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F S Lo

Publications and source records attributed to F S Lo.

At least 37 records · Page 2Linked to original sources

Functional connectivity in the rodent trigeminal pathway grown in vitro.

In explant cocultures of the rat trigeminal pathway, embryonic trigeminal ganglion cells grow their axons into peripheral cutaneous and central nervous system targets (R.S. Erzurumlu, S. Jhaveri, Target influences on the morphology of trigeminal axons, Exp. Neurol, 135 (1995) 1-16; R.S. Erzurumlu, S. Jhaveri, H. Takahashi, R.D.G. McKay, Target-derived influences on axon growth modes in explant cocultures of trigeminal neurons, Proc. Natl. Acad. Sci. USA 90 (1993) 7235-7239). In heterochronic cocultures, composed of embryonic trigeminal ganglion, embryonic whisker pad and postnatal brainstem slice, trigeminal axons develop arbors and terminal boutons in the brainstem trigeminal nuclei. To determine whether these terminal arbors establish functional connections with the brainstem neurons, we examined the electrophysiological properties of brainstem neurons and their responsiveness to trigeminal ganglion stimulation. Intracellular recordings were done in vitro on cells of the trigeminal subnucleus interpolaris (SPI) in trigeminal pathway cocultures (E15 whisker pad, E15 trigeminal ganglion, and postnatal day (PND) 0-2 brainstem slice) or in the SPI of acutely prepared brainstem slices. Electrophysiological properties of SPI cells in both preparations were virtually identical. The voltage responses of SPI neurons to intracellular current injection were highly linear suggesting they lacked a number of voltage-dependent conductances. Depolarizing current injection produced trains of action potentials with a frequency that varied with stimulus intensity. In explant cocultures, electrical activation of the trigeminal ganglion evoked EPSPs, and EPSPs coupled with IPSPs in SPI cells. Bicuculline blockade of IPSP activity resulted in long lasting EPSPs whose duration increased with membrane depolarization. These results show that brainstem trigeminal neurons can retain their functional properties in culture and establish functional connections with primary sensory afferents.

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An in vitro model of the kitten retinogeniculate pathway.

An organotypic explant coculture method is described for the developing retinogeniculate pathway of the cat. Retinal explants and thalamic slices containing the dorsal lateral geniculate nucleus (LGN), derived from early postnatal kittens, can be grown in serum-free culture medium for several days. In such cultures, retinal ganglion cells (RGCs) and LGN neurons retained their age-specific morphological features and developed functional connections. Labeling of RGCs and their processes with DiI showed that all three major classes of RGCs (alpha/Y, beta/X, gamma/W) were present in cocultured retinal explants. Retinal axons readily regenerated into thalamic slices and, over time, developed arbors within the LGN. Retrograde labeling from the LGN traced the origin of these axons almost exclusively to alpha-cells in the retina. In vitro intracellular recordings indicated that LGN cells maintained their basic electrophysiological properties in coculture. Current injection generated action potentials, and, at hyperpolarized levels, it led to low-threshold Ca2+ spiking. Regenerated retinal axons also formed functional connections with LGN neurons. Electrical stimulation of the retinal explant elicited excitatory postsynaptic responses (EPSPs) in LGN cells. Drop application of specific glutamate antagonists indicated that EPSPs had both N-methyl-D-aspartate (NMDA) and non-NMDA receptor components. The morphology of the LGN neurons was examined after intracellular injections of biocytin during recording. Labeled cells were very similar to those of early postnatal kittens. Although, in general, they had relatively small soma and simple dendritic branching patterns, a few could be recognized as X- or Y-cells. Thus the coculture model can be used to assay the regenerative propensity of different types of RGCs during development.

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Recurrent inhibitory interneurons of the Rabbit's lateral posterior-pulvinar complex.

