Biomedical subjects

William Guido

Publications and source records attributed to William Guido.

8 recordsLinked to original sources

PubMed2006

Loss of binocular responses and reduced retinal convergence during the period of retinogeniculate axon segregation.

In the developing mammalian visual system, axon terminals from the two eyes overlap in the dorsal lateral geniculate nucleus (LGN) but then undergo a period of refinement and segregate to form distinct eye-specific domains. We report on the changes in synaptic transmission that occur in rodent LGN during the period of retinogeniculate axon segregation by using anterograde labeling techniques in conjunction with an in vitro preparation where large segments of each optic nerve are preserved. Anterograde labeling of retinal projections in early postnatal day (P) rats with cholera toxin beta subunit indicated an age-related recession in uncrossed retinal projections. Between P2 and P5 uncrossed projections occupied as much as 50% of the LGN and overlapped substantially with crossed projections. Between the first and second postnatal week uncrossed projections receded, so by P14 they assumed an adultlike profile occupying 15-20% of LGN and showed little or no overlap with crossed projections. The postsynaptic responses of LGN cells evoked by the separate stimulation of each optic nerve indicated that before P14, many relay cells were binocularly innervated and received at least four to six inputs from each eye. However, these features of retinogeniculate connectivity were transient and their attrition occurred in concert with a retraction of retinal arbors into nonoverlapping, eye-specific regions. By P18 cells were monocularly innervated and received input from one to three retinal ganglion cells. These results provide a better understanding of the underlying changes in synaptic circuitry that occur during the anatomical segregation of retinal inputs into eye-specific territories.

Animals↗

PubMed2006

Failure to maintain eye-specific segregation in nob, a mutant with abnormally patterned retinal activity.

Axon terminals from the two eyes initially overlap in the dorsal-lateral geniculate nucleus (dLGN) but subsequently refine to occupy nonoverlapping territories. Retinal activity is required to establish and maintain this segregation. We show that despite the presence of retinal activity, segregated projections desegregate when the structure of activity is altered. Early in development, spontaneous retinal activity in the no b-wave (nob) mouse is indistinguishable from that of wild-type mice, and eye-specific segregation proceeds normally. But, around eye-opening, spontaneous and visually evoked activity in nob retinas become abnormal, coincident with a failure to preserve precise eye-specific territories. Dark-rearing studies suggest that altered visual experience is not responsible. Transgenic rescue of the mutated protein (nyctalopin) within nob retinal interneurons, without rescuing expression in either retinal projection neurons or their postsynaptic targets in the dLGN, restores spontaneous retinal activity patterns and prevents desegregation. Thus, normally structured spontaneous retinal activity stabilizes newly refined retinogeniculate circuitry.

Animals↗

PubMed2003

Thalamocortical cells in the cat pulvinar nucleus transiently express nitric oxide synthase during development.

We examined the postnatal expression of the neuronal form of nitric oxide synthase (nNOS) within the pulvinar and lateral posterior (LP) nuclei of the cat thalamus using immunocytochemical techniques. During the first postnatal month, nNOS was expressed in many cells within the pulvinar nucleus and medial subdivision of the LP nucleus; fewer neurons in the lateral LP nucleus were stained by the nNOS antibody. We examined the pulvinar nucleus to determine what cell types express nNOS. A comparison of the soma sizes of nNOS-stained cells to the overall population of Nissl-stained cells and interneurons (stained with an antibody against glutamic acid decarboxylase) suggests that within the pulvinar nucleus, thalamocortical cells express nNOS during development. In addition, the nNOS antibody stained axon bundles that traverse the pulvinar nucleus to enter the optic radiations, suggesting that thalamocortical cell axons also contain nNOS during development. However, this staining pattern was dramatically reduced by postnatal day 42 and later ages; the size of the remaining nNOS-stained cells was closer to that of interneurons, a subset of which contain nNOS in the adult pulvinar nucleus. This contrasts with our previous findings that nNOS is specifically expressed within interneurons in the developing dorsal lateral geniculate nucleus (LGN) and serves as further confirmation that the pulvinar nucleus and LGN represent distinct categories of thalamic nuclei.

Animals↗

PubMed2003

Two distinct types of corticothalamic EPSPs and their contribution to short-term synaptic plasticity.

The lateral posterior nucleus (LPN) is innervated by two different morphological types of cortical terminals that originate from cortical layers V and VI. Here we describe two distinct types of excitatory postsynaptic potentials (EPSPs) that were recorded in the LPN after stimulation of corticothalamic fibers. These types of EPSPs differed in amplitude, latency, rise time, and response to increasing levels of stimulus intensity. The most frequently encountered EPSP, type I, displayed a longer latency and slower rise time than the less frequently encountered type II EPSP. Type I EPSPs also showed a graded increase in amplitude with increasing levels of stimulation, whereas type II EPSPs showed an all-or-none response. In response to repetitive stimulation (0.5-20 Hz), type I EPSPs displayed frequency-dependent facilitation, whereas type II EPSPs displayed frequency-dependent depression. Further details of these distinct forms of short-term synaptic plasticity were explored using paired-pulse stimuli. Pharmacology experiments revealed that both N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors are involved in corticothalamic synaptic transmission in the LPN and contribute to both synaptic facilitation and depression. Taken together with the results of our previous anatomical studies, these results suggest that type I EPSPs arise from stimulation of layer VI afferents, whereas type II EPSPs arise from stimulation of layer V inputs. Moreover, type I and II EPSPs in the LPN may be functionally similar to corticogeniculate and retinogeniculate EPSPs, respectively.

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↗

PubMed2003

Distinct firing properties of higher order thalamic relay neurons.

It has been proposed that the thalamus is composed of at least two types of nuclei. First-order relay nuclei transmit signals from the periphery to the cortex while higher order nuclei may route information from one cortical area to another. Although much is known about the functional properties of relay neurons in first-order nuclei, little is known about relay neurons belonging to higher-order nuclei. We investigated the electrophysiological properties of relay cells in a higher-order thalamic nucleus using in vitro intracellular recordings from thalamic slices of the rat's lateral posterior nucleus (LPN). We found neurons of the LPN possess many of the same membrane properties as first-order relay neurons. These included low-threshold calcium spikes (IT) and burst firing, a mixed cation conductance (IH) that prevented membrane hyperpolarization, and a transient K+ conductance that delayed spike firing (IA). The repetitive firing characteristics of LPN neurons were more distinct. One group of cells, located in the more caudal regions of the LPN responded to depolarizing current pulses with a train of action potentials or in a regular spiking (RS) mode. This form of firing showed a steep but highly linear increase in firing frequency with increasing levels of membrane depolarization. Another group of cells, located in the more rostral regions of the LPN, responded to depolarizing current pulses with clusters of high-frequency bursts or in a clustered spiking (CS) mode. The overall firing frequency rose nonlinearly with membrane depolarization, but the frequency of a given burst remained relatively constant. The caudal LPN receives input from the superior colliculus, whereas the rostral LPN receives input from layers V and VI of the visual cortex. Thus the RS and CS cells may be driven by subcortical and cortical inputs respectively, and the distinct temporal properties of their response modes may be a necessary component of the LPN circuitry.

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↗

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↗