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T Tsumoto

Publications and source records attributed to T Tsumoto.

At least 73 records · Page 4Linked to original sources

Horizontal interactions between visual cortical neurones studied by cross-correlation analysis in the cat.

1. To explore the functional significance of horizontal neural connections in the extent of a 'hypercolumn' of the cat visual cortex, we carried out cross-correlation analysis of spike trains recorded simultaneously from a pair of neurones separated horizontally by less than 1 mm. 2. Significantly correlated firings, which were found in sixty-eight pairs of cells among 327 pairs analysed, were classified into three types on the basis of their functional implications: (1) excitatory interactions, (2) inhibitory interactions and (3) common inputs to both neurones of a pair from other sources. 3. Of these three types, common inputs were encountered most frequently. Excitatory interactions were always accompanied by common inputs. Inhibitory interactions were observed least frequently. 4. The proportion of cell pairs with correlated firings was high in pairs with a horizontal separation of less than 200 microns and decreased markedly with a horizontal separation of more than 400 microns. 5. Regarding laminar locations of cells, common inputs and excitatory interactions were often observed in layers II + III and V, whereas laminar bias was not seen in inhibitory interactions. 6. With respect to difference in orientation preference between two cells, all the three types of correlations were observed, mostly in cell pairs with a difference of less than 45 deg. In particular, common inputs and excitatory interactions were often seen in cell pairs with matched orientation preferences, but inhibitory interactions were found mostly in those with slightly different orientation preferences. In addition, common inputs and excitatory interactions tended to be found between cells with the same eye preference. 7. These results suggest that horizontal functional interactions exist mainly in a range of up to 400 microns as far as the extent of a hypercolumn of the visual cortex is concerned, and these interactions operate effectively between cortical cells with similar receptive field properties except for inhibitory interactions.

Action Potentials↗

Responses of neurons in the rat vestibular nuclei to static tilt stimulation.

The response properties of otolith afferent neurons have been analysed in the monkey and the cat. However, knowledge about the rat's responses to static tilt is scarce. To elucidate central information processing of the otolith system, responses to static tilt were analysed in the rat vestibular nuclei neurons.

Animals↗

Release of glutamate and aspartate from the visual cortex of the cat following activation of afferent pathways.

To test the possibility that glutamate (Glu) and aspartate (Asp) are transmitters at geniculo-cortical synapses in the visual cortex of the cat, we studied the release of amino acids from the striate cortex consequent upon visual and electrical stimulation of the dorsal lateral geniculate nucleus (LGN) and of the optic tract, using push-pull cannulae. We perfused a discrete region that included layer IV of the cortex with an artificial cerebrospinal fluid (aCSF) and analysed the amino acid content of these perfusates by high-performance liquid chromatography (HPLC). Significant increases only of Glu and Asp were obtained among all 17 amino acids measured, except for gamma-aminobutyric acid (GABA), during electrical stimulation of the afferent pathways. Visual stimulation by stroboscopic diffuse flashes of light increased the level of Glu released, but did not change that of Asp significantly. The level of GABA released did not change during diffuse flash stimulation, suggesting that the increase in Glu was not derived from cortical neurons. The increases in release of Glu/Asp were not seen when the perfusion medium was replaced with a Ca2(+)-free, high-Mg2(+)-containing solution. The basal (resting) release of Glu/Asp in the absence of stimulation also was decreased during perfusion with Ca2(+)-free/high-Mg2+ solutions. Intraocular injections of a sodium channel blocker, tetrodotoxin (TTX), resulted in a remarkable decrease in the basal release of Glu. These results suggest that Glu is released as in excitatory synaptic transmitter at least from terminals of geniculo-cortical afferents and Asp from axons of a certain type of visual cortical neuron.

Animals↗

Actions of excitatory amino acid antagonists on synaptic inputs to the rat medial vestibular nucleus: an electrophysiological study in vitro.

