PubMed HealthSearch

Biomedical subjects

S M Sherman

Publications and source records attributed to S M Sherman.

At least 19 recordsLinked to original sources

Morphology of physiologically identified retinal X and Y axons in the cat's thalamus and midbrain as revealed by intraaxonal injection of biocytin.

Prior morphological studies of individual retinal X and Y axon arbors based on intraaxonal labeling with horseradish peroxidase have been limited by restricted diffusion or transport of the label. We used biocytin instead as the intraaxonal label, and this completely delineated each of our six X and 14 Y axons, including both thalamic and midbrain arbors. Arbors in the lateral geniculate nucleus appeared generally as has been well documented previously. Interestingly, all of the labeled axons projected a branch beyond thalamus to the midbrain. Each X axon formed a terminal arbor in the pretectum, but none continued to the superior colliculus. In contrast, 11 of 14 Y axons innervated both the pretectum and the superior colliculus, one innervated only the pretectum, and two innervated only the superior colliculus. Two of the Y axons were quite unusual in that their receptive fields were located well into the hemifield ipsilateral with respect to the hemisphere into which they were injected. These axons exhibited remarkable arbors in the lateral geniculate nucleus, diffusely innervating the C-laminae and medial interlaminar nucleus, but, unlike all other X and Y arbors, they did not innervate the A-laminae at all. In addition to these qualitative observations, we analyzed a number of quantitative features of these axons in terms of numbers and distributions of terminal boutons. We found that Y arbors contained more boutons than did X arbors in both thalamus and midbrain. Also, for axons with receptive fields in the contralateral hemifield (all X and all but two Y axons), 90-95% of their boutons terminated in the lateral geniculate nucleus; the other two Y axons had more of their arbors located in midbrain.

Animals

Latency variability of responses to visual stimuli in cells of the cat's lateral geniculate nucleus.

We constructed average histograms from responses evoked by flashing stimuli and noted previously described variations in the shape of the response profile, particularly with respect to sharpness of the peak. To express this variable, we measured the half-rise latency, which is the latency from stimulus onset required to reach half the maximum response. A short half-rise latency, which is characteristic of nonlagged cells, is associated with a brisk response and sharp peak; a long half-rise latency, characteristic of lagged cells, is associated with a sluggish response and broad peak. Nonlagged cells were readily seen; we attempted to identify cells with long latencies as lagged, but we were unable to do so unambiguously due to failure to observe lagged properties other than latency. We thus refer to these latter cells as having "lagged-like" responses to indicate that we are not certain whether these are indeed lagged cells. In addition to the histograms, we analyzed the individual response trials that were summed to create each histogram, and we used spike density analysis to estimate the initial response latency to the flashing spot for each trial. We found that lagged-like responses were associated with more variability in initial response latency than were nonlagged responses. We then employed an alignment procedure to eliminate latency variation from individual trials; that is, responses during individual trials were shifted in time as needed so that each had a latency equal to the average latency of all trials. We used these "aligned" trials to create a second, "aligned" response histogram for each cell. The alignment procedure had little effect on nonlagged responses, because these were already well aligned due to consistent response latencies amongst trials. For lagged-like responses, however, the alignment made a dramatic difference. The aligned histograms looked very much like those for nonlagged responses: the responses appeared brisk, with a sharply rising peak that was fairly high in amplitude. We thus conclude that the slow build up to a relatively low peak of firing of the lagged-like response histogram is not an accurate reflection of responses on single trials. Instead, the sluggishness of lagged-like responses inferred from average response histograms results from temporal smearing due to latency variability amongst trials. We thus conclude that there is relatively little difference in briskness between nonlagged and lagged-like responses to single stimuli.

Animals

Effects of brain stem parabrachial activation on receptive field properties of cells in the cat's lateral geniculate nucleus.

