines determine the dynamics of spine morphology. Drebrin A, a neuron-specific isoform of drebrin, is a component of actin cytoskeletal structure in spines and is thought to have a pivotal role in spine morphogenesis and plasticity. To understand the role of drebrin A in brain functions, we generated drebrin A-specific knockout (DAKO) mice by deleting the drebrin A-specific exon. In DAKO mice drebrin E, another isoform of drebrin, continued to be expressed in the adult brain instead of drebrin A. These mice are viable and reveal no gross abnormalities in the brain. We have recently reported that DAKO mice showed impairment of contextual fear learning, despite that these mice showed no apparent change in general behavioral profile (Kojima et al., 2010). We have also reported that DAKO mice showed impairment of rapid homeostatic synaptic accumulation of the NMDA receptors (Aoki et al., 2009). In the present study we investigated more details of behavioral phenotypes in DAKO mice. We found that the impairment of contextual fear learning is age-dependent: the impairment was evident in mice older than 6 month old, but not in mice younger than 2-month old. Furthermore, we found that hippocampal CA1 LTP was significantly attenuated in DAKO mice older than 6-month old, whereas it was not altered in mice younger than 2-month old. Thus, our data suggest that drebrin A is involved in hippocampal synaptic plasticity underlying hippocampus-dependent learning in an age-dependent manner. Reference Kojima et al., Neuroscience 165:138–150, 2010 Aoki et al., J Comp Neurol 517:105–121, 2009
doi:10.1016/j.neures.2010.07.1527
P3-b14 Long-term potentiation induced in carbacholinduced  oscillation and gabazine-induced epileptic discharges in rat hippocampal slices Motoshi Nisimura , Kiyohisa Natsume Department of Brain Science and Engineering, Graduate school of Life Science and Systems Engineering
doi:10.1016/j.neures.2010.07.1529
P3-b16 The protein kinase M network as a bistable switch to store neuronal memory Hideaki Ogasawara 1 , Mitsuo Kawato 2 1
Rat hippocampus has the several rhythm, , , ␥ rhythm, sharp wave, and ripples. These rhythms are related to the memory process and thus they are functional. The hippocampus has also the pathological rhythm epileptic discharges. The discharges can cause the amnesia. So far we have been trying to find the different properties between the functional rhythm and the pathological rhythm using carbachol-induced  oscillations (CIBO) and gabazine-induced epileptic discharges (GIED) in rat hippocampal slices. One of the authors found that long-term potentiation (LTP) is facilitated during the generation of carbachol-induced oscillation. The synaptic plasticity induced in two rhythms CIBO and GIED has not yet been studied. So we studied whether LTP was facilitated in two rhythms in the present study. The schaffer collateral was antidromically stimulated using the concentric stimulation electrode and population excitatory postsynaptic potential (pEPSP) at the recurrent CA3 synapse was measured using the glass pipette at the stratum pyramidale. Theta-burst stimulation (TBS) consisting of five bursts separated by 200 msec. Each burst consisted of five rectangular current pulses (0.1 msec in duration) of 100 Hz. When TBS was done during CIBO, the slope of pEPSP significantly increased and the increase kept for at least 40 min. Thus LTP was induced. On the other hand it was not induced when TBS was done during GIED. CIBO is induced in an intermittent burst form with the inter burst interval of 20–30 s. TBS was done at the several phase of the interval, and at all phases LTP was induced. GIED was also induced regularly with the period of 10–20 s. TBS was also done at the various phase of the period, and LTP was not induced at all phases. These results suggest there is the difference of the induction of LTP between the functional and
National Institute of Information and Communications Technology Computational Neuroscience Laboratories
2
ATR
Protein kinase M (PKM) plays a key role in long-term memory maintenance. It is not known, however, how PKM stores information for long periods of time despite turnover of individual molecules. Bistability is ubiquitous in biochemical pathways and underlies cellular memory. By simulating the molecular network, we revealed that PKM forms a bistable system. Furthermore, the model was able to reproduce a variety of previous experimental results regarding synaptic plasticity and learning, further suggesting that it captures the essential mechanism for memory storage. We proposed in vitro and in vivo experiments to critically examine the validity of the model. doi:10.1016/j.neures.2010.07.1530