The actions of excitatory amino acid (EAA) antagonists on synaptic inputs to neurons in the rat medial vestibular nucleus (MVN) from ipsilateral vestibular afferents and vestibular commissures were studied in brain stem slice preparations. Antagonists used were 2-amino-5-phosphonovalerate (APV), a selective antagonist for the N-methyl-D-aspartate (NMDA) type of EAA receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective antagonist for the quisqualate/kainate (non-NMDA) type of EAA receptors and kynurenate (KYNA), a broad spectrum antagonist for the three types of EAA receptors. MVN neurons were classified as having mono- or polysynaptic inputs from vestibular afferents and commissural fibers by calculating synaptic delay. An application of APV through the perfusion medium suppressed 82% of cells activated monosynaptically from commissures, while it suppressed only 9% of cells activated monosynaptically from vestibular afferents. The application of KYNA proved much less selective, suppressing 83% of the former group of cells and 93% of the latter. CNQX suppressed almost all the cells of both groups. The sensitivity of monosynaptic inputs to KYNA, CNQX or APV was not significantly different from that of polysynaptic inputs irrespective of sources of inputs. These results suggest that excitatory synaptic inputs to MVN neurons are mediated mainly through non-NMDA type of EAA receptors from vestibular afferents and through NMDA as well as non-NMDA types of EAA receptors from commissures.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Blockade of synaptic transmission from hair cells to auditory afferent nerves by 6-cyano-2,3-dihydroxy-7-nitroquinoxaline, a selective non-NMDA receptor antagonist.

6-Cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) is a new, potent and selective competitive antagonist for the non-N-methyl-D-aspartate (non-NMDA) type of excitatory amino acids receptors. We studied the effect of CNQX on the compound auditory nerve action potential (CAP), cochlear microphonics (CM), summating potential (SP) and endocochlear potential (EP). CNQX in doses of 10-20 microM reduced the CAP magnitude and increased the N1 latency without affecting the CM, SP, or EP. Parallel shifts of CAP amplitude- and latency-intensity functions were observed. The CAP suppressed by 10 microM CNQX was completely reversed by a 10-min washout with artificial perilymph. As 10 microM and 20 microM CNQX seem to exert a selective antagonism for non-NMDA receptors, results indicate that non-NMDA receptors play a major role in synaptic transmission from hair cells to auditory afferent nerves.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Excitatory amino acid transmitters and their receptors in neural circuits of the cerebral neocortex.

In 1954, L-glutamate (Glu) and L-aspartate (Asp) were first suggested as being excitatory synaptic transmitters in the cerebral cortex. Since then, evidence has mounted steadily in favor of the view that Glu and Asp are major excitatory transmitters in the neocortex. Many of the experimental studies which reported how Glu/Asp came to satisfy the criteria for transmitters in the neocortex are reviewed here, according to the methods employed. Since the question of which particular synaptic sites in cortical neural circuits Glu/Asp operate as excitatory transmitters has not previously been reviewed, particular attention is given to efferent, afferent and intrinsic neural circuits of the visual and somatosensory cortices, where circuitry is relatively clearly delineated. Recent studies using chemical assays of released amino acids, high-affinity uptake mechanisms of Glu/Asp from nerve terminals, the direct micro-iontophoretic administration of Glu/Asp antagonists, and immunocytochemical techniques have demonstrated that almost all corticofugal efferent projections employ Glu/Asp as excitatory synaptic transmitters. Evidence indicating that thalamocortical afferent projections, including geniculocortical projections and some intrinsic connections are glutamatergic, is also reviewed. Thus, the results highlighted here indicate that the main framework of neocortical circuitry is operated by Glu/Asp. Pharmacological studies indicate that synaptic receptors for Glu/Asp can be classified into a few subtypes, including N-methyl-D-aspartate (NMDA) and quisqualate/kainate (non-NMDA) types. Some evidence indicating the sites of operation of NMDA and non-NMDA receptors in neocortical circuitry is reviewed, and the distinct, functional significance of these two types of Glu/Asp receptors in information processing in the neocortex is proposed.