We recorded from 118 neurons in the visual sector of the thalamic reticular nucleus (TRN) in anesthetized rabbits. Cells were identified by their location and characteristic burst responses to stimulation of the primary visual cortex (Cx) and optic chiasm (OX) and were classified into two groups. Type I cells had relatively short latencies from both OX and Cx stimulation, and the latency from OX was always longer than from Cx. In contrast, type II cells had much longer latencies after OX and Cx stimulation, and the latency from OX was always shorter than from Cx. Type I cells were located in the dorsal part of TRN, whereas type II cells were located in the ventral part of TRN. The physiological properties and location of type I TRN cells indicate that they are recurrent inhibitory interneurons of the dorsal lateral geniculate nucleus (LGN). Type II TRN cells most likely function as recurrent inhibitory interneurons for the lateral posterior nucleus-pulvinar complex (LP) because they could be activated antidromically by LP stimulation and orthodromically activated via axonal collaterals of LP cells. Type II TRN cells exhibited a prolonged depression after Cx or OX stimulation. Intracellular recordings showed that a prolonged inhibitory postsynaptic potential was evoked by Cx or OX stimulation. Therefore, these recurrent interneurons of LP, type II cells form mutual inhibitory connections just like those recurrent interneurons of LGN, type I cells. Our data suggest that the geniculocortical and extrageniculate visual pathways have similar recurrent inhibitory circuits.

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[Acetylcholine decreases low threshold T-type calcium conductance of relay cells in the cat's lateral geniculate nucleus].

The effect of acetylcholine (ACh) on the low threshold T-type Ca2+ conductance of relay cells in the cat lateral geniculate nucleus (LGN) was studied using in vitro thalamic slices. Results from both current-clamp and voltage-clamp experiments showed that the low threshold Ca2+ conductance was inhibited by ACh in most (82%) of the LGN neurons tested, even when the membrane potential was clamped to the control level. This inhibitory effect was independent of the changes in membrane potential by ACh. Therefore, ACh might exert a direct action on low threshold Ca2+ channels.

Acetylcholine↗

Time course of inhibition induced by a putative saccadic suppression circuit in the dorsal lateral geniculate nucleus of the rabbit.

Psychological studies have revealed that a visual suppression occurs during the saccadic eye movements to maintain the stable visual image. This visual suppression is named saccadic suppression. A typical saccadic suppression precedes the saccadic eye movements by 30-60 ms, lasts 120-180 ms, and is followed by a 100-150 ms facilitation. Recently, we have revealed an inhibitory circuit connecting the deep layers of the superior colliculus (SC) to the dorsal lateral geniculate nucleus (LGN), via the central lateral nucleus in the thalamus (CL) and thalamic reticular nucleus (TRN). We speculated that this inhibitory circuit might mediate saccadic suppression in the rabbit. In the present study, we used intracellular recording technique to further examine the synaptic and intrinsic responses of CL cells, TRN cells, and LGN cells to the activation of this inhibitory circuit. We found that the stimulation of the deeper layers of the SC induced a fast excitation post-synaptic potential (EPSP) in CL cells, followed by a robust EPSP in TRN cells and a prolonged inhibitory postsynaptic potential (IPSP) in LGN cells. The EPSP in TRN cells was always followed by a small inhibitory postsynaptic potential (IPSP). The IPSP in LGN cells lasted about 133 +/- 27 ms. Sometimes, a rebound bursting occurred after the IPSP in LGN cells. We also examined whether activation of this inhibitory circuit could suppress the retino-geniculo-cortical pathway. We found that the SC stimulation always suppressed the evoked potential in the visual cortex induced by the stimulation of the optic chiasm. Our results of the inhibitory circuit can induce an inhibition in the LGN and a suppression on the retino-geniculo-cortical pathway. The time courses of the inhibition and suppression were compatible with that of saccadic suppression revealed by psychological and physiological studies. These results support the idea that the inhibitory circuit of SC (deeper layers)-CL-TRN-LGN may mediate the saccadic suppression in the rabbit LGN.

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[Passive cable properties of relay cells in dorsal lateral geniculate nucleus of the rabbit].

We measured the passive membrane properties of 24 relay cells in slice preparation of the lateral geniculate nucleus of the rabbit. The resting membrane potential was -62.7 +/- 4.1 mV (mean +/- SD) with an input resistance of 30.4 +/- 11.2 M omega. According to Rall's linear cable model, the electrotonic length (L) of the dendrite was 0.79 +/- 0.13. The voltage attenuation factor (H) was 1.33 +/- 0.11. All these indicated that the relay cells were electrically compact. DC voltage on the distal dendrite could spread to the soma attenuated only by 25%.

