Biomedical subjects

S M Sherman

Publications and source records attributed to S M Sherman.

At least 37 records · Page 2Linked to original sources

PubMed1998

Glutamate locally activates dendritic outputs of thalamic interneurons.

The relay of information through thalamus to cortex is dynamically gated, as illustrated by the retinogeniculocortical pathway. Important to this is the inhibitory interneuron in the lateral geniculate nucleus (LGN). For the typical neuron, synaptic information arrives through postsynaptic dendrites and is transmitted by axon terminals. However, the typical thalamic interneuron, in addition to conventional axonal outputs, has distal dendrites that serve both pre- and postsynaptic roles. These dendritic terminals participate in curious and enigmatic triadic arrangements, in which each contacts a relay cell dendrite and is contacted by a glutamatergic retinal terminal that innervates the same relay cell dendrite. Here we show that agonists of the metabotropic glutamate receptor (mGluR) activate dendritic terminals of interneurons in the absence of action potentials, thereby inhibiting the postsynaptic relay neuron. Somatic recordings from LGN interneurons reveal that there is no response to mGluR agonists, suggesting that their dendritic terminals are electrically isolated from their somata and axons, consistent with anatomical modelling of these cells. Our results offer insight into the functioning of triadic circuitry and indicate that thalamic interneurons can perform independent computations expressed through axonal as opposed to dendritic outputs.

Animals↗

PubMed1998

On the actions that one nerve cell can have on another: distinguishing "drivers" from "modulators".

When one nerve cell acts on another, its postsynaptic effect can vary greatly. In sensory systems, inputs from "drivers" can be differentiated from those of "modulators." The driver can be identified as the transmitter of receptive field properties; the modulator can be identified as altering the probability of certain aspects of that transmission. Where receptive fields are not available, the distinction is more difficult and currently is undefined. We use the visual pathways, particularly the thalamic geniculate relay for which much relevant evidence is available, to explore ways in which drivers can be distinguished from modulators. The extent to which the distinction may apply first to other parts of the thalamus and then, possibly, to other parts of the brain is considered. We suggest the following distinctions: Cross-correlograms from driver inputs have sharper peaks than those from modulators; there are likely to be few drivers but many modulators for any one cell; and drivers are likely to act only through ionotropic receptors having a fast postsynaptic effect whereas modulators also are likely to activate metabotropic receptors having a slow and prolonged postsynaptic effect.

Animals↗

PubMed1998

Distribution of synapses in the lateral geniculate nucleus of the cat: differences between laminae A and A1 and between relay cells and interneurons.

Laminae A and A1 of the lateral geniculate nucleus in the cat are generally considered to be a structurally and functionally matched pair of inputs from two eyes, although there are subtle light microscopic and physiological differences. The present study aims to display ultrastructural differences between these two laminae based on electron microscopic observances on the connectivity patterns of their afferents onto two main cell types: relay cells, and interneurons present in this nucleus. In a design of population measurement from randomized sample areas in laminae A and A1 from six brains, all synaptic contacts made by three terminal types of the geniculate nucleus were identified, and a number of relative distribution properties were analyzed. When the A-laminae were considered as a homogeneous structure, the distribution of the three terminal types on geniculate cells was similar to previously reported results, confirming the validity of the sampling strategies used; RLP (retinal) terminals provided one-fifth of all synapses, whereas RD (from cortex and brainstem) and F (inhibitory) types constituted one-half and one-third, respectively. The relay cells alone received a similar composition of afferents. However, interneurons alone received approximately equal amounts of synapses from the three sources. Similar analyses comparing the distributions in lamina A and A1 revealed that RD and F terminals, but not RLP terminals, innervate these two laminae differently; more RD and fewer F terminals were found in lamina A1. This difference was also present in the distribution of terminals on relay cells alone, but not on interneurons. These results suggest that (1) retinal terminals form a significantly larger fraction of the input to interneurons than to relay cells; correspondingly, cortex and brainstem provide a smaller fraction of all inputs to interneurons than to relay cells; and (2) laminae A and A1 are not strictly equivalent projection sites of the two retinae. The results are discussed in relation to the Y-cell subpopulation in lamina A1 that is involved in corticotectal, as well as corticogeniculate circuits, as opposed to Y-cells of lamina A that are involved in only the latter.

Animals↗

PubMed1997

Relative numbers of cortical and brainstem inputs to the lateral geniculate nucleus.

