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S F Takagi

Publications and source records attributed to S F Takagi.

At least 19 recordsLinked to original sources

Olfactory input to the lateral hypothalamus of the old world monkey.

Responses of lateral hypothalamic neurons to 8 odors were studied in chronic unanesthetized old world monkeys (Macaca irus). Many neurons (54.5%) responded to a single odor only, and the number of neurons responding to 2, 3 and 4 odors decreased successively. No neuron responded to as many as 5 odors. Thus, the presence of olfactory input and a highly discriminative ability for odors were found in the lateral hypothalamic area (LHA). Neuronal responses to the same odors were also studied in the septum (Spt). In anesthetized old world monkeys, evoked potentials were recorded in the LHA and in areas of the Spt and the nucleus accumbens (Acc) during stimulation of the olfactory bulb (OB). When the Spt (and probably the Acc with it) was subsequently destroyed, OB-evoked potentials in the LHA disappeared. Next, by injecting horseradish peroxidase (HRP) into the LHA, an olfactory pathway to the LHA was examined. Labeled neurons were found mainly in the Spt and the Acc, and only partly in other areas. However, labeled neurons were scarcely found in the prepyriform (PPF)-entorhinal (ER) area or in the olfactory tubercle (OT). The present study thus shows that an olfactory pathway to the LHA passes through the Spt and probably also the Acc, but not through the PPF-ER areas nor through the OT in the old world monkey.

Animals↗

Modulation by prostaglandin D2 of mitral cell responses to odor stimulation in rabbit olfactory bulb.

Recent work in our laboratory has demonstrated that prostaglandin (PG) D2 and the enzyme activities for its biosynthesis and inactivation are highly concentrated in the olfactory bulb and that the mitral cell layer of the bulb is enriched with PGD2-binding protein. We therefore investigated the role of PGD2 in the processing of odor signals in the rabbit olfactory bulb by an electrophysiological technique. Iontophoretic (-100 nA, 20 s), intra-arterial (0.0125-0.1 mg/kg) and intravenous (i.v., 0.05-0.3 mg/kg) administration of PGD2 enhanced and prolonged the responses of mitral cells to some of the olfactory stimuli tested. The extent and duration of granule cell inhibition of mitral cells were assessed by recording field potential responses in the bulb to paired lateral olfactory tract volleys. The i.v. administration of indomethacin or diclophenac, both of which are inhibitors of PG biosynthesis, resulted in prolongation of the granule cell inhibition of mitral cells without any significant change of the conditioning amplitudes. It also caused the reduction of the spike responses of mitral cells to olfactory stimuli. After treatment with indomethacin, the i.v. administration of PGD2 (1 mg/kg) rapidly reduced the duration of the granule cell inhibition of mitral cells. These results indicate that PGD2 plays a modulatory role in the mitral cell responses to odor stimuli by suppressing the inhibitory synaptic inputs from granule cells to mitral cells.

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Studies on the olfactory nervous system of the Old World monkey.

From the results of our electrophysiological and HRP studies in the old world monkey, multiple olfactory pathways have been clarified. The old world monkey has two neocortical olfactory areas, but no functional vomeronasal system. The response patterns to odors in various olfactory areas have also been studied. On the other hand, in the rabbit (Onoda and Iino, 1980) and dog (Onoda et al., 1981, 1982), which do have active vomeronasal systems, only one neocortical olfactory area was found. This important difference had already been indicated in three previous papers in which Takagi (1979, 1980, 1981) theorized that mammals can be divided into two groups according to their olfactory nervous mechanisms. One group includes old world monkeys, higher primates and man, and the other new world monkeys and lower mammals.

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An HRP study of neural pathways to neocortical olfactory areas in monkeys.

Afferent fiber projections to the two orbitofrontal olfactory areas of monkeys were studied using the horseradish peroxidase (HRP) technique. After injections of HRP into the lateroposterior (LPOF) or centroposterior (CPOF) area of the orbitofrontal cortex, some differences were found in the distribution of labeled cells between the projections to the LPOF and CPOF. These results, along with those of previous electrophysiological investigations, suggest the following conclusions: (1) the extrathalamic olfactory pathway to the LPOF identified by Tanabe et al. has relay neurons primarily in the substantia innominata and the amygdala and, secondarily, in the prorhinal cortex and the hypothalamus; (2) direct fibers to the LPOF from the amygdala and the prorhinal cortex pass through the areas ventral to the thalamus; (3) the transthalamic olfactory pathway to the CPOF identified by Yarita et al. has relay neurons concentrated primarily in the magnocellular portion of the mediodorsal nucleus of the thalamus.

