Membrane and synaptic properties of developing lateral geniculate nucleus neurons during retinogeniculate axon segregation.

During the first postnatal month in the ferret (Mustela putorius furo), the projections from the retina to the lateral geniculate nucleus (LGN) become segregated into eye-specific layers and ON and OFF sublayers, a process that is thought to depend in part on neuronal activity. Remarkably, virtually nothing is known about the physiological features of LGN neurons during this period. We have recorded intracellularly from 46 A-layer neurons in slices of the ferret LGN between the ages of postnatal days 7 and 33. The passive membrane properties and current-voltage relationships of the developing neurons were similar in many, though not all, respects to those of adult LGN neurons. Action potentials in younger animals were smaller in amplitude and longer in duration than in older animals, but cells at all ages were capable of producing spike trains whose latency and spike number varied with stimulus intensity. In addition, cells at all ages responded with low-threshold potentials upon release from hyperpolarization. Slightly more than half of the LGN neurons responded to optic tract stimulation with excitatory postsynaptic potentials (EPSPs), inhibitory postsynaptic potentials (IPSPs), or EPSP-IPSP pairs, beginning with the youngest ages. Thus, as early as the second postnatal week, and much before the onset of pattern vision, LGN neurons have many of the membrane and synaptic properties of adult thalamic neurons. These data are consistent with LGN cells playing a significant role in activity-dependent reshaping of the retinogeniculate pathway.     

Effects of monocular deprivation on the lateral geniculate nucleus in a primate.

In many mammalian species, rearing with one eyelid closed produces a loss of vision in the deprived eye and a change in cell size in the lateral geniculate nucleus (LGN). In cats, the reduction in the size of deprived LGN cells has been correlated with a loss of one functional class of cells, Y cells. In primates, such as galago, LGN cells also exhibit marked changes in size with deprivation. In the present study we recorded from single cells in the LGN of monocularly deprived galagos to determine if such changes in cell size would be accompanied by changes in physiological properties. The results revealed no alterations in the distribution or functional properties of any cell class. The differences in the effects of monocular deprivation on the function of LGN cells in cats and primates are most easily explained by a fundamental difference in visual system anatomy. In cats, different classes of retinal afferents (X vs. Y) are in a position to compete for postsynaptic LGN neurons: in primates, segregation of cell classes into different layers may preclude such developmental interactions.     

Early discordant binocular vision disrupts signal transfer in the lateral geniculate nucleus.

The mammalian lateral geniculate nucleus (LGN) is known to regulate signal transfer from the retina to the brain neocortex in a highly complex manner. Besides inputs from the brainstem, extraretinal inputs via corticogeniculate projections and local inhibitory neurons modulate signal transfer in the LGN. However, very little is known about whether the postnatal development of LGN signal-transfer mechanisms is influenced by early discordant binocular vision. By intraunit comparisons of responses between individual X-LGN cells and their direct retinal inputs, the efficiency of signal transfer was found permanently reduced due to an early interocular misalignment (strabismus). The contrast sensitivity and spatial resolution of cat LGN cells were significantly lower relative to their retinal inputs, and there was substantial decrease in signal-transfer speed. The observed physiological deficits were associated with immature X-retinogeniculate axon arbors. Thus, contrary to previous ideas, conflicting binocular inputs can produce neural deficits in subcortical visual structures.     

The distribution of response spectra in the lateral geniculate nucleus compared with reflectance spectra of Munsell color chips

This paper compares the spectral response curves of cells in the lateral geniculate nucleus (LGN) with the reflectance spectra of a large sample of Munsell color chips. By examining the color chips with methods used by neural response researchers and the LGN cells with methods used by psychophysical color researchers, we obtain insights that may be useful for advancing knowledge in both fields. For LGN cells, the prevailing view is that they tend to be clustered into distinct types or along discernible lines or planes when data obtained from selected light stimuli are represented in a three-dimensional space derived from cone contributions. In contrast, the Munsell color chips are viewed as rather evenly distributed in a three-dimensional perceptual space based on the psychophysical judgment of surface colors. We demonstrate that, when the Munsell chips are viewed in the space typically applied to LGN cells, the distribution appears similar to that of the cells and vice versa. We show why this result occurs and suggest that it has implications for studies in both fields.     

Dendritic current flow in relay cells and interneurons of the cat''s lateral geniculate nucleus.