P3-b17 Persistent synaptic plasticity in the hippocampocortical pathway reproduced in vitro Yuki Oe , Kazuyuki Iijima, Takuhiro Kawakami, Keiko TominagaYoshino, Akihiko Ogura Department of Neuroscience, Osaka University Graduate School of Frontier Biosciences Behavioral studies suggest that information to be memorized is stored tentatively in the hippocampus and persistently in the cerebral cortex. To analyze cellular processes underlying the assumed information transfer and consolidation, we attempt to establish an in vitro model system that reproduces
e346
Abstracts / Neuroscience Research 68S (2010) e335–e446
the persistent synaptic plasticity in the cerebral cortex. We have reported that the repeated induction of LTP led to a slowly developing long-lasting enhancement in synaptic strength coupled with an increase in synapse density in the CA3-CA1 pathway of cultured rat hippocampal slices. We named this phenomenon RISE (Repeated-LTP-Induced Synaptic Enhancement) to discriminate it from the conventional single LTP and considered it as an in vitro reproduction of persistent structural plasticity. Since those specimens lacked output pathway from the hippocampus to the cortex, we here expanded the culture to include the subiculum and entorhinal cortex (EC), the output targets of CA1 neurons. The repeated induction of LTP by chemical means using forskolin in this expanded culture led to a synaptic enhancement in the cortical part instead of the hippocampal part, as revealed by a two-dimensional membrane potential assay using a voltage-sensitive dye/photodiode array apparatus. The density of postsynaptic spines also increased in the cortical part. Since forskolin-induced LTP was hardly detected in neither CA1-subiculum synapses nor CA1-subiculum-EC synapses in this culture, it is suggested that the RISE-like phenomenon in EC depended on a reverberant neural circuit involving the hippocampus and EC. The expanded slice culture thus provides an in vitro model system for the analyses of information transfer and its persistent storage in the cortex. doi:10.1016/j.neures.2010.07.1531
P3-b18 Long-lasting memory and information transfer: Time-dependent shift in the distribution of neurons activated upon the retrieval of conditioned fear Akihiko Ogura , Tomohiko Matsuzaki, Keiko Tominaga-Yoshino Department of Neuroscience, Osaka University Graduate School of Frontier Biosciences, Japan Based on behavioral observations of the subjects with brain injury, it is assumed that information acquired in the mammalian brain is temporarily stored in the hippocampus and transferred to the cerebral cortex following the passage of time. To pursue the cellular mechanism of such information transfer, if it occurs in intact model animal, we here examined the distribution of neurons activated by retrieval stimulation after the establishment of contextual fear conditioning in mice. Immunohistochemical staining of protein product of an immediately early gene Arc, a generally-accepted marker for activated neurons, revealed biased distributions of active neurons as below. As to the hippocampal CA1 region, active neurons were distributed denser in dorsal half (=septal side) than ventral half (=amygdalar side) immediately after memory acquisition, while they were distributed denser in ventral half than dorsal half 1 day after the acquisition and this bias disappeared in 7 days. As to the subiculum, the primary output target of the CA1 neurons, no dorsoventral bias was seen immediately after the acquisition, a ventral > dorsal bias occurred after 1 day and this bias was enhanced further in 7 days. These findings indicate that the information acquired is transferred from the hippocampus to the output target as days after the aquisition proceed. The analysis as to the entorhinal cortex, the secondary output target is presently in progress. doi:10.1016/j.neures.2010.07.1532
P3-b19 STDP can produce long-tail weight distributions Matthieu Gilson , Tomoki Fukai Lab for Neural Circuit Theory, Riken Brain Science Institute Spike-timing-dependent plasticity (STDP) is now an established mechanism for structuring connections between neurons. If there is a consensus on the time constants associated with its learning window, the parametrization of the weight dependence is still controversial, both on experimental and theoretical grounds. Here we consider a phenomenological model of pairwise STDP to examine the relationship between the weight dependence and asymptotic weight distribution. In particular, we focus on long-tail distributions (e.g. lognormal), which have been reported in electrophysiological experiments. We characterize a class of STDP rules that can produce such distributions and relate it to previously studied models, for which there is experimental support. Intrinsic or extrinsic noise in the weight modification rule is necessary to spread the weight distribution. Interestingly, no upper bound for the weights is necessary in our model and the scaling of potentiation and/or depression can be related to some physiological features, such as the density of neurotransmitter vesicles. For a neuron excited by input spike trains that have spike-time correlations, those with higher correlation strengths tend to be pushed to the tail of the distribution. In practice, only a few number of synapses may be significantly separated from the remain-