Amino Acids↗

Contribution of quisqualate/kainate and NMDA receptors to excitatory synaptic transmission in the rat's visual cortex.

Action of antagonists for excitatory amino-acid (EAA) receptors on extracellularly and intracellularly recorded responses of layer II/III cels to electrical stimulation of the underlying white matter were studied in a slice preparation of rat's visual cortex. Antagonists used were 2-amino-5-phosphonovalerate (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), which are selective antagonists for EAA receptors of N-methyl-D-aspartate (NMDA) and quisqualate/kainate (non-NMDA) type, respectively. In extracellular recordings, it was found that responses of almost all of the cells were suppressed by CNQX. In contrast, sensitivity to APV was different between cells with short-and long-latency responses; 81% of the former responses were not suppressed by APV, while about a half of the latter were suppressed. Excitatory postsynaptic potentials (EPSPs) evoked by white-matter stimulation were recorded intracellularly from 42 neurons. Most of polysynaptically elicited EPSPs were sensitive to AVP, whereas the majority of monosynaptic EPSPs, were not. CNQX almost completely suppressed EPSPs irrespective of monosynaptically or polysynaptically evoked, but in some cases slow EPSPs with low amplitude were spared. These CNQX-resistant EPSPs were elicited polysynaptically and had an anomalous voltage dependence, a characteristic of NMDA receptors. It is suggested that non-NMDA receptors contribute dominantly to first-order synaptic transmission while NMDA receptors participate substantially in second-order transmission so as to serve as a booster of outputs from visual cortex.

2-Amino-5-phosphonovalerate↗

Long-term depression but not potentiation is induced in Ca(2+)-chelated visual cortex neurons.

An entry of Ca2+ into postsynaptic sites may play a role in the induction of long-term potentiation (LTP) of synaptic transmission in the visual cortex. To test this hypothesis, a Ca(2+)-chelator was injected into layer II/III neurons of sliced visual cortex obtained from young rats, and excitatory postsynaptic potentials (EPSPs) of these cells to test stimulation of the white matter were observed before and after tetanic stimulation of the same site. To confirm the effectiveness of the tetanus, field potentials reflecting the activities of many cells were recorded with another extracellular electrode. The chelator injection led to long-term depression (LTD) of EPSPs following tetanic stimuli which simultaneously induced LTP of field potentials derived from unchelated cells in most of the slices tested. This suggests that a low concentration of post-synaptic, free Ca2+, when associated with tetanic inputs, may lead to LTD while a rise of Ca2+ may lead to LTP.

Animals↗

Long-term potentiation and depression in the cerebral neocortex.

Long-term potentiation of synaptic efficacy following tetanic synaptic inputs was described originally in the hippocampus, and it has been studied extensively based on the hypothesis that it represents a synaptic model of learning and memory in the brain. In the cerebral neocortex, studies on LTP have burgeoned later, and have progressed less rapidly than those in the hippocampus. Recently, however, experimental data describing the phenomenology and the mechanisms underlying LTP have accumulated in the neocortex, particularly in the visual, somatosensory, and motor cortices. In the developing visual cortex, LTP has been induced by afferent tetanic stimulation at relatively low frequencies, for long duration. Thus, particular attention has been given to parameters of the tetanus optimal for the induction of cortical LTP, and the differences between these and those effective in inducing hippocampal LTP have been reviewed. In the motor cortex, the associative LTP following combined activation of separate sites as well as homosynaptic LTP following activation of single pathways have been reported and these types of synaptic plasticity have been suggested as being a basis for a certain type of motor learning. Long-lasting depression (LTD) of synaptic efficacy also has been reported in the developing visual cortex and suggested as a neural basis for experience-dependent modifications of visual cortical neurons. LTD has been found in other areas of the neocortex as well, although the probability of its induction is relatively low and its functional significance is not yet clear. Among the possible mechanisms for the induction of LTP and LTD, those including the involvement of NMDA receptors, protein kinase C, Ca2+/calmodulin-dependent kinase II, and membrane-associated cytoskeletal proteins have been reviewed, although the results obtained so far are only fragmentary and are premature for definitive conclusions to be drawn.