1. The lateral geniculate nucleus is the primary thalamic relay for the transfer of retinal signals to the visual cortex. Geniculate cells are heavily innervated from nonretinal sources, and these modify retinogeniculate transmission. A major ascending projection to the lateral geniculate nucleus arises from cholinergic cells in the parabrachial region of the brain stem. This is an important pathway in the ascending control of arousal. In an in vivo preparation, we used extracellular recordings to study the effects of electrical activation of the parabrachial region on the spontaneous activity and visual responses of X and Y cells in the lateral geniculate nucleus of the cat. 2. We studied the effects of two patterns of parabrachial activation on the spontaneous activity of geniculate cells. Burst stimulation consisted of a short pulse at high frequency (16 ms at 250 Hz). Train stimulation was of longer duration at lower frequency (e.g., 1 s at 50 Hz). The firing rate of almost all geniculate cells was enhanced by either pattern of stimulation. However, the burst pattern of stimulation elicited a short, modulated response with excitatory and inhibitory epochs. We found that the different epochs could differentially modulate the visual responses to drifting gratings. Thus the temporal alignment of the brain stem and visual stimuli was critical with burst stimulation, and varied alignments could dramatically confound the results. In comparison, the train pattern of stimulation consistently produced a relatively flat plateau of increased firing, after a short initial period of more variable effects. We used the less confounding pattern of train stimuli to study the effects of parabrachial activation on visual responses. 3. Our main emphasis was to examine the parabrachial effects on the visual responses of geniculate cells. For most visual stimuli, we used drifting sine wave gratings that varied in spatial frequency; these evoked modulated responses from the geniculate cells. Parabrachial activation enhanced the visual responses of almost all geniculate cells, and this enhancement included both increased depth of modulation and greater response rates. 4. Our results were incorporated quantitatively into a difference-of-Gaussians model of visual receptive fields in order to study the parabrachial effects on the spatial structure of the receptive field. This model fit our data well and provided measures of the response amplitude and radius of the receptive field center (Kc and Rc, respectively) and the response amplitude and radius of the receptive field surround (Ks and Rs, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Rearing with monocular lid suture induces abnormal NADPH-diaphorase staining in the lateral geniculate nucleus of cats.

We investigated the changes in NADPH-diaphorase staining that occur in the lateral geniculate nucleus of cats following rearing with monocular lid suture. This staining allows visualization of the synthesizing enzyme of nitric oxide, a neuromodulator associated with plasticity. In the lateral geniculate nucleus of normally reared cats, NADPH-diaphorase exclusively labels the axons and terminals of an input from the parabrachial region of the brainstem; no geniculate cells in the A-laminae are labeled. Early monocular lid suture has no obvious effect on the NADPH-diaphorase staining of parabrachial axons. However, this lid suture results in the abnormal appearance of NADPH-diaphorase staining for geniculate somata. These cells are located primarily in the nondeprived laminae. Double-labeling experiments indicate that these cells with abnormal NADPH-diaphorase reactivity are Y relay cells: NADPH-diaphorase staining is found in cells retrogradely labeled from visual cortex; it is found in cells labeled with a monoclonal antibody for CAT-301, which selectively targets Y cells; it is not found in cells labeled with an anti-GABA antibody, which targets interneurons. Also, NADPH-diaphorase labeled cells are among the largest cells in the nondeprived laminae, again suggesting that they are Y relay cells. We cannot suggest a specific mechanism for this induction of NADPH-diaphorase labeling, but it does not seem to be due to abnormal binocular competition induced by the monocular lid suture.

Adaptation, Physiological

GABAergic projection from the basal forebrain to the visual sector of the thalamic reticular nucleus in the cat.

We examined the projection from the basal forebrain to thalamic and cortical regions of the visual system in cats, with particular reference to the visual sector of the thalamic reticular nucleus, the lateral geniculate nucleus, and the striate cortex. First, we made injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the visual sector of the thalamic reticular nucleus and found cells labeled by retrograde transport in the lateral nucleus basalis magnocellularis. Injection of biocytin into the basal forebrain resulted in the anterograde labeling of a dense band of fibers and terminals within the entire thalamic reticular nucleus; this labeling extended through the visual sector including the perigeniculate nucleus. No orthograde labeling was found in the lateral geniculate nucleus. Next, we addressed the issue of putative neurotransmitters used by this pathway using a variety of immunocytochemical and histochemical markers. In this fashion, we identified two populations of cells in the nucleus basalis magnocellularis of the cat; large cholinergic cells that contain choline acetyltransferase, NADPH-diaphorase, and calbindin and that project to striate cortex and smaller cells that contain gamma-aminobutyric acid (GABA), glutamic acid decarboxylase, and parvalbumin and that project to the visual sector of the thalamic reticular nucleus. We also examined at the electron microscopic level terminals in the visual sector of the thalamic reticular nucleus that were labeled from a biocytin injection in the basal forebrain. Most of these terminals form symmetric contacts onto dendrites and were revealed by postembedding immunocytochemical staining to be positive for GABA.