der. Such features have raised recent theoretical interest in terms of network neuronal dynamics and spiking information processing. The extension of our results to recurrent network is currently investigated. doi:10.1016/j.neures.2010.07.1533
P3-b20 Electrophysiological and molecular mechanisms of synaptic plasticity in the striatum Takashi Nakashi , Junichiro Yoshimoto, Jeff Wickens, Kenji Doya Okinawa Institute of Science and Technology The striatum receives glutamatergic input from the cortex and dopaminergic input from the substantia nigra. The plasticity of corticostriatal synapses play a major role in linking sensory, motor and cognitive information from the cortex with the dopaminergic reward signal. We previously constructed models of striatal spiny neurons at two levels: an electric compartmental model with a realistic cell morphology to predict the calcium response to glutamate and dopamine inputs (Nakano et al., 2009), and a molecular signaling pathway model within synaptic spines to predict the synaptic conductance change with calcium and dopamine inputs (Nakano et al., 2010). Here we analyzed the behavior of the combined system in order to clarify the mechanisms behind the striatal synaptic plasticity that is dependent on the cortical and dopamine inputs and their timing with the postsynaptic spikes. The major findings were: (1) The calcium response is maximal when both the cortical glutamate input and the dopamine input lead the postsynaptic spike. The response was enhanced while the cell was in the up state. (2) Either a strong calcium response or a combination of calcium and dopamine inputs caused long-term potentiation of the synapse. However, the effect of the timing of the calcium response and the dopamine input is minor. (3) In the combined system, the time integral of the calcium response is a good indicator of the synaptic plasticity. Thus the major effect of the dopamine timing is through its modulation of the calcium response rather than through the temporal response of the molecular signaling cascade. These predictions are being tested using calcium imaging and uncaging experiments. Reference:Nakano et al., ICANN, 2009Nakano et al., PLoS Comp Biol, 2010 doi:10.1016/j.neures.2010.07.1534
P3-b21 Stereological analysis on the age-related alterations in patterns of expression of astrocyte marker proteins S100, GFAP and Sox2 in the mouse hippocampus, with special reference to the dorsoventral differences Shozo Jinno Department Anat & Neurobiol, Grad Sch of Med Sci, Kyushu Univ, Fukuoka Glia plays essential physiological roles in the central nervous system. Astrocyte represents the largest population of glial cells, which is involved in various functions as follows: constitution of blood–brain barrier, regulation of neuronal nutrition, and removal of debris and excessive neuronal transmitters. During aging, various glial reactions were observed in the human brain, as well as in the rodent brain. This phenomenon has been generally accepted as a secondary and non-specific event following neuronal degeneration. However, increasing evidence suggests an early and direct involvement of astrocytes in the etiopathogenesis of memory and affective impairments in elderly people. The rodent hippocampus is anatomically and functionally segregated along the longitudinal (septotemporal) and transverse axes. Importantly, recent lesion studies suggest that the dorsal (septal) hippocampus plays a preferential role in spatial memory, while the ventral (temporal) hippocampus is involved in anxiety-related behaviors. Our latest optical disector analysis has shown that age-related decline in dentate neurogenesis is more severe in the ventral hippocampus than in the dorsal hippocampus. Taken together, these findings might explain why depression frequently precedes dementia in aged people. To further examine the precise onset mechanisms underlying cognitive impairment in old age, here we analyzed young adult and middle-aged mouse hippocampus, and stereologically estimated possible age-related alterations in the spatial distributions of astrocytes using three markers: S100, glial fibrillary acidic protein (GFAP), and sex determining region Y-box 2 (Sox2). The quantitative data showed that hippocampal astrocyte density changed with age accompanying considerable dorsoventral differences. Our present findings provide some key to understand the contribution of astrocytes to the hippocampus-dependent cognitive decline during senescence. doi:10.1016/j.neures.2010.07.1535