We used a passive, steady-state cable model to simulate current flow within the dendritic arbors of relay cells and interneurons in the cat's lateral geniculate nucleus. In confirmation of our previous work on relay cells, we found them to be electronically compact; thus a postsynaptic potential generated anywhere in a relay cell's dendritic arbor spreads with relatively little attenuation throughout the arbor and to its soma. An interneuron is very different. Its arbor is much more extensive electronically with the result that a postsynaptic potential significantly affects only local areas of the dendritic arbor, and only inputs to proximal dendrites or to the soma will much affect the soma. Since much of the interneuron's synaptic output derives from dendritic terminals that are both presynaptic and postsynaptic, its dendritic arbor may contain many local circuits that perform neuronal computations independently of each other, and this processing might be invisible to the soma. Furthermore, these interneurons possess conventional axonal outputs, and these contact postsynaptic profiles that are quite different from the postsynaptic targets of the dendritic terminals. Presumably, the axonal output reflects the integrated computations performed on proximal synaptic inputs, and it uses conventional action potentials to convey this output. We suggest that the interneuron does double duty: its dendritic arbor is used for many independent local circuits that perform one set of neuronal computations, and its axonal output represents conventional neuronal integration of proximal synaptic inputs.     

Modeling lateral geniculate nucleus cell response spectra and Munsell reflectance spectra with cone sensitivity curves

We find that the cell response spectra of lateral geniculate nucleus cells, as well as the reflectance spectra of Munsell color chips, may be modeled by using the cone sensitivity functions of the long and medium cones. We propose a simple model for how the neural signals from the photoreceptors might be combined in the retina to closely approximate the reflectance spectra of Munsell color chips without input from the short cone.     

Glial cells develop a laminar pattern before neuronal cells in the lateral geniculate nucleus.

The lateral geniculate nucleus, which lies between the retina and the striate cortex in the visual pathway of mammals, is often made up of several distinctive cell layers, or laminae. We have used immunohistochemical methods to localize two glial cell intermediate filament proteins, glial fibrillary acidic protein and vimentin, and have found that layering of glial cells is evident before neuronal cell layers develop in the lateral geniculate nucleus. The correlation between glial cell lamination and neuronal lamination is consistent with the suggestion that glia are guiding neurons not only during the early postmitotic migratory phase of development but also during the later formation of functional divisions such as layers and nuclei.     

Retinotopic mapping of lateral geniculate nucleus in humans using functional magnetic resonance imaging

Subcortical nuclei in the thalamus, which play an important role in many functions of the human brain, provide challenging targets for functional mapping with neuroimaging techniques because of their small sizes and deep locations. In this study, we explore the capability of high-resolution functional magnetic resonance imaging at 4 Tesla for mapping the retinotopic organization in the lateral geniculate nucleus (LGN). Our results show that the hemifield visual stimulation only activates LGN in the contralateral hemisphere, and the lower-field and upper-field visual stimulations activate the superior and inferior portion of LGN, respectively. These results reveal a similar retinotopic organization between the human and nonhuman primate LGN and between LGN and the primary visual cortex. We conclude that high-resolution functional magnetic resonance imaging is capable of functional mapping of suborganizations in small nuclei together with cortical activation. This will have an impact for studying the thalamocortical networks in the human brain.     

Some transformations of color information from lateral geniculate nucleus to striate cortex

We have recorded the responses of single cells in the lateral geniculate nucleus (LGN) and striate cortex of the macaque monkey. The response characteristics of neurons at these successive visual processing levels were examined with isoluminant gratings, cone-isolating gratings, and luminance-varying gratings. The main findings were: (i) Whereas almost all parvo- and konio-cellular LGN cells are of just two opponent-cell types, either differencing the L and M cones (L(o) and M(o) cells), or the S vs. L + M cones (S(o) cells), relatively few striate cortex simple cells show chromatic responses along these two cardinal LGN axes. Rather, most are shifted away from these LGN chromatic axes as a result of combining the outputs (or the transformed outputs) of S(o) with those of L(o) and/or M(o) cells. (ii) LGN cells on average process color information linearly, exhibiting sinusoidal changes in firing rate to isoluminant stimuli that vary sinusoidally in cone contrast as a function of color angle. Some striate cortex simple cells also give linear responses, but most show an expansive response nonlinearity, resulting in narrower chromatic tuning on average at this level. (iii) There are many more +S(o) than -S(o) LGN cells, but at the striate cortex level -S(o) input to simple cells is as common as +S(o) input. (iv) Overall, the contribution of the S-opponent path is doubled at the level of the striate cortex, relative to that at the LGN.     

N-methyl-D-aspartate receptors contribute to excitatory postsynaptic potentials of cat lateral geniculate neurons recorded in thalamic slices.