Acetylcholine

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.

Animals

Ultrastructure of synapses from the pretectum in the A-laminae of the cat's lateral geniculate nucleus.

We have recently shown in cats that many neurons projecting to the lateral geniculate nucleus from the pretectum use gamma-amino butyric acid (GABA) as their neurotransmitter. We sought to determine the morphology of synaptic terminals and synapses formed by these pretectal axons and the extent to which they resemble other GABAergic terminals found in the geniculate neuropil (i.e., from geniculate interneurons and cells of the nearby perigeniculate nucleus). To do this, we labeled a population of pretectal axons with the anterograde tracer Phaseolus vulgaris leucoagglutinin and analyzed the morphology and synaptology of labeled pretectal terminals in the A-laminae of the cat's lateral geniculate nucleus. The pretectal projection, which arises primarily from the nucleus of the optic tract (NOT), provides synaptic innervation to elements in the geniculate neuropil. The labeled NOT terminals are densely packed with vesicles, contain dark mitochondria, and form symmetrical synaptic contacts. These are characteristics of the F1 type of terminal, and we know from other studies that GABAergic axon terminals from interneurons and perigeniculate cells also give rise to F1 terminals. We compared our population of NOT terminals with labeled perigeniculate and unlabeled F1 terminals selected from the geniculate neuropil and found that all three populations share many morphological characteristics. Both qualitative and quantitative assessments of the pretectal terminals suggest that these are a type of F1 terminal. Most pretectal terminals selectively form synapses onto geniculate profiles that contain irregularly distributed vesicles and dark mitochondria and that are postsynaptic to other types of terminals. These postsynaptic targets thus exhibit features of another class of inhibitory, GABAergic terminal known as F2 terminals, which are the specialized appendages of geniculate interneurons. Pretectal inputs, being GABAergic, may thus serve to inhibit local interneuronal outputs. Pretectal axons also innervate the perigeniculate nucleus, in which the only targets are the other main type of inhibitory, GABAergic neurons. These results suggest that the pretectum may facilitate retinal transmission through the lateral geniculate nucleus by providing inhibition to the local inhibitory cells: the interneurons and probably perigeniculate cells. This would serve to release geniculate relay cells from inhibition.

Animals

Evidence that cholinergic axons from the parabrachial region of the brainstem are the exclusive source of nitric oxide in the lateral geniculate nucleus of the cat.

We investigated the source of axons and terminals in the cat's lateral geniculate nucleus that stain positively for NADPH-diaphorase. The functional significance of such staining is that NADPH-diaphorase is identical to the enzyme nitric oxide synthetase, and thus it is thought to reveal cells and axons that use nitric oxide as a neuromodulator. Within the lateral geniculate and adjacent perigeniculate nuclei, a dense network of axons and terminals is labeled for NADPH-diaphorase. The pattern of NADPH-diaphorase staining here is remarkably similar to that of choline acetyltransferase (ChAT) staining, suggesting that the source of these axons and terminals might be the parabrachial region of the brainstem because this provides the major cholinergic input to the lateral geniculate nucleus. In other areas of the brain to which parabrachial axons project, there is also a similar staining pattern for NADPH-diaphorase and ChAT. Furthermore, the patterns of cell staining within the parabrachial region for NADPH-diaphorase and ChAT are virtually identical. However, the relationship between ChAT and NADPH-diaphorase staining for the parabrachial region is not a general property of cholinergic neurons. Other cholinergic cells and axons, such as the trochlear nerve, the oculomotor nerve and nucleus, and the parabigeminal nucleus, which all label densely for ChAT, stain poorly or not at all for NADPH-diaphorase. It is significant that the parabigeminal nucleus, which provides a cholinergic input to the lateral geniculate nucleus, has no cells that label for NADPH-diaphorase. We used double labeling methods to identify further the source of NADPH-diaphorase staining in the lateral geniculate nucleus. We found that parabrachial cells co-localize NADPH-diaphorase and ChAT. Noradrenergic and serotoninergic cells in the brainstem also innervate the lateral geniculate nucleus, but we found that none of these co-localize NADPH-diaphorase. Finally, by combining NADPH-diaphorase histochemistry with retrograde labeling of cells that project to the lateral geniculate nucleus, we found that the cholinergic cells of the parabrachial region are essentially the sole source of NADPH-diaphorase in the lateral geniculate nucleus. We thus conclude that cells from the parabrachial region that innervate the lateral geniculate nucleus use both acetylcholine and nitric oxide for neurotransmission, and that this is virtually the only afferent input to this region that uses nitric oxide.

