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Biomedical subjects

Yumiko Yoshimura

Publications and source records attributed to Yumiko Yoshimura.

10 recordsLinked to original sources

High-frequency stimulation together with adrenoceptor activation facilitates the maintenance of long-term potentiation at visual cortical inhibitory synapses.

Long-term potentiation (LTP) at inhibitory synapses of rat visual cortex requires firing of presynaptic cells for maintenance, at least at a low frequency. We examined the roles of adrenoceptors in this LTP maintenance. Although high-frequency stimulation (HFS) failed to produce LTP in normal Ca2+ medium, it produced pathway-specific LTP with addition of noradrenaline to the medium soon after HFS. However, this LTP disappeared after washout of noradrenaline. HFS applied during noradrenaline application produced LTP persisting even after washout, indicating that HFS together with adrenoceptor activation makes the adrenergic facilitation enduring. After washout, LTP was produced further by HFS of the conditioned, but not the unconditioned, pathway by the first HFS. Pharmacological examination demonstrated that alpha2 and beta, but not alpha1, receptors facilitated LTP maintenance synergistically. Bath application, but not postsynaptic loading, of either the adenylyl cyclase activator forskolin or the protein kinase C (PKC) activator phorbol ester facilitated LTP maintenance. These results suggest that adrenergic facilitation of LTP maintenance is mediated by presynaptic adrenoceptors via a subfamily of adenylyl cyclases stimulated by Gsalpha, Gibetagamma, and PKC. Thus, it is likely that the activity of noradrenergic afferents takes part in the control of LTP duration at visual cortical inhibitory synapses.

Adaptation, Physiological↗

Fine-scale specificity of cortical networks depends on inhibitory cell type and connectivity.

Excitatory cortical neurons form fine-scale networks of precisely interconnected neurons. Here we tested whether inhibitory cortical neurons in rat visual cortex might also be connected with fine-scale specificity. Using paired intracellular recordings and cross-correlation analyses of photostimulation-evoked synaptic currents, we found that fast-spiking interneurons preferentially connected to neighboring pyramids that provided them with reciprocal excitation. Furthermore, they shared common fine-scale excitatory input with neighboring pyramidal neurons only when the two cells were reciprocally connected, and not when there was no connection or a one-way, inhibitory-to-excitatory connection. Adapting inhibitory neurons shared little or no common input with neighboring pyramids, regardless of their direct connectivity. We conclude that inhibitory connections and also excitatory connections to inhibitory neurons can both be precise on a fine scale. Furthermore, fine-scale specificity depends on the type of inhibitory neuron and on direct connectivity between neighboring pyramidal-inhibitory neuron pairs.

Action Potentials↗

Excitatory cortical neurons form fine-scale functional networks.

The specificity of cortical neuron connections creates columns of functionally similar neurons spanning from the pia to the white matter. Here we investigate whether there is an additional, finer level of specificity that creates subnetworks of excitatory neurons within functional columns. We tested for fine-scale specificity of connections to cortical layer 2/3 pyramidal neurons in rat visual cortex by using cross-correlation analyses of synaptic currents evoked by photostimulation. Recording simultaneously from adjacent layer 2/3 pyramidal cells, we find that when they are connected to each other (20% of all recorded pairs) they share common input from layer 4 and within layer 2/3. When adjacent layer 2/3 neurons are not connected to each other, they share very little (if any) common excitatory input from layers 4 and 2/3. In contrast, all layer 2/3 neurons share common excitatory input from layer 5 and inhibitory input from layers 2/3 and 4, regardless of whether they are connected to each other. Thus, excitatory connections from layer 4 to layer 2/3 and within layer 2/3 form fine-scale assemblies of selectively interconnected neurons; inhibitory connections and excitatory connections from layer 5 link neurons across these fine-scale subnetworks. Relatively independent subnetworks of excitatory neurons are therefore embedded within the larger-scale functional architecture; this allows neighbouring neurons to convey information more independently than suggested by previous descriptions of cortical circuitry.

