Biomedical subjects

Fu-Sun Lo

Publications and source records attributed to Fu-Sun Lo.

7 recordsLinked to original sources

PubMed2005

NMDA receptor-dependent regulation of axonal and dendritic branching.

In the rodent trigeminal principal nucleus (PrV), trigeminal afferent terminals and postsynaptic cells form discrete modules ("barrelettes") that replicate the patterned array of whiskers and sinus hairs on the snout. Barrelette neurons of the PrV relay whisker-specific patterns to the contralateral thalamus and, subsequently, to the primary somatosensory barrel cortex. Genetic impairment of NMDA receptor (NMDAR) function blocks development of barrelettes in the PrV. Underlying cellular and functional defects are not known. Here, we examined morphological differentiation of whisker afferents, dendritic differentiation of barrelette cells, and their electrophysiological properties in mice with genetic perturbations of the essential subunit NR1 of NMDARs. We show that in NR1 gene knock-down (KD) and knock-out mice, whisker afferents begin their embryonic development normally but, over time, fail to segregate into patches, and instead they develop exuberant terminal arbors spanning most of the PrV. Postnatal NR1KD barrelette cells, with significantly reduced NMDA currents, retain their membrane and synaptic properties but develop longer dendrites with no orientation preference. These results indicate that NMDARs regulate growth of presynaptic terminal arbors and postsynaptic dendritic branching, thereby leading to consolidation of synapses and patterning of presynaptic and postsynaptic elements.

Animals↗

PubMed2003

Nature of inhibitory postsynaptic activity in developing relay cells of the lateral geniculate nucleus.

Using intracellular recordings in an isolated (in vitro) brain stem preparation, we examined the inhibitory postsynaptic responses of developing neurons in the dorsal lateral geniculate nucleus (LGN) of the rat. As early as postnatal day (P) 1-2, 31% of all excitatory postsynaptic (EPSP) activity evoked by electrical stimulation of the optic tract was followed by inhibitory postsynaptic potentials (IPSPs). By P5, 98% of all retinally evoked EPSPs were followed by IPSP activity. During the first postnatal week, IPSPs were mediated largely by GABA(A) receptors. Additional GABA(B)-mediated IPSPs emerged at P3-4 but were not prevalent until after the first postnatal week. Experiments involving the separate stimulation of each optic nerve indicated that developing LGN cells were binocularly innervated. At P11-14, it was common to evoke EPSP/IPSP pairs by stimulating either the contralateral or ipsilateral optic nerve. During the third postnatal week, binocular excitatory responses were encountered far less frequently. However, a number of cells still maintained a binocular inhibitory response. These results provide insight about the ontogeny and nature of postsynaptic inhibitory activity in the LGN during the period of retinogeniculate axon segregation.

Animals↗

PubMed2002

Properties of LTD and LTP of retinocollicular synaptic transmission in the developing rat superior colliculus.

The developing retinocollicular pathway undergoes synaptic refinement in order to form the precise retinotopic pattern seen in adults. To study the mechanisms which underlie refinement, we investigated long-term changes in retinocollicular transmission in rats aged P0-P25. Field potentials (FPs) in the superior colliculus (SC) were evoked by stimulation of optic tract fibers in an in vitro isolated brainstem preparation. High intensity stimulation induced long-term depression (LTD) in the SC after both low (1000 stimuli at 1 Hz) and higher (1000 stimuli at 50 Hz) frequency stimulation. The induction of LTD was independent of activation of NMDA and GABA(A) receptors, because D-APV (100 microM) and bicuculline (10 microM) did not block LTD. Induction of LTD was dependent upon activation of L-type Ca(2+) channels as 10 microM nitrendipine, an L-type Ca(2+) channel blocker, significantly decreased the magnitude of LTD. LTD was down-regulated during development. LTD magnitude was greatest in rats aged P0-P9 and significantly less in rats aged P10-P25. Long-term potentiation (LTP) was induced by low intensity stimulation and only after high frequency tetanus (1000 stimuli at 50 Hz). LTP was NMDA receptor dependent because d-APV (100 microM) completely abolished it. LTP induction was also blocked by the L-type Ca2+ channel blocker nitrendipine. The magnitude of LTP first increased with age, being significantly greater at P7-P13 than at P0-3 and then decreased at P23-25. In summary, both LTD and LTP are present during retinocollicular pathway refinement, but have different transmitter and ionic mechanisms and time courses of expression.