Animals

Effects of membrane voltage on receptive field properties of lateral geniculate neurons in the cat: contributions of the low-threshold Ca2+ conductance.

1. Thalamic relay cells, including those of the lateral geniculate nucleus, display a low-threshold spike (LT spike), which is a large depolarization due to an increased Ca2+ conductance. Typically riding the crest of each LT spike is a burst of from two to seven action potentials, which we refer to as the LT burst. The LT spike is voltage dependent, because if the cell's resting membrane potential is more depolarized than roughly -60 mV, the LT spike is inactivated, but if more hyperpolarized, the spike is deinactivated and can be activated by a depolarization, such as from an afferent excitatory postsynaptic potential (EPSP). Thalamic relay cells thus display two response modes: a relay or tonic mode, when the cell is depolarized and LT spikes are inactivated, leading to tonic firing of action potentials; and a burst mode, when the cell is hyperpolarized and tends to respond with LT spikes and their associated bursts of action potentials. 2. We were interested in the contribution of the LT spike on the transmission of visually evoked signals through geniculate relay cells to visual cortex. We recorded intracellularly from geniculate cells in an anesthetized, paralyzed, in vivo cat preparation to study the effects of membrane voltage, and thus the presence or absence of LT spikes, on responses to drifting sine-wave gratings. We monitored the visually evoked responses of 14 geniculate neurons (6 X, 7 Y, and 1 unclassified) at different membrane potentials at which LT spikes were inactivated or deinactivated. 3. Changing membrane voltage during visual stimulation switched the response mode of every cell between the relay and burst modes. In the burst mode, LT spikes occurred in phase with the visual stimulus and not at rhythmic intervals uncorrelated to visual stimuli. To any given stimulus cycle, the cell responded usually with an LT burst or a tonic response, and rarely was more than one LT burst evoked by a stimulus cycle. Occasionally a single cycle evoked both an LT burst and tonic response, but always the LT burst occurred first. 4. The spatial tuning characteristics of the cells did not differ dramatically as a function of membrane potential, because the tuning of the LT bursts was quite similar to that of the tonic response component. Although we did not obtain complete temporal tuning properties, we did note that hyperpolarized cells responded reliably with LT bursts at several temporal frequencies. 5. A consistent difference was seen between the LT burst and tonic response components in terms of response linearity.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Relative contributions of burst and tonic responses to the receptive field properties of lateral geniculate neurons in the cat.

1. In an anesthetized, paralyzed in vivo preparation, we recorded extracellular responses of 61 geniculate neurons (2 W, 25 X, 33 Y, and 1 mixed) to drifting sine-wave gratings of various spatial frequency, temporal frequency, and contrast. Our goal was to study the differential contributions to these visual responses of bursting caused by voltage dependent, low-threshold (LT) Ca2+ spikes and of purely tonic responses unrelated to LT spikes. Cells responding with LT spikes are said to be in the burst firing mode and those responding in a purely tonic fashion to be in the relay or tonic firing mode. We separated the total visual response into LT burst and tonic components by use of the empirical criteria set forth in our intracellular study described in the previous paper (Lu et al. 1992). A response component was considered to be an LT burst if its action potentials displayed interspike intervals < or = 4 ms and if the first spike in the burst episode occurred after a silent period of > or = 100 ms (or > or = 50 ms when the neuron responds to visual stimuli at temporal rates > or = 8 Hz). All other activity is considered to be part of the tonic response. 2. In addition to LT bursts, we recognized another type of burst response, the high-threshold (HT) burst. These also have clusters of action potentials with interspike intervals < or = 4 ms. However, HT bursts, unlike LT bursts, lack a preburst silent period. HT bursts are part of the tonic response component and merely reflect the gradual decrease in interspike intervals that occurs as the cell becomes more depolarized and thus more responsive. Thus interspike interval is a necessary but insufficient criterion to identify LT bursts. 3. Visually evoked LT bursts were recorded among W, X, and Y cells. When evoked, LT bursts occurred in phase with drifting sine-wave grating stimuli at a rate never exceeding one per stimulus cycle. In response to individual cycles of the visual stimulus, LT bursts could comprise the total response, a tonic component could comprise the total response, or an LT burst and tonic component could be mixed. When a stimulus evoked a mixture of LT bursts and tonic response components, LT bursts were always the first response. 4. Of the 61 cells tested with grating stimuli, 47 exhibited LT bursts and 14 did not. Those that did exhibited varying amounts of burstiness.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Electron-microscopic analysis of synaptic input from the perigeniculate nucleus to the A-laminae of the lateral geniculate nucleus in cats.