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Physiological properties of the output neurons in the deep layers of the superior colliculus of the rabbit.

Using antidromic and orthodromic stimulation techniques, we studied physiological properties of the output neurons in the deep layers of the superior colliculus (SC) of 34 Now Zealand rabbits. SC cells antidromically activated from the contralateral predorsal bundle (PDB) could also be activated by stimulation of the contralateral SC and ipsilateral central lateral nucleus of the thalamus (CL). The majority of these output neurons responded predominantly to the stimulation of the optic nerve, and only a small proportion of the output neurons were responsive to the stimulation of somatosensory and auditory (and/or vestibular) nerves. These results suggest that the orienting reflex might be elicited mainly by visual afferents in the rabbit. The output SC neurons were subject to a 70 ms inhibition after antidromic stimulation of the PDB and a 40 ms inhibition after transsynaptic (orthodromic) stimulation of the optic chiasm (OX), indicating that the output neurons in the deep layers of the SC might be subject to at least two inhibitory circuits. These results are discussed in the context of a putative saccadic suppression circuitry model.

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Feedback inhibition in the cat's lateral geniculate nucleus.

Feedback inhibition is generally believed to be a ubiquitous feature of brain circuitry, but few specific instances have been documented. An example in cats is the supposed feedback circuit involving relay cells of the lateral geniculate nucleus and cells of the perigeniculate nucleus (a part of the thalamic reticular nucleus): geniculate relay cells innervate the perigeniculate nucleus, which, in turn, provides an inhibitory, GABAergic projection back to the lateral geniculate nucleus. However, feedback inhibition at the single-cell level requires that a given perigeniculate cell project back onto the same geniculate relay cell that innervates it. We probed for this in an in vitro slice preparation of the cat's lateral geniculate nucleus. We evoked a single action potential in a geniculate cell via a brief, depolarizing pulse delivered through an intracellular recording electrode and looked for any evoked hyperpolarizations. For 6 of the 36 geniculate cells tested, we observed a long-lasting hyperpolarization after the action potential, and much of this was eliminated by application of bicuculline, suggesting synaptically activated inhibitory postsynaptic potentials. We interpreted this to be clear evidence that a given neuron may inhibit itself via circuitry mediating feedback inhibition in the cat's lateral geniculate nucleus.

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Intracellular and extracellular in vivo recording of different response modes for relay cells of the cat's lateral geniculate nucleus.

Prior studies of thalamic neurons have demonstrated that they exhibit at least two response modes: a relay mode and a burst mode. During the relay mode, sensory information is faithfully relayed to cortex; during the burst mode, which is caused by a voltage-dependent Ca2+ conductance, this relay of sensory information is interrupted. We began in vivo studies of these response modes in neurons from the lateral geniculate nucleus of anesthetized, paralyzed cats. Each of the 9 X and 10 Y cells we recorded intracellularly displayed voltage-dependent, low threshold spikes that were presumably the Ca2+ spikes described from in vitro recording. These spikes were triangular in waveform and typically had 2-7 fast action potentials (interspike intervals of 1.2-4 ms) riding its crest. Furthermore, the cell's membrane had to be hyperpolarized to de-inactivate the low threshold spike before a depolarization could then activate it. We could activate these low threshold spikes in Y cells from EPSPs, whether spontaneous or evoked from activation of the optic chiasm. However, in only one of the X cells could we activate low threshold spikes from chiasm shock; in the remainder, we could activate low threshold spikes only via depolarizing current pulses, possibly because the EPSPs of these X cells were too small to activate these spikes. We also used extracellular recording to study spontaneous activity and responses to chiasm shock from 114 geniculate neurons and, as a control, 57 optic tract axons. We concentrated on periods of bursty responsiveness signifying the burst mode. We define a burst as 2-7 action potentials with interspike intervals less than or equal to 4 ms, and the bursts are separated by greater than 100 ms; from our intracellular recording, we know that such bursts signify low threshold spikes. We found that, during extracellular recording, 20 of the 39 X cells and each of the 75 Y cells displayed evidence of the burst response mode, although burst periods were rare in X cells. Electrical activation of the optic chiasm greatly enhanced the burstiness of Y cells for periods of 500 ms or more. We also electrically stimulated the parabrachial region of the midbrain, which provides a mostly cholinergic innervation to the lateral geniculate nucleus. Although parabrachial activation by itself had no detectable effect on Y cell response modes, prior parabrachial activation prevented the enhanced burstiness caused by chiasm stimulation. This parabrachial effect lasted for roughly 500 ms after stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

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In vivo recording of postsynaptic potentials and low threshold spikes in W cells of the cat's lateral geniculate nucleus.