Animals↗

Actions of excitatory amino acid antagonists on synaptic potentials of layer II/III neurons of the cat's visual cortex.

Actions of excitatory amino acid (EAA) antagonists on the responses of cells in layers II/III and IV of the cat's visual cortex to stimulation of layer VI and the underlying white matter were studied in slice preparations. Antagonists used were 2-amino-5-phosphonovalerate (APV), a selective antagonist for the N-methyl-D-aspartate (NMDA) type of EAA receptors, and kynurenate, a broad-spectrum antagonist for the three types of EAA receptors. In extracellular recordings it was demonstrated that most of the layer II/III cells were sensitive to APV, while the great majority of the layer IV cells were not. By contrast, kynurenate suppressed the responses completely in both layers. Excitatory post-synaptic potentials (EPSPs) evoked by stimulation of layer VI and the while matter were recorded intracellularly from layer II/III neurons. To determine whether the EPSPs were elicited mono- or polysynaptically, the synaptic delay for each EPSP was calculated from a pair of onset latencies of EPSPs evoked by stimulation of the two sites. Forty-two percent of the layer II/III cells were classified as having monosynaptic EPSPs. In 60% of these monosynaptic cells, the rising slope of the EPSPs was reduced by APV while in the other 40%, it was not. In the former (APV-sensitive cells), subtraction of the APV-sensitive component from the total EPSP indicated that the onset latency of the NMDA receptor-mediated component was roughly equal to that of the non-NMDA component. In the latter (APV-resistant cells), only the slowly-decaying component was in part mediated by NMDA receptors. The conduction velocities of the afferent fibers innervating APV-resistant cells were slower than those of the APV-sensitive cells, suggesting that both types of cells are innervated by different types of afferents. The polysynaptic EPSPs of almost all layer II/III cells were sensitive to APV. The subtraction method indicated that the NMDA component had about the same magnitude as the non-NMDA components. When the slices were superfused by a Mg2+-free solution, the EPSPs were potentiated dramatically, but this potentiation was reduced to the control level during the administration of APV. Similarly, APV-sensitive components were potentiated during the administration of bicuculline, a selective antagonist for gamma-aminobutyric acid receptors of A type. These results suggest that NMDA receptors participate, at varying degrees, in excitatory synaptic transmission at most layer II/III cells in the cat's visual cortex, and their actions appear to be regulated by intracortical inhibition.

2-Amino-5-phosphonovalerate↗

Long-term potentiation and N-methyl-D-aspartate receptors in the visual cortex of young rats.