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Odor response characteristics of thalamic mediodorsal nucleus neurons in the rabbit.

Extracellular responses were recorded from neurons in the thalamic mediodorsal nucleus (MD) of the lightly anesthetized rabbit. Eighty-seven neurons responded to electrical stimulation of the lateral olfactory tract (LOT shocks). They were located in the medial portion of the MD. In the same portion, negative field potentials with a short latency were evoked by the electrical stimulation of the olfactory projection area in the neocortex (OPA shocks). Fifty-nine MD neurons responded both to LOT and to OPA shocks. Among them, 17 thalamocortical relay neurons (which responded antidromically to OPA shocks) were found to respond transsynaptically to LOT shocks. Of the 87 LOT-responsive MD neurons, 48 responded to the odors applied. Eight odor-sensitive neurons were found to be the thalamocortical relay neurons. Thus, it was proven for the first time that a portion of the olfactory input to the OPA is mediated via relay neurons in the MD. Characteristics of response of MD neurons to odor stimulation were compared with those of OPA neurons. MD neurons did not show a selectivity of response to odors of urine, feces, or dry food pellets, to which OPA neurons responded exclusively. These results were discussed in relation to the functional role of the MD-OPA projection system in the discrimination of specific odors.

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The olfactory nervous system of the old world monkey.

This paper reviews work on olfactory function performed in the author's laboratory over the last 10 years. The following aspects of this work are covered. Neocortical olfactory areas were studied in old world monkeys. Olfactory responses were found in the lateroposterior and centroposterior portions of the orbitofrontal cortex (LPOF and CPOF). The routes of the olfactory nerve pathways to the LPOF and the CPOF were examined. An olfactory pathway to the lateral hypothalamic area (LHA) was also studied. Using unanesthetized monkeys, information processing of odors was studied in the OB, PPF-MA, LPOF, MDmc, CPOF, and LHA. In the LPOF and LHA, half or more of the cells responded differentially to one odor. We have thus been able to clearly demonstrate discrimination of odors at the cell level in these areas.

Anesthesia, General↗

Monosynaptic and disynaptic activation of pyriform cortex neurons by synchronous lateral olfactory tract volleys in the rabbit.

To elucidate the organization of synaptic inputs to pyriform cortex neurons, intracellular and extracellular responses of single units were analyzed in urethane-anesthetized rabbits. The lateral olfactory tract (LOT) or the olfactory bulb (OB) was electrically stimulated. Intracellular recordings revealed two types of cells (type I and type II cells), according to the types of EPSP evoked by the LOT or OB shock. The EPSP in the type I cells had shorter latencies (0.0 to 0.9 ms) from the onset of the component 2 (C2) wave of the field potential (which signals the onset of the synaptic depolarization of the apical dendrites of the pyramidal cells in the PC), and that in the type II cells had longer latencies (1.0 to 6.0 ms). A conditioning LOT or OB shock did not suppress the testing EPSP in the type I cells, whereas the conditioning stimulation greatly suppressed the testing EPSP in most of the type II cells. Extracellular recordings from units responding synaptically to the LOT or OB shock revealed a group of units which had short latencies (0.7 to 1.9 ms) of spike discharges. Those units, which were likely to be the same cells as the type I cells, are believed to mediate excitatory synaptic inputs to the type II cells. On the basis of these results, we concluded that type I cells are monosynaptically activated by LOT volleys, whereas type II cells are activated di- or polysynaptically by way of a relay from type I cells. The type I cells were recorded in both the superficial and the deep parts of the pyriform cortex, although they were recorded more frequently in the superficial part. On the other hand, most of the type II cells were recorded in the deep part of the PC. These results support and extend the previous model, in which the monosynaptically activated superficial pyramidal cells give rise to excitatory inputs to other pyramidal cells and neurons in deep layers.

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Neuronal pathways for activation of inhibitory interneurons in pyriform cortex of the rabbit.