Action Potentials↗

Targeted gene delivery to telencephalic inhibitory neurons by directional in utero electroporation.

Telencephalic inhibitory neurons originate in the ganglionic eminences and migrate to the cerebral cortex following a tangential trajectory, before they differentiate and integrate within the local circuitry. Current studies of interneuron development and function benefit from the use of knock-out and transgenic mice, whereas none take advantage of the versatility of in utero electroporation. Here, we show how in utero electroporation can be directed to the ganglionic eminences to specifically target gene expression to interneurons. Electroporation of GFP-encoding plasmids into the ganglionic eminences results in selective labeling of migrating interneurons during development. In the adult brain of electroporated animals, a wide variety of cortical, hippocampal and olfactory bulb interneurons are labeled. We also show that GFP-expressing interneurons can be visualized in living slices of adult cerebral cortex, where they display normal electrophysiological properties. Photostimulation studies using acute slices show that cortical GFP+ interneurons receive normal, layer-specific synaptic input, indicating that these neurons integrate within the local cortical circuitry. Ganglionic eminence-directed in utero electroporation is therefore an effective, rapid, and versatile method of selectively transfecting telencephalic interneurons, optimal for both developmental studies and adult functional studies.

Animals↗

Presynaptic activity and Ca2+ entry are required for the maintenance of NMDA receptor-independent LTP at visual cortical excitatory synapses.

We have shown that some neural activity is required for the maintenance of long-term potentiation (LTP) at visual cortical inhibitory synapses. We tested whether this was also the case in N-methyl-d-aspartate (NMDA) receptor-independent LTP of excitatory connections in layer 2/3 cells of developing rat visual cortex. This LTP occurred after 2-Hz stimulation was applied for 15 min and always persisted for several hours while test stimulation was continued at 0.1 Hz. When test stimulation was stopped for 1 h after LTP induction, only one-third of the LTP instances disappeared, but most did disappear under a pharmacological suppression of spontaneous firing, indicating that LTP maintenance requires either evoked or spontaneous activities. LTP was totally abolished by a temporary blockade of action potentials with lidocaine or the removal of extracellular Ca(2+) after LTP induction, but it persisted under a voltage clamp of postsynaptic cells or after a temporary blockade of postsynaptic activity with the glutamate receptor antagonist kynurenate, suggesting that LTP maintenance requires presynaptic, but not postsynaptic, firing and Ca(2+) entry. More than one-half of the LTP instances were abolished after a pharmacological blockade of P-type Ca(2+) channels, whereas it persisted after either L-type or Ni(2+)-sensitive Ca(2+) channel blockades. These results show that the maintenance of NMDA receptor-independent excitatory LTP requires presynaptic firing and Ca(2+) channel activation as inhibitory LTP, although the necessary level of firing and Ca(2+) entry seems lower for the former than the latter and the Ca(2+) channel types involved are only partly the same.

Anesthetics, Local↗

Two forms of synaptic plasticity with distinct dependence on age, experience, and NMDA receptor subtype in rat visual cortex.

In visual cortex, NMDA receptor (NMDAR) properties depend primarily on NR2A and NR2B subunits, and NR2 subunit composition changes with age and visual experience. We examined the roles of these NR2 subunits in activity-dependent long-term modification of synaptic responses, which were evoked in layer 2/3 cells by stimulation of layer 4 in rat visual cortical slices. We used theta-burst stimulation (TBS) of presynaptic fibers or low-frequency stimulation paired with postsynaptic depolarization, which has been commonly used to induce NMDAR-dependent long-term potentiation (LTP) in visual cortex. In pyramidal cells, however, TBS produced long-term depression (LTD) at inhibitory synapses rather than LTP at excitatory synapses. This was observed in association with LTP of extracellular field potentials that reflect postsynaptic potentials in a population of cells (field-LTP). This result is inconsistent with the previous view that field-LTP reflects LTP of excitatory connections. However, pairing stimulation produced LTP at excitatory synapses of pyramidal cells frequently during development but rarely in adulthood. In contrast, inhibitory LTD and field-LTP occurred similarly in both developing and mature cortex. Experiments using NR2B selective and NR2 subunit nonselective NMDAR antagonists demonstrated that NR2A- and NR2B-containing NMDARs contribute selectively to inhibitory LTD-field-LTP and excitatory LTP, respectively. In addition, we found that the developmental decline in the NR2B component was paralleled by a decline in the incidence of excitatory LTP, and these declines were both prevented by dark rearing. These results implicate NR2 subunit composition in the regulation of neocortical plasticity and demonstrate differential subunit regulation at inhibitory and excitatory connections.