Action Potentials↗

PubMed2002

Synaptic mechanisms regulating the activation of a Ca(2+)-mediated plateau potential in developing relay cells of the LGN.

Using intracellular recordings in an isolated (in vitro) rat brain stem preparation, we examined the synaptic responses of developing relay neurons in the dorsal lateral geniculate nucleus (LGN). In newborn rats, strong stimulation of the optic tract (OT) evoked excitatory postsynaptic potentials (EPSPs) that gave rise to a sustained (300-1,300 ms), slow-decaying (<0.01 mV/s), depolarization (25-40 mV). Riding atop this response was a train of spikes of variable amplitude. We refer to this synaptically evoked event as a plateau potential. Pharmacology experiments indicate the plateau potential was mediated by the activation of high-threshold L-type Ca(2+) channels. Synaptic activation of the plateau potential relied on N-methyl-D-aspartate (NMDA) receptor-mediated activity and the spatial and/or temporal summation of retinally evoked EPSPs. Inhibitory postsynaptic responses (IPSPs) did not prevent the expression of the plateau potential. However, GABA(A) receptor activity modulated the intensity of optic tract stimulation needed to evoke the plateau potential, while GABA(B) receptor activity affected its duration. Expression of the plateau potential was developmentally regulated, showing a much higher incidence at P1-2 (90%) than at P19-20 (1%). This was in part due to the fact that developing relay cells show a greater degree of spatial summation than their mature counterparts, receiving input from as many as 7-12 retinal ganglion cells. Early spontaneous retinal activity is also likely to trigger the plateau potential. Repetitive stimulation of optic tract in a manner that approximated the high-frequency discharge of retinal ganglion cells led to a massive temporal summation of EPSPs and the activation of a sustained depolarization (>1 min) that was blocked by L-type Ca(2+) channel antagonists. These age-related changes in Ca(2+) signaling may contribute to the activity-dependent refinement of retinogeniculate connections.

2-Amino-5-phosphonovalerate↗

PubMed2002

L-type calcium channel-mediated plateau potentials in barrelette cells during structural plasticity.

Development and maintenance of whisker-specific patterns along the rodent trigeminal pathway depends on an intact sensory periphery during the sensitive/critical period in development. Barrelette cells of the brain stem trigeminal nuclei are the first set of neurons to develop whisker-specific patterns. Those in the principal sensory nucleus (PrV) relay these patterns to the ventrobasal thalamus, and consequently, to the somatosensory cortex. Thus PrV barrelette cells are among the first group of central neurons susceptible to the effects of peripheral damage. Previously we showed that membrane properties of barrelette cells are distinct as early as postnatal day 1 (PND 1) and remain unchanged following peripheral denervation in newborn rat pups (Lo and Erzurumlu 2001). In the present study, we investigated the changes in synaptic transmission. In barrelette cells of normal PND 1 rats, weak stimulation of the trigeminal tract (TrV) that was subthreshold for inducing Na(+) spikes evoked an excitatory postsynaptic potential-inhibitory postsynaptic potential (EPSP-IPSP) sequence that was similar to the responses seen in older rats (Lo et al. 1999). Infraorbital nerve transection at birth did not alter excitatory and inhibitory synaptic connections of the barrelette cells. These observations suggested that local neuronal circuits are already established in PrV at birth and remain intact after deafferentation. Strong stimulation of the TrV induced a sustained depolarization (plateau potential) in denervated but not in normal barrelette neurons. The plateau potential was distinct from the EPSP-IPSP sequence by 1) a sustained (>80 ms) depolarization above -40 mV; 2) a slow decline slope (<0.1 mV/ms); 3) partially or totally inactivated Na(+) spikes on the plateau; and 4) a termination by a steep decay (>1 mV/ms) to a hyperpolarizing membrane level. The plateau potential was mediated by L-type Ca(2+) channels and triggered by a N-methyl-D-aspartate (NMDA) receptor-mediated EPSP. gamma-aminobutyric acid-A (GABA(A)) receptor-mediated IPSP dynamically regulated the latency and duration of the plateau potential. These results indicate that after neonatal peripheral damage, central trigeminal inputs cause a large and long-lasting Ca(2+) influx through L-type Ca(2+) channels in barrelette neurons. Increased Ca(2+) entry may play a key role in injury-induced structural remodeling, and/or transsynaptic cell death.