We obtained good intracellular recording from 5 W cells in the C-laminae of the cat's lateral geniculate nucleus. The recordings were made from an anesthetized and paralyzed in vivo preparation. We found a consistent pattern for the postsynaptic potentials evoked from activation of the optic chiasm: first was an IPSP followed by an EPSP. This is very different from the pattern seen in X and Y cells, for which an EPSP always appears first and is then followed by an IPSP. We interpret the pattern for W cells as follows. The initial IPSP is disynaptic; this involves retinogeniculate conduction over very fast Y axons and a relay through an interneuron. The EPSP is monosynaptic, reflecting retinogeniculate conduction over very slow W axons. A possible implication for this is that activity over the Y pathway may generally inhibit geniculate W cells before these W cells can be excited by their retinal afferents. Finally, we elicited from each of these W cells voltage-dependent, low threshold spikes, which are very similar to those displayed by X and Y cells. These spikes can interrupt normal retinogeniculate transmission, and they are prevented by maintaining relatively depolarized membrane potentials.

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A study of neuronal circuitry mediating the saccadic suppression in the rabbit.

Stimulation of the deep layers of the superior colliculus (SC) evoked an IPSP in the relay cells of the lateral geniculate nucleus (LGN). The latency of the IPSP ranged from 3.3 to 4.7 ms with an average of 3.87 +/- 0.56 ms (S.D.). The IPSP from SC stimulation was proposed to be mediated by the recurrent inhibitory circuit to LGN, since the recurrent inhibitory interneurones in the thalamic reticular nucleus (R) responded to the same stimulation with a latency of 2.14 +/- 0.43 ms, which was 1.73 ms shorter than the latency of the IPSP in LGN relay cells. This was in good agreement with our previous observation that the recurrent interneurones always fired about 1.8 ms prior to the onset of the recurrent IPSP in LGN (Lo and Xie 1987b). The recurrent inhibitory interneurones could also be excited by stimulation of the central lateral nucleus (CL) with a very short latency (0.57 +/- 0.15 ms), suggesting a monosynaptic connection between the central lateral nucleus and the reticular recurrent interneurones. This suggestion was supported by the fact that CL neurones, which projected to the striate cortex (Cx), were antidromically excited by stimulation of the caudal part of R where the recurrent inhibitory interneurones were situated. CL neurone's response to stimulation of the deep layers of SC (SC-CL response) has a latency of 1.68 +/- 0.56 ms, which was comparable with the difference between the latency of SC-R response and that of CL-R response, just as expected from the notion that the saccadic suppression is mediated by a circuit of SC (deep layers) -CL-R-LGN.

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Location of interneurones in the recurrent inhibitory circuit of the rabbit lateral geniculate nucleus.

Injection of horseradish peroxidase (HRP) into the dorsal lateral geniculate nucleus (LGN) of the rabbit gave rise to retrograde labeling of neurones in the caudal part of the thalamic reticular nucleus. Electrophysiological observations demonstrated that these neurones met all criteria for interneurones in the recurrent inhibitory circuit of the geniculo-cortical pathway. They responded to stimulation of the visual cortex (Cx) or the optic chiasm (OX) with a burst of repetitive discharges, in agreement with the long-lasting IPSP from Cx or OX in relay cells of LGN. Results of collision test showed that the reticular neurones received excitatory input via axonal collaterals of relay cells. The latency of their response to stimulation of Cx or OX is about 1.8 ms shorter than that of the corresponding IPSP in the relay cells. Stimulation of LGN evoked an antidromic spike in reticular neurones with a latency of about 1.1 ms, indicating a monosynaptic projection from the latter to the relay cells. All evidence indicates that interneurones in the recurrent inhibitory circuit are most likely located in the caudal part of the thalamic reticular nucleus of the rabbit.