1. Long-term potentiation (LTP) of synaptic transmission following tetanic stimulation of the white matter was studied by recording extracellular field potentials and intracellular synaptic potentials from layer II/III of visual cortical slices from young rats ranging in age from 21 to 40 days. 2. Single shocks applied to the white matter at 0.1 Hz, used as test stimuli, elicited field potentials that consisted of primary and secondary components. The removal of Ca2+ ions from the perfusate allowed identification of the secondary component as originating postsynaptically and the primary one as reflecting a mixture of antidromic and postsynaptic potentials. 3. Tetanic stimulation at 5 Hz for 60 s was delivered to the white matter and field potentials were observed for 20 min to 9 h after the tetanus. LTP was defined as being present when the response displayed more than a 20% increase in amplitude of the Ca2+-sensitive components 20 min after the tetanus. LTP was induced in twelve of twenty-three slices tested, and this potentiation lasted throughout the period of observation. The average magnitude of potentiation was 147.8 +/- 28.4% of the control value for the twelve slices. 4. Administration of D,L-2-amino-5-phosphonovalerate (APV), an antagonist selective for N-methyl-D-aspartate (NMDA)-preferring receptors, slightly reduced the amplitudes of Ca2+-sensitive components of the field potentials. The average magnitude of reduction was 80.2 +/- 15.3% of the pre-drug control values. In the presence of APV, LTP was induced in only one slice of twelve tested. 5. Stable intracellular recordings were obtained from twenty-three cells from layer II/III. Excitatory postsynaptic potentials (EPSPs) evoked by white matter stimulation had mean onset and peak latencies of 4.1 and 11.3 ms, respectively. In some cells these fast EPSPs were followed by another slow EPSP with a much longer latency and higher amplitude. Administration of APV revealed further that the fast EPSPs consisted of two components, i.e. early and late components. 6. Tetanization of the white matter induced long-lasting enhancement of EPSPs in eight of twelve cells tested. In five of these eight cells, fast EPSPs were enhanced in amplitude and in the remaining three cells, slow EPSPs appeared de novo after the tetanus. 7. APV reduced the amplitudes of the fast EPSPs and abolished the slow EPSPs if present. The average magnitude of reduction for the fast EPSPs was 65.6 +/- 15.1% and this reduction was due mainly to an elimination of the late component.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

Inhibition contributes to orientation selectivity in visual cortex of cat.

Neurons in the visual cortex are selectively responsive to light or dark bars presented at particular orientations. On the basis of physiological data, this orientation selectivity is hypothesized as being due at least partially to intracortical inhibitory mechanisms. But this hypothesis has been challenged by intracellular recordings indicating that excitatory inputs themselves are orientation-selective, so inhibition may not contribute to the observed selectivity. Also, there is controversy about the presence of intracortical horizontal connections mediating inhibition for selectivity and about the theoretical validity of such inhibitory connections. Using cross-correlation analysis of the activities of two neurons recorded simultaneously, we find that inhibitory interactions exist between cells with somewhat different, but not orthogonal, orientation preferences. This suggests that intracortical horizontal inhibition operates between 'orientation columns' to sharpen the orientation tuning of cortical neurons.

Action Potentials↗

Immunohistochemical localization of a membrane-associated, 4.1-like protein in the rat visual cortex during postnatal development.

Expression and localization of a membrane-associated protein, an analog of erythrocyte protein 4.1, in the visual cortex were immunohistochemically studied in the rat, ranging in age from newborn to adult. In the adult, dendrites and somas of layer V pyramidal cells were stained by the antiprotein 4.1 antibody. In most of these immunoreactive neurons, the plasma membrane seemed to be preferentially stained. Neurons located in layers II and III of the cortex were only faintly stained, and those in layers IV and VI were not stained. At birth, the immunoreactivity was already present in pyramidal cells located in the upper part of the cortical subplate. Immature neurons located in the cortical plate were not stained by the antibody, suggesting that the 4.1-like protein is expressed only in the neurons that have differentiated or are differentiating. At postnatal days 2-8, immunoreactive neurons were dramatically increased in layers V and VI and intense labeling was seen at the apical dendrites of layer V pyramidal cells. Most of the stained processes of these and other neurons showed a sign of rapid dendritic growth, i.e., growth cones and filopidia. At days 10-17, the basal dendrites of pyramidal cells in layers II and III became detectable, although still slender. At days 20-37, these dendrites in layers II, III, and V became intensely immunoreactive, and dendritic spines were visualized by the antibody. Throughout all the ages, axons of neurons and neuroglia were not stained by the antibody. Also, most of the neurons in layer IV of the cortex were not immunoreactive. These results suggest that the 4.1-like protein is abundantly expressed in growing parts of the dendrites and spines. A hypothesis that this protein may play a role in synaptic plasticity in the developing visual cortex is discussed.

Aging↗

Actions of excitatory amino acid antagonists on geniculo-cortical transmission in the cat's visual cortex.