The neuronal pathways responsible for the fast inhibitory postsynaptic potentials (IPSPs) elicited in principal cells in the pyriform cortex (PC) by volleys from the olfactory bulb (OB), the lateral olfactory tract (LOT), the anterior commissure (AC), and the deep-lying structures of the PC (DPC) were studied in the rabbit. The central latencies of the fast IPSPs (measured from the onset of the monosynaptic excitatory postsynaptic potential (EPSP) elicited by volleys through the LOT) ranged between 3.0 and 9.3 ms (5.5 +/- 1.3 (SD) ms; n = 54) in the case of OB shocks and between 4.5 and 6.5 ms (5.1 +/- 0.7 (SD) ms; n = 7) in the case of LOT shocks. The onset latencies of the fast IPSPs were between 2.5 and 11.8 ms (5.1 +/- 1.8 (SD) ms; n = 66) in the case of DPC shocks and between 3.5 and 10.1 ms (5.8 +/- 1.5 (SD) ms; n = 61) in the case of AC shocks. The conditioning OB or LOT shocks almost completely eliminated the LOT-evoked fast IPSP when the testing shock was applied at the peak period of the conditioning slow IPSP. The conditioning OB shocks also eliminated the initial part of the OB-evoked fast IPSP, leaving the later part of the fast IPSP almost unchanged. Thus, the onset latency of the OB-evoked fast IPSP was lengthened by 7.1 +/- 2.9 (SD) ms (n = 35) by the conditioning OB shock. The conditioning OB or DPC shocks left the peak amplitude of the DPC-evoked fast IPSP almost unaffected. Similarly, the conditioning OB or AC shocks left the peak amplitude of the AC-evoked fast IPSP almost unaffected. The conditioning OB, DPC, or AC shocks had only a slight influence on the onset latency of the DPC- or AC-evoked fast IPSPs. Rhythmical steps at intervals of 3-5 ms were observed in the rising phase of the OB-evoked fast IPSP. This was interpreted as a result of a repetitive impingement of interneuronal discharges on the impaled cells. Spatial facilitation was observed among the fast IPSPs evoked by volleys from the OB, DPC, and AC when shocks were applied at suitable intervals. A slight facilitation was also seen between the LOT-evoked fast IPSP and the DPC- or AC-evoked fast IPSP. These results were interpreted as a result of the convergence of excitatory synaptic inputs onto the presumed inhibitory interneurons from the four structures of the brain. A temporal facilitation of the fast IPSPs was observed when the OB, DPC, or AC shocks were applied repetitively at short intervals. This suggests a temporal facilitation of the spike discharges of the presumed inhibitory interneurons under similar conditions. From these results, criteria were determined for identifying the inhibitory interneurons.

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Interneurons mediating fast postsynaptic inhibition in pyriform cortex of the rabbit.

Interneurons mediating the fast IPSPs in principal cells in the pyriform cortex (PC) of the rabbit were searched for using criteria derived from the analysis of the properties of the fast inhibitory postsynaptic potentials (IPSPs). Thirty units were identified as inhibitory interneurons. The interneurons were activated synaptically by volleys from the olfactory bulb (OB), the lateral olfactory tract (LOT), the anterior commissure (AC), and deep-lying structures of the PC (DPC). The interneurons showed a tendency to discharge repetitively in response to shocks applied to these structures of the basal forebrain (OB, LOT, AC, and DPC). The conditioning OB shocks eliminated the testing LOT-evoked discharges of the interneurons. The conditioning OB shocks eliminated the initial part of the testing OB-evoked discharges, leaving the later part relatively unchanged. On the other hand, the conditioning OB shocks did not completely eliminate the testing DPC- or AC-evoked discharges. A temporal facilitation of discharges in the interneurons was observed in response to volleys from the OB, DPC, or AC. A spatial facilitation of discharges in the interneurons was observed in response to a combination of shocks applied to the OB, DPC, and AC. The interneurons were recorded at depths 525-2,755 microns deep to the turnover point of the component 2 wave of field potentials evoked by volleys through the LOT fibers. They were located mostly in the deeper part of layer III of the PC. Intracellular recordings from the presumed inhibitory interneurons showed that OB stimulation elicited two successive excitatory postsynaptic potentials (EPSPs) on which the bursting discharges were superimposed. These EPSPs were followed by a long-lasting hyperpolarizing potential. A comparison of the latencies of the antidromic activation of the principal cells and the synaptic activation of the inhibitory interneurons following OB or DPC stimulation suggested that the inhibitory interneurons are activated at least partly through the axon collaterals of the principal cells, which project their main axons to the OB or DPC. A circuit diagram was proposed for the neuronal pathways responsible for the fast IPSPs of principal cells in the PC.

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A transthalamic olfactory pathway to orbitofrontal cortex in the monkey.