The perigeniculate nucleus of carnivores is thought to be a part of the thalamic reticular nucleus related to visual centers of the thalamus. Physiological studies show that perigeniculate neurons, which are primarily GABAergic, provide feedback inhibition onto neurons in the lateral geniculate nucleus. However, little is known about the anatomical organization of this feedback pathway. To address this, we used two complementary tracing methods to label perigeniculate axons for electron microscopic study in the geniculate A-laminae: intracellular injection of horseradish peroxidase (HRP) to fill an individual perigeniculate cell and its axon; and anterograde transport of Phaseolus vulgaris leucoagglutinin to label a population of perigeniculate axons. Labeled perigeniculate terminals display features of F1 terminals in the geniculate neuropil: they are small, contain dark mitochondria, and form symmetric synaptic contacts. We found that most of the perigeniculate terminals (greater than 90%) contact geniculate cell dendrites in regions that also receive a rich innervation from terminals deriving from visual cortex (e.g., "cortico-recipient" dendrites). The remainder of the perigeniculate synapses (10%) contacted dendrites in regions that also received direct retinal input (e.g., "retino-recipient" dendrites). Serial reconstruction of segments of dendrites postsynaptic to perigeniculate terminals suggests that these terminals contact both classes of relay cell in the A-laminae (X and Y), although our preliminary conclusion is that an individual perigeniculate cell contacts only one class. Finally, our quantitative comparison between labeled perigeniculate terminals and unlabeled F1 terminals indicates that these perigeniculate terminals form a distinct subset of F1 terminals. We quantitatively compared the labeled perigeniculate terminals to unlabeled F1 terminals. Although the parameters of the perigeniculate terminals fell entirely within the range of those for the unlabeled F1 terminals, as populations, we found consistent differences between these two groups. We thus conclude that, as populations, other sources of F1 terminals are morphologically distinct from perigeniculate terminals and innervate different targets.

Animals

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)

Action Potentials

A GABAergic projection from the pretectum to the dorsal lateral geniculate nucleus in the cat.

To study the projection from the pretectum to the lateral geniculate nucleus, we placed wheat-germ agglutinin conjugated to horseradish peroxidase into the lateral geniculate nuclei of six cats, allowed this marker to be retrogradely transported by afferent axons to their parent somata in the pretectum, and revealed the label in these cells with stabilized tetramethylbenzidine histochemistry. In three cases we made large pressure injections that completely infiltrated the lateral geniculate nucleus and extended into neighboring thalamic nuclei; in the other three we made smaller iontophoretic injections largely confined to the A- and C-laminae of the lateral geniculate nucleus. In both types of injection we found labeled pretectal cells mainly in the nucleus of the optic tract but also found some cells labeled in the olivary pretectal nucleus and the posterior pretectal nucleus. After one of the larger injections we analysed both sides of the pretectum and found that 11% of the labeled cells were located contralaterally and were distributed in the same three nuclei. We analysed only the ipsilateral side in the remaining five cats. In those five experiments we also immunohistochemically stained the pretectal sections with an antibody directed against the neurotransmitter, GABA. Of the retrogradely labeled pretectal cells, 40% were also labeled for GABA, and those were similar in soma size (350 microns 2 in cross-sectional area) to those labeled only with the retrograde marker (331 microns 2). GABA-positive cells not labeled by retrograde transport were smaller (246 microns 2) than either of these other cells populations. These results indicate that at least 40% of the cells involved in the projection from the pretectum to the lateral geniculate nucleus are GABAergic. We suggest that this extrathalamic projection may serve to inhibit thalamic GABAergic cells. This, in turn, would disinhibit geniculate relay cells, thereby facilitating the geniculate relay of retinal information to cortex.