Neurons of the cat's dorsal lateral geniculate nucleus were recorded intracellularly to study the contribution of N-methyl-D-aspartate (NMDA) receptors to excitatory postsynaptic potentials (EPSPs) and low-threshold calcium spikes. EPSPs were evoked by stimulation of retinogeniculate axons in the optic tract and/or corticogeniculate axons in the optic radiations; EPSPs from both sources were similar. These EPSPs had one or two components, and the second component had several characteristics of NMDA receptor-mediated events. For example, EPSP amplitude decreased when neurons were hyperpolarized and increased when stimulus frequency was increased; these EPSPs could also be blocked reversibly by application of the selective NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV). We also studied the influence of NMDA receptors on low-threshold calcium spikes, which are large, voltage- and calcium-dependent depolarizations that are often accompanied by high-frequency action potential discharge. APV blocked synaptically activated low-threshold calcium spikes, but APV had no effect on low-threshold calcium spikes that were elicited by current injection. Therefore, APV does not appear to have a direct effect on the T-type calcium channel that is involved in generation of low-threshold calcium spikes. The voltage and frequency dependence of the NMDA receptor-mediated component of the EPSPs, as well as its ability to trigger low-threshold calcium spikes, provide for complex signal processing in the lateral geniculate nucleus.     

Brainstem norepinephrine neurons mediate ethanol-evoked pressor response but not baroreflex dysfunction

BACKGROUND: Ethanol elicits strain-dependent blood pressure and baroreflex sensitivity responses in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats; the mechanisms underlying these divergent effects are not clear. The authors tested the hypothesis that differential neuronal actions of ethanol may account for these strain-dependent responses. To this end, the authors investigated the direct effects of ethanol on norepinephrine (NE)-containing neurons in the rostral ventrolateral medulla (RVLM), which modulate sympathetic neuronal activity, and on c-Jun-expressing neurons in the nucleus tractus solitarius (NTS), whose activity is inversely correlated with baroreflex sensitivity. METHODS: In a newly developed model system in conscious, freely moving rats, the effect of intra-RVLM or intra-NTS ethanol was investigated on neuronal NE at the microinjection site (in vivo electrochemistry), blood pressure, heart rate, spontaneous baroreflex sensitivity, and c-Jun expression in the NTS. RESULTS: Ethanol (1, 5, or 10 microg) microinjection into the RVLM elicited dose-dependent increases in RVLM NE and blood pressure in SHRs but not in WKY rats. Ethanol had no effect on the activity of the NE-containing neurons in the NTS of either strain. However, baroreflex dysfunction elicited by intra-NTS ethanol in conscious WKY rats was associated with enhanced expression of c-Jun in the NTS. CONCLUSIONS: (1) Ethanol activation of the NE-containing neurons in the RVLM of SHRs contributes to the centrally mediated pressor response, (2) the NE-containing neurons in the NTS are not involved in ethanol-induced baroreflex dysfunction, and (3) direct activation of the c-Jun-containing neurons in the NTS is implicated in baroreflex dysfunction elicited by ethanol in normotensive rats.     

Substance P targets sympathetic control neurons in the paraventricular nucleus

The paraventricular nucleus (PVN) contains spinally-projecting neurons implicated in fine-tuning the cardiovascular system. In vivo activity of "presympathetic" parvocellular neurons is suppressed by tonic inhibition from GABA-ergic inputs, inhibition of which increases sympathetic pressor activity and heart rate. Targeting of this specific neuronal population could potentially limit elevations of heart rate and blood pressure associated with disease. Here we show, for the first time, that "presympathetic" PVN neurons are disinhibited by the neuropeptide substance P (SP) acting via tachykinin NK1 receptor inhibition of GABA(A) currents. Application of SP to the paraventricular nucleus of rats increases heart rate and blood pressure. In in vitro brain slice experiments, in the presence of GABA, 1 micromol/L SP increased action current frequency by a factor of 2.7+/-0.6 (n=5, P< or =0.05, ANOVA). Furthermore, 1 micromol/L SP inhibited GABA(A) currents by 70+/-8% (n=8, P< or =0.005 paired t test). These effects were abolished by NK1 antagonists, but not NK2 and NK3 antagonists. GABA(A) inhibition was not reproduced by NK2 or NK3 agonists. The inhibition of parvocellular GABA(A) currents by SP was also abolished by a protein kinase C (PKC) inhibitor peptide and mimicked by application of phorbol-12-myristate-13-acetate (PMA), implicating a PKC-dependent mechanism. Single-channel analysis indicates that SP acts through reduction of channel mean open-time (cmot): GABA(A) cmot being reduced by approximately 60% by SP (P< or =0.05 ANOVA, Bonferroni). These data suggest that tachykinins mediate their pressor activity by increasing the excitability of spinally-projecting neurons and identifies NK1 receptors as potential targets for therapeutic modulation of the cardiovascular system.     