Terminals of a morphological type known as RD (for round vesicles and dense mitochondria, which we define here as the aggregate of types formerly known as RSD and RLD, where "S" is small and "L" is large) constitute at least half of the synaptic inputs to the feline lateral geniculate nucleus, which represents the thalamic relay of retinal input to cortex. It had been thought that the vast majority of these RD terminals were of cortical origin, making the corticogeniculate pathway by far the largest source of input to geniculate relay cells. However, another source of RD terminals recently identified derives from cholinergic cells of the brainstem parabrachial region. (These cells also contain NO.) We used techniques of electron microscopy to determine quantitatively the relative contribution of cortex and brainstem to the population of RD terminals. We identified corticogeniculate terminals by orthograde transport of biocytin injected into the visual cortex and identified brainstem terminals by immunocytochemical labeling for choline acetyltransferase or brain NO synthase (the synthesizing enzymes for acetylcholine and NO, respectively). We estimated the relative numbers of corticogeniculate and brainstem terminals with a two-step algorithm: First, we determined the relative probability of sampling each terminal type in our material, and then we calculated what mixture of identified corticogeniculate and brainstem terminals was needed to recreate the size distribution of the parent RD terminal population. We conclude that brainstem terminals comprise roughly one-half of the RD population. Thus, the cortical input is perhaps half as large and the brainstem input is an order of magnitude larger than had been thought. This further suggests that the brainstem inputs might play a surprisingly complex and subtle role in the control of the geniculocortical relay.

Algorithms↗

PubMed1997

Immunocytochemistry and distribution of parabrachial terminals in the lateral geniculate nucleus of the cat: a comparison with corticogeniculate terminals.

We used immunohistochemistry in cats to demonstrate the presence of brain nitric oxide synthase (BNOS) in cholinergic fibers within the A-laminae of the lateral geniculate nucleus. We used a double labeling procedure with electron microscopy and found that all terminals labeled for choline acetyltransferase (ChAT) in the geniculate A-laminae were double labeled for BNOS. Also, some interneuron dendrites, identified by labeling for gamma-aminobutyric acid (GABA), contained BNOS, but relay cell dendrites did not. We then compared parabrachial and corticogeniculate terminals, identifying the former by BNOS/ChAT labeling and the latter by orthograde transport of biocytin injected into cortical area 17, 18, or 19. All corticogeniculate terminals and most BNOS- or ChAT-positive brainstem terminals displayed RSD morphology, whereas some brainstem terminals exhibited RLD morphology. However, parabrachial terminals were larger, on average, than corticogeniculate terminals. We also found that parabrachial terminals were located both inside and outside of glomeruli, and they always contacted relay cell dendrites proximally among retinal terminals (the retinal recipient zone). In contrast, the cortical terminals were limited to peripheral dendrites (the cortical recipient zone). Thus, little if any overlap exists in the distribution of parabrachial and corticogeniculate terminals on the dendrites of relay cells.

Animals↗

PubMed1997

[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↗

PubMed1996

Ultrastructural localization suggests that retinal and cortical inputs access different metabotropic glutamate receptors in the lateral geniculate nucleus.

Glutamate has an important neuromodulatory role in synaptic transmission through metabotropic glutamate receptors (mGluRs) linked to a variety of G-protein-coupled second messenger pathways. Activation of these receptors on relay cells in the lateral geniculate nucleus (LGN) with the agonist trans-(1S,3R)-1-amino-1, 3-cyclopentanedicarboxylic acid produces a membrane depolarization that inactivates the low-threshold Ca2+ spike, causing a transition from burst to tonic response mode. The excitatory effects of metabotropic receptor activation in the LGN appear to be produced through the receptors linked to phosphoinositide hydrolysis and apparently only through activation of the corticogeniculate pathway. Two mGluRs, mGluR1alpha (a splice variant of mGluR1) and mGluR5, are linked to the phosphoinositide system. We examined the localization of these receptors with affinity-purified, anti-peptide, polyclonal antibodies raised to the C-terminal region of each receptor protein. Under examination with the light microscope, we found that both types of receptors are present in the geniculate neuropil and in that of the overlying thalamic reticular nucleus, including the perigeniculate nucleus. We also examined the ultrastructural localization of immunolabel with the electron microscope, using a postembedding immunogold marker to identify terminals, dendrites, and somata that contain GABA. Label for the antibody directed against mGluR1alpha was primarily localized in the dendrites of relay cells, postsynaptic to various terminal types. Of these, terminal profiles normally associated with corticogeniculate inputs predominated, whereas retinal terminal profiles were scarce. Label for the antibody directed against mGluR5 label was prominent in inhibitory F2-terminal profiles associated with the retinal input to relay cells. In the perigeniculate nucleus, both mGluRs were localized to dendrites. The distribution of the two phosphoinositide-linked mGluRs in the LGN suggests very different functional roles for the two receptor types. We conclude from these data that mGluR1 appears to have a dominant role in corticogeniculate control of response mode through the feedback glutamatergic pathway from layer VI, whereas mGluR5 is positioned to affect retinogeniculate activation of relay cells through feed forward glomerular interactions.