Afferent Pathways

Morphology and axonal projection patterns of individual neurons in the cat perigeniculate nucleus.

1. The lateral geniculate nucleus is the primary thalamic relay through which retinal signals pass en route to cortex. This relay is gated and can be suppressed by activity among local inhibitory neurons that use gamma-aminobutyric acid (GABA) as a neurotransmitter. In the cat, a major source of this GABAergic inhibition seems to arise from cells of the perigeniculate nucleus, which lies just dorsal to the A-laminae of the lateral geniculate nucleus. However, the morphological characteristics of perigeniculate cells, and particularly the projection patterns of their axons, have never been fully characterized. We thus examined the morphology of these cells: individually by intracellular injection of horseradish peroxidase (HRP) and en masse with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHAL). 2. We recorded from 12 perigeniculate cells that we impaled and successfully labeled with HRP. These cells exhibited response properties generally consistent with those described previously. They had long response latencies to stimulation of the optic chiasm and relatively large, often diffuse, receptive fields. The visually evoked responses of most of the cells were dominated by one eye. Compared with cells of the lateral geniculate nucleus, perigeniculate cells had large somata (517 +/- 136 microns 2 in cross-sectional area, mean +/- SD), which were fusiform or multipolar in shape, and dendritic arbors that extended a considerable distance (1,095 +/- 167 microns) parallel to the border between the perigeniculate and lateral geniculate nuclei. Terminal arbors of some dendrites were quite complex and beaded. 3. The axons of six perigeniculate cells were labeled sufficiently well to trace and reconstruct over a considerable distance. Each of these axons formed branches that descended to innervate the lateral geniculate nucleus, and this geniculate innervation was exclusively limited to the A-laminae. Terminal boutons within the A-laminae were nearly all en passant, which gave the axons a beaded appearance. Furthermore, branches of five of these six axons provided local innervation of the perigeniculate nucleus, generally within each labeled cell's own dendritic arbor. Three of the cells also exhibited an axon branch that extended medially and caudally away from the soma, but we were unable to trace these axon branches to their targets. 4. Within the lateral geniculate nucleus, each arbor of perigeniculate axons derived from two main components. One was a narrow, sparse medial component that innervated laminae A and A1.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

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.

Animals

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.

2-Amino-5-phosphonovalerate

Brainstem control of response modes in neurons of the cat's lateral geniculate nucleus.

The visual pathway from retina through the lateral geniculate nucleus to visual cortex in the cat is comprised of several parallel neuronal streams that independently analyze different aspects of the visual scene. The best known of these are the X and Y pathways that relay through the geniculate A laminae. Recent receptive-field studies of retinal and geniculate neurons suggest that there is a further elaboration of cell types at the level of the lateral geniculate nucleus. That is, two types of geniculate X cells with different temporal patterns of responses to visual stimuli are recognized, one with "nonlagged" features, exhibiting shorter response latencies and another with "lagged" features; all retinal X cells are nonlagged. We asked whether nonlagged and lagged responses represent different cell classes or two response modes of the same cells, perhaps under the control of nonretinal afferents to these relay cells. Accordingly, we studied the effects on appropriate receptive-field properties of electrical activation of the midbrain parabrachial region, which is a major nonretinal input to relay cells. Such parabrachial stimulation made each of the eight lagged X cells much more like nonlagged cells, and this stimulation completely transformed the lagged response profiles of six of the eight cells to nonlagged. We thus conclude that the property of lagged responsiveness, which is an emergent property of the lateral geniculate nucleus, is a different response mode of the same cells that can also display nonlagged responses, rather than representing different cell classes; furthermore, this switching between response modes is, at least partly, under the control of afferents from the parabrachial region.

Animals

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.

Animals