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Control of recurrent inhibition of the lateral geniculate nucleus by afferents from the superior colliculus of the rabbit: a possible mechanism of saccadic suppression.

Stimulation of the ipsilateral superior colliculus elicited a short burst of discharges of the recurrent inhibitory interneurones in the geniculocortical pathway of the rabbit. The most effective stimulating sites for this excitation were located in the deep layers rather than the superficial layers of the superior colliculus. The short latency of the response (2.3 +/- 0.6 ms) implied an oligo-synaptic excitatory pathway from the deep layers of the superior colliculus to the recurrent interneurones located in the caudal reticular nucleus of the thalamus. Following the excitation of the interneurone, there was a prolonged inhibition which started 10-30 ms and ended 150 ms after the collicular stimulation. The maximal inhibition occurred 50-70 ms after the stimulation. The effects of collicular stimulation on the recurrent inhibitory interneurones may be concerned with the inhibition of the visual pathway during saccades and with the disinhibition of "facilitation" during fixation of a new visual target.

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Interaction between inhibitory pathways to principal cells in the lateral geniculate nucleus of the cat.

Inhibitory interactions between interneurones of the lateral geniculate nucleus (LGN) of the cat were studied with an indirect method based on intracellular recordings of synaptic responses in principal cells. Recurrent inhibitory postsynaptic potentials (IPSPs), evoked by antidromic activation of principal cell axons in the visual cortex, were depressed by a preceding stimulation of the optic tract or the visual cortex. Disynaptic feed-forward IPSPs, evoked by optic tract stimulation, were likewise depressed after cortex stimulation. The duration of the depression was in both cases about 100 ms. The effect was not due to conductance changes in the recorded principal cells or to activation of cortico-geniculate fibres. The observations indicate that perigeniculate neurones, the recurrent inhibitory interneurones of the LGN, have mutual inhibitory connexions and that they also project to intrageniculate interneurones, the inhibitory cells in the feed-forward pathway to principal cells. These conclusions were supported by intracellular recordings from a few interneurones. No evidence was found for interaction between feed-forward interneurones activated from separate eyes or for a projection from intrageniculate interneurones to perigeniculate cells. The results point to an unexpected similarity in the organization of the recurrent inhibitory system of principal cells in the LGN and of spinal motoneurones. It is suggested that the recurrent system of the LGN serves as a variable gain regulator in analogy with a recently proposed model for the spinal system.

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Inhibition from the brain stem of inhibitory interneurones of the cat's dorsal lateral geniculate nucleus.

Brain-stem control of inhibitory circuits in the dorsal lateral geniculate nucleus (d.l.g.n.) of the cat was studied with extracellular recordings from functionally identified interneurones and with intracellular recordings from principal cells. Perigeniculate neurones, the recurrent inhibitory interneurones of the d.l.g.n., were inhibited by low-threshold stimulation within a wide bilateral field of the brainstem reticular formation extending from the rostral mesencephalon to the caudal medulla oblongata. The inhibition had a latency of 10-12 ms for stimulation sites in the mesencephalon and a duration of about 100 ms. The brain-stem stimulation evoked large hyperpolarizing potentials in intracellularly recorded perigeniculate neurones, indicating that the effect was due to post-synaptic inhibition. Intrageniculate interneurones, the feed-forward inhibitory interneurones of the d.l.g.n., were inhibited with a similar time course from the same region of the brain stem. Both feed-forward and recurrent inhibitory post-synaptic potentials (i.p.s.p.s) in principal cells were depressed by a preceding stimulation of brain-stem sites effective for the interneurones. The depression had about the same time course as the inhibition of the interneurones and it occurred without a concomitant change in the membrane potential of the recorded principal cells. A small depolarizing potential, with a latency of 10-20 ms, was observed in some principal cells after brain-stem stimulation. The potential reversed polarity when i.p.s.p.s were reversed by current injection into the recorded cell indicating that it was due to disinhibition of the principal cells. The possible neuronal pathway for the inhibition of the d.l.g.n. in interneurones is considered and it is proposed that the effect is mediated by a group of neurones located in the caudal mesencephalon and the rostral pons close to the fibres of the brachium conjunctivum.

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