Action Potentials↗

PubMed1989

Dependence of Retinogeniculate Transmission on Membrane Voltage in the Cat.

The mammalian lateral geniculate nucleus seems organized to gate or control the gain of retinogeniculate transmission, the result of which is then relayed to the visual cortex. We have performed in vivo intracellular studies of retinogeniculate transmission along these retino-geniculo-cortical pathways in cats by recording the retinally evoked excitatory postsynaptic potential (EPSP) in geniculate neurons. In cats, these pathways are organized into two parallel and functionally distinct channels, the X and Y pathways. We found that nearly all geniculate X cells display a fairly conventional voltage dependency for their retinally evoked EPSPs, because the amplitudes of these EPSPs decrease fairly linearly with membrane depolarization as the EPSP reversal potential is approached. Rare X cells and all Y cells, however, show an unconventional response: over a wide range of membrane potentials, their EPSP amplitudes increase with membrane depolarization. This increase does not result from alterations in neuronal input resistance and instead seems due to changes in synaptic conductance. The underlying cause of this voltage dependency remains to be determined. None the less, it does afford an interesting means by which retinogeniculate transmission can be gated, since non-retinal inputs (e.g. corticogeniculate axons) that can control a relay Y cell's membrane potential can also modulate the cell's EPSP amplitude.

Journal Article↗

PubMedDate not supplied

Structural and functional composition of the developing retinogeniculate pathway in the mouse.

The advent of transgenic mice has made the developing retinogeniculate pathway a model system for targeting potential mechanisms that underlie the refinement of sensory connections. However, a detailed characterization of the form and function of this pathway is lacking. Here we use a variety of anatomical and electrophysiological techniques to delineate the structural and functional changes occurring in the lateral geniculate nucleus (LGN) of dorsal thalamus of the C57/BL6 mouse. During the first two postnatal weeks there is an age-related recession in the amount of terminal space occupied by retinal axons arising from the two eyes. During the first postnatal week, crossed and uncrossed axons show substantial overlap throughout most of the LGN. Between the first and second week retinal arbors show significant pruning, so that by the time of natural eye opening (P12-14) segregation is complete and retinal projections are organized into distinct eye-specific domains. During this time of rapid anatomical rearrangement, LGN cells could be readily distinguished using immunocytochemical markers that stain for NMDA receptors, GABA receptors, L-type Ca2+ channels, and the neurofilament protein SMI-32. Moreover, the membrane properties and synaptic responses of developing LGN cells are remarkably stable and resemble those of mature neurons. However, there are some notable developmental changes in synaptic connectivity. At early ages, LGN cells are binocularly responsive and receive input from as many as 11 different retinal ganglion cells. Optic tract stimulation also evokes plateau-like depolarizations that are mediated by the activation of L-type Ca2+ channels. As retinal inputs from the two eyes segregate into nonoverlapping territories, there is a loss of binocular responsiveness, a decrease in retinal convergence, and a reduction in the incidence of plateau potentials. These data serve as a working framework for the assessment of phenotypes of genetically altered strains as well as provide some insight as to the molecular mechanisms underlying the refinement of retinogeniculate connections.

Aging↗