1. Evoked potentials restricted to the magnocellular portion of the mediodorsal nucleus (MDmc) of the thalamus were recorded after stimulation of the olfactory bulb (OB) and the posterior orbital cortex of the frontal lobe (OFC). Potentials evoked by stimulation of OB were probably trans-synaptically elicited, while potentials evoked by stimulation of OFC were probably a result of antidromic activation. 2. The area in which stimulation could elicit antidromic evoked potentials in MDmc was located in the centroposterior portion of OFC (CPOF). This area corresponds approximately to Walker's (80) area 13 and to von Bonin and Bailey's (9) area FF, and is situated medial and just anterior to a previously identified olfactory area, the lateroposterior portion of OFC (LPOF), which receives olfactory impulses through the hypothalamus. 3. Using extracellular microelectrodes, 58 neurons that responded with short latencies to OFC stimulation were identified in MDmc. To determine whether these neurons were activated antidromically by CPOF stimulation, three conventional neurophysiological criteria were applied; 20 of 58 neurons satisfied all the three criteria. Hence, they were concluded to be thalamocortical relay (TCR) neurons. 4. Intracellular recording of MDmc neurons disclosed that CPOF stimulation elicits an antidromic spike potential accompanied by an afterhyperpolarization. This hyperpolarization was presumed to be due to concurrent stimulation of inhibitory orbitothalamic fibers. It was also shown that EPSP-like depolarizations with superimposed spike potentials often occurred in the middle of the afterhyperpolarization. 5. Intracellular recording of MDmc neurons strongly suggested that the remaining 38 neurons that did not satisfy one of the three criteria were also TCR neurons. 6. These studies provide electrophysiological evidence for a transthalamic olfactory pathway from OB through MDmc to CPOF. 7. Using an extracellular recording technique, responses of neurons to eight odors were examined in CPOF and MDmc of unanesthetized awake monkeys. When these results were compared with the responses of neurons to the same odors in OB, prepyriform-amygdaloid area, and LPOF, it was concluded that the newly found transthalamic olfactory pathway to CPOF is very different in function from the previously demonstrated transhypothalamic olfactory pathway to LPOF.

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Centrifugal influence on olfactory bulb activity in the rabbit.

(1) Regions which exert centrifugal influences on the olfactory bulb activity were studied by applying systematic stimulation to various areas of the ipsilateral telencephalon in the rabbit. By delivering electric stimuli to the anterior commissure (AC), the deep lying structures in the projection areas of the lateral olfactory tract (LOT) and the medial forebrain bundle situated between the lateral hypothalamic area and the lateral preoptic area, negative field potentials were evoked in the granule cell layer (GCL) of the bulb. (2) Intracellular recordings from the mitral cells and the GCL neurons in the olfactory bulb were performed in order to clarify the modes of the centrifugal influences on the olfactory bulb neurons. (3) EPSPs were recorded in the GCL neurons by stimulation of the deep-lying structure of the prepiriform cortex as well as by stimulation of the AC. The onset time and duration of the EPSPs corresponded well to those of the negative field potentials in the GCL. Thus, it was suggested that these negative potentials were caused by the EPSPs of the number of granule cells. (4) In almost all of the mitral cells, IPSPs were recorded by stimulation of the AC and the deep-lying structures of the LOT projection areas. The onsets of the IPSPs were found with delays of several milliseconds from those of the negative field potentials in the GCL. (5) It was postulated that the excitation of the centrifugal system mainly exerts a depressive influence on the activity of the mitral cell, and that the GCL neuron (presumably the granule cell) seems to be an inhibitory interneuron interpolated between the extrinsic fibers from the telencephalon and the mitral cell.

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An intracellular study of dendrodendritic inhibitory synapses on mitral cells in the rabbit olfactory bulb.

1. In the rabbit olfactory bulb, intracellular potentials were recorded from mitral cells and from neurones in the granule cell layer (g.c.l.) following lateral olfactory tract (l.o.t.) stimulation. 2. Most recordings from mitral cells showed large (5-21 mV) and prolonged (60-650 msec) i.p.s.p.s subseuqent to the antidromic spikes. These i.p.s.p.s decreased in amplitude and then reversed in polarity by progressive increase in hyperpolarizing current applied intracellularly. They were accompanied by a prominent and long lasting (up to 100 msec) conductance increase of the mitral cell membrane. 3. Reversed i.p.s.p.s of mitral cells having quite different time courses from the original hyperpolarizing i.p.s.p.s suggest that the inhibitory synapses are widely distributed on the soma and dendrites. 4. E.p.s.p.s could be recorded from g.c.l. cells whose onset latency was approximately 0.6 msec shorter than that of mitral cell i.p.s.p.s. Comparison of the behaviour of e.p.s.p.s in g.c.l. cells and that of mitral cell i.p.s.p. under various conditions of l.o.t. stimulation suggests that these g.c.l. cells are the inhibitory interneurones mediating mitral cell inhibition. 5. The results support the hypothesis of dendrodentritic pathways for activation of granule cells and subsequent inhibition of mitral cells.

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