Age Factors↗

Age and experience dependence of N-methyl-D-aspartate receptor-independent long-term potentiation in rat visual cortex.

Dark rearing prolongs the critical period for experience-dependent modification of visual cortical functions. To test whether long-term potentiation (LTP) could potentially underlie this modification, we studied the age and experience dependence of LTP, induced in layer 2/3 cells by layer 4 stimulation continued for 15 min at 2 Hz, in rat visual cortical slices. This LTP was independent of N-methyl-D-aspartate receptor (NMDAR) activation, but it likely required Ni(2+)-sensitive Ca(2+) channel activation for induction. LTP occurred frequently during development, but rarely in adulthood. Dark rearing prevented this developmental decline. These age- and experience-dependent changes were demonstrated in both excitatory postsynaptic potentials recorded from pyramidal cells under a local blockade of inhibition and extracellular field potentials. These results suggest the possible involvement of NMDAR-independent LTP in the experience-dependent development of visual cortex.

2-Amino-5-phosphonovalerate↗

Postsynaptic firing produces long-term depression at inhibitory synapses of rat visual cortex.

High-frequency activation of excitatory synapses produces long-term depression (LTD) at inhibitory synapses in rat visual cortex. The LTD generation mechanism was studied by recording inhibitory postsynaptic potentials from layer V cells in response to layer IV stimulation under pharmacological blockade of excitatory synaptic transmission. LTD occurred after depolarizing current pulses applied to postsynaptic cells elicited repetitive firing. LTD induction was facilitated by a bath application of an L-type Ca(2+) channel activator, 1,4-Dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl) phenyl]-3-pyridinecarboxylic acid, methyl ester (BAY K 8644), while it was prevented by either the bath application of L-type Ca(2+) channel blocker nifedipine or postsynaptic loading of Ca(2+) chelator 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N',-tetraaceticacid (BAPTA). These results suggest that LTD induction is at least partly mediated by Ca(2+) entry through L-type Ca(2+) channels in association with postsynaptic action potentials.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Suppressive effects of receptive field surround on neuronal activity in the cat primary visual cortex.

Effects of sinusoidal grating stimulus presented outside the classical receptive field (CRF) on neuronal responses were studied in the primary visual cortex of anaesthetized cats. Among 101 cells electrophysiologically recorded, the predominant effect of the stimulus in the receptive field surround (SRF) was the suppression of responses to the CRF stimulation, and the SRF grating suppressed them up to 56% of the responses (44% suppression) to the CRF stimulus alone. The strong suppression was observed more often in layer II/III cells than in other layers and in complex cells more often than in simple cells. The modulatory effects by SRF stimulus might be enhanced by the cortical recurrent excitation particularly in the superficial layers. We also examined whether the modulation by the surround grating exhibits a differential effect according to the presence or absence of figure-ground segregation in the stimulus configuration. For this purpose, effects of stimulus configuration with orientation-, direction-contrast or relative spatial phase difference between CRF and SRF stimuli (figure-ground segregated configuration) were compared with those of uniform configuration of stimulus (non-segregated configuration). There was a population of cells, which exhibited significantly stronger suppression with non-segregated configuration than with figure-ground segregated configuration. Such differential modulation of response by the SRF stimulus in the primary visual cortex is a possible basis of perceptual figure-ground segregation.

Animals↗