To test the possibility that glutamate and aspartate are transmitters at geniculo-cortical synapses and to elucidate which type of receptors for the excitatory amino acids (EAA) operate at these synapses, we studied effects of microiontophoretic administration of EAA antagonists on the responses of visual cortical neurons to afferent electrical and visual stimulation in the cat. The antagonists used were kynurenate, a non-selective antagonist for all classes of EAA receptors and 2-amino-5-phosphonovalerate (APV), a selective antagonist for N-methyl-D-aspartate (NMDA)-preferring receptors. The administration of kynurenate suppressed responses elicited by electrical stimulation of the dorsal lateral geniculate nucleus (LGN) and optic chiasm (OX) of 65% of the cells tested. This suppression was more marked for the short-latency responses which were evoked monosynaptically from the LGN, than for the longer-latency responses. In contrast with the effectiveness of kynurenate, APV failed to suppress electrically and visually elicited responses in 66% of the cortical cells. Such differences between kynurenate and APV were particularly prominent in layers IV and VI, which receive direct inputs from the LGN, but were less marked or were not recognizable in layers II + III and V. These results support previous suggestions that EAAs may be excitatory transmitters in the cerebral cortex, at least at geniculo-cortical synapses, and indicate further that EAA receptors of the "non-NMDA type" may be involved in afferent synaptic transmission in the cat's visual cortex.

2-Amino-5-phosphonovalerate↗

Dark-reared cats: responsitivity of cortical cells influenced pharmacologically by an inhibitory antagonist.

When studied physiologically, dark-reared kittens exhibit abnormal responses. Specifically, cortical cells respond poorly, if at all, to visual stimulation. In the preceding paper (Ramoa et al. 1986) we showed that iontophoretic application of an excitatory amino acid allows all cells in this preparation to be excited or suppressed by visual stimuli. In the current study, we have pursued this finding by studying additional dark-reared kittens using iontophoretic application of an inhibitory antagonist, bicuculline methiodide (BIC). Responses of most cells studied were affected by application of BIC. Of cells which were originally weak or unresponsive, 76% became clearly responsive with application of BIC. Of cells which responded without BIC and were orientation-selective, only 33% lost selectivity during application of BIC. Considered together, these findings suggest functional inhibitory input in dark-reared animals which appears to differ from that in normal kittens with respect to its role in selectivity for stimulus orientation.

Animals↗

Postnatal development of immunohistochemically localized spectrin-like protein (calspectin or fodrin) in the rat visual cortex: its excessive expression in developing cortical neurons.

Postnatal development of the expression and localization of a membrane-associated cytoskeletal protein, calspectin (fodrin or brain spectrin), in the visual cortex, was immunohistochemically studied in newborn to adult rats, by using an anti-calspectin antibody. At birth, calspectin-immunoreactivity was already present at the plasma membrane and in the cytoplasm of neurons which were mostly pyramidal cells located in the upper part of the cortical subplate. Immature neurons located in the cortical plate were not stained by the antibody, suggesting that calspectin is expressed only in neurons which have differentiated or are differentiating. At postnatal days 2 to 7, immunoreactive neurons were dramatically increased in layers V and VI and very intense labelling was seen in the apical dendrites of layer V pyramidal cells. Most of the stained processes of these and other neurons showed signs of rapid dendritic growth, i.e. non-terminal as well as terminal growth cones and filopodia. At days 10 to 17, dendrites of pyramidal cells in layers II and III became clearly detectable, although still slender. At days 24 to 34, the basal dendrites of pyramidal cells in layers II, III and V became intensely immunoreactive and dendritic spines were visualized by the antibody. In the adult, however, the calspectin immunoreactivity became very weak and spines were not recognizable. At all the ages, axons and neuroglia were unstained. Also, most of the neurons in layer IV of the cortex were not immunoreactive. These results suggest that calspectin is most abundantly expressed in growing parts of the dendrites and spines. A hypothesis that calspectin may play a role in synaptic plasticity in the developing visual cortex is discussed.

Aging↗