The function of bursts of spikes during visual fixation in the awake primate lateral geniculate nucleus and primary visual cortex

When images are stabilized on the retina, visual perception fades. During voluntary visual fixation, however, constantly occurring small eye movements, including microsaccades, prevent this fading. We previously showed that microsaccades generated bursty firing in the primary visual cortex (area V-1) in the presence of stationary stimuli. Here we examine the neural activity generated by microsaccades in the lateral geniculate nucleus (LGN), and in the area V-1 of the awake monkey, for various functionally relevant stimulus parameters. During visual fixation, microsaccades drove LGN neurons by moving their receptive fields across a stationary stimulus, offering a likely explanation of how microsaccades block fading during normal fixation. Bursts of spikes in the LGN and area V-1 were associated more closely than lone spikes with preceding microsaccades, suggesting that bursts are more reliable than are lone spikes as neural signals for visibility. In area V-1, microsaccade-generated activity, and the number of spikes per burst, was maximal when the bar stimulus centered over a receptive field matched the cell's optimal orientation. This suggested burst size as a neural code for stimuli optimality (and not solely stimuli visibility). As expected, burst size did not vary with stimulus orientation in the LGN. To address the effectiveness of microsaccades in generating neural activity, we compared activity correlated with microsaccades to activity correlated with flashing bars. Onset responses to flashes were about 7 times larger than the responses to the same stimulus moved across the cells' receptive fields by microsaccades, perhaps because of the relative abruptness of flashes.     

Retinal afferent arborization patterns, dendritic field orientations, and the segregation of function in the lateral geniculate nucleus of the monkey

Optic tract fibers and cell bodies in the lateral geniculate nucleus of the monkey were studied intracellularly with micropipette electrodes containing the marker enzyme horseradish peroxidase. Single optic-tract fibers always projected to only one of the six geniculate layers. The majority of the axons innervating the four parvocellular laminae were red/green opponent color units; their terminations formed cylindrical columns that were perpendicular to the layers. In similar fashion, the geniculate cells in the parvocellular layers were mostly red/green units with narrow, bipolar dendritic fields oriented normal to the laminar borders. The majority of the retinal axons ending in parvocellular layers 6 and 5 were on-center units; nearly all geniculate cells in these two laminae were also on-center neurons. In layers 4 and 3 most terminating optic-tract fibers, as well as the geniculate cells themselves, were off-center units. All axons projecting to the magnocellular layers were broad-band units with spherical terminal arborizations. The magnocellular geniculate neurons, which were also broad band, had extensive spherical dendritic fields that often crossed laminar borders. Thus, the terminal patterns of each class of retinogeniculate axon closely resembled the dendritic orientations of the functionally related geniculate target cells.     

Statistics of lateral geniculate nucleus (LGN) activity determine the segregation of ON/OFF subfields for simple cells in visual cortex

The receptive fields for simple cells in visual cortex show a strong preference for edges of a particular orientation and display adjacent excitatory and inhibitory subfields. These subfields are projections from ON-center and OFF-center lateral geniculate nucleus cells, respectively. Here we present a single-cell model using ON and OFF channels, a natural scene environment, and synaptic modification according to the Bienenstock, Cooper, and Munro (BCM) theory. Our results indicate that lateral geniculate nucleus cells must act predominantly in the linear region around the level of spontaneous activity, to lead to the observed segregation of ON/OFF subfields.     

Substance P-containing neurons of the avian suprachiasmatic nucleus project directly to the nucleus of Edinger-Westphal.

Retrograde and anterograde pathway tracing techniques were used in the pigeon to study afferent visual input from the suprachiasmatic nucleus (SCN) of the hypothalamus to the nucleus of Edinger-Westphal (EW), the parasympathetic visceral efferent component of the oculomotor complex. Horseradish peroxidase injected into the EW retrogradely labeled numerous neurons in the contralateral SCN, a retinorecipient hypothalamic nucleus, as well as a few neurons in the ipsilateral SCN. Autoradiographic orthograde pathway tracing experiments confirmed that the SCN projects heavily upon the medial subdivision of the contralateral EW and lightly upon the medial subdivision of the ipsilateral EW. Some neurons of the SCN contain substance P and a substance P-positive plexus of fibers was seen in precisely that medial portion of the EW to which the SCN was found to project in the autoradiographic experiments. This substance P-positive fiber plexus in the medial EW was eliminated by bilateral electrolytic lesions of the SCN. These results show that the avian suprachiasmatic nucleus has a heavy contralateral and a much lighter ipsilateral projection to the medial subdivision of the EW and that this projection may be largely substance P positive. Previous studies have suggested that neurons of the medial EW specifically project to the neurons of the ciliary ganglion that control the choriocapillary blood flow of the eye. Since the SCN has been implicated in the control of circadian rhythms in vertebrates, the projection of the SCN to the EW may represent a pathway by which a circadian rhythmicity is imposed on choriocapillary blood flow. Alternatively or in addition, the SCN-EW pathway described in this paper may provide the central neural substrate for a homeostatic regulatory mechanism by which choriocapillary blood flow is controlled by the intensity of retinal illumination.