Afferent Pathways↗

PubMed1996

Symptoms of urinary incontinence among older community-dwelling men.

The purpose of this study was to explore the problem of urinary incontinence among elderly men living in the community. Descriptive data from a mailed, 53-item survey were collected and analyzed. The subjects were a convenience sample of 2800 older community-dwelling men enrolled in a hospital-based senior citizens' group in the southwest United States. The 53-item, self-administered survey was designed with a large typeface and a reading level of 3 years of schooling. In pretesting, the instrument required approximately 10 minutes to complete. Within the 2-month response period, 1490 completed surveys were returned for a total response rate of 53%. A subsample of 434 respondents (29%) reported uncontrolled urine leakage of any amount during the month before the survey. Most of these elders reported mild symptoms (84%) or symptoms that had persisted longer than 1 month but less than 2 years (48%). Consistent with the mildness of symptoms reported, the most frequently reported wetness management products were household commodities, such as toilet tissue and paper towels. Only one third of subjects with urinary incontinence symptoms had discussed these symptoms with a physician. Of those who did, almost half received some type of treatment. Incontinence was found to be statistically associated with age, prostate surgery, diuretic use, difficulty in starting urination, and voiding small amounts. In most cases, however, incontinence demonstrated a limited statistical relationship to these variables commonly associated with incontinence. In contrast, caffeine use, a history of prostate problems, and the sensation of incomplete bladder emptying were statistically associated with continence. The prevalence of urinary incontinence among elderly community-dwelling men is significant, although most asserted that their problems with urine loss are mild. In addition to urinary incontinence, many continent and incontinent elderly men have a wide range of urinary dysfunction symptoms.

Aged↗

PubMed1996

Functional organization of thalamocortical relays.

The thalamus has long been seen as responsible for relaying information on the way to the cerebral cortex, but it has not been until the last decade or so that the functional nature of this relay has attracted significant attention. Whereas earlier views tended to relegate thalamic function to a simple, machine-like relay process, recent research, reviewed in this article, demonstrates complicated circuitry and a rich array of membrane properties underlying the thalamic relay. It is now clear that the thalamic relay does not have merely a trivial function. Suggestions that the thalamic circuits and cell properties only come into play during certain phases of sleep to effectively disconnect the relay are correct as far as they go, but they are incomplete, because they fail to take into account interesting and variable properties of the relay that, we argue, occur during normal waking behavior. Although the specific function of the circuits and cellular properties of the thalamic relay for waking behavior is far from clear, we offer two related hypotheses based on recent experimental evidence. One is that the thalamus is not used just to relay peripheral information from, for example, visual, auditory, or cerebellar inputs, but that some thalamic nuclei are arranged instead to relay information from one cortical area to another. The second is that the thalamus is not a simple, passive relay of information to cortex but instead is involved in many dynamic processes that significantly alter the nature of the information relayed to cortex.

Afferent Pathways↗

PubMed1996

Metabotropic glutamate receptors switch visual response mode of lateral geniculate nucleus cells from burst to tonic.

1. Metabotropic glutamate receptors (mGluRs) on relay cells of the lateral geniculate nucleus appear to be activated exclusively by cortical inputs. We thus sought to manipulate these receptors in an effort to gain insight into the possible role of the corticogeniculate pathway. We used in vivo recording and pharmacological techniques in cats to activate or inactivate these receptors on geniculate neurons while analyzing their response properties. 2. Iontophoretic application of the mGluR agonist 1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) to X and Y cells in the geniculate A laminae diminished or abolished burst activity characteristic of low-threshold Ca2+ spikes. This was accompanied by pronounced changes in the visual response, including a decrease in signal detectability as measured with receiver operating characteristic curves. 3. ACPD effects appear specific to mGluRs, because a specific antagonist of ionotropic glutamate receptors (iGluRs) failed to affect the ACPD-evoked responses, and antagonists of ACPD failed to affect iGluR-mediated responses. We found that 3,5-dihydroxyphenylglycine, an agonist reported to be specific for phosphatidylinositol (PI)-linked mGluRs, had effects similar to those of ACPD, implying that these effects are mediated by PI-coupled mGluRs. Furthermore, antagonists reported to be effective against PI-linked mGluRs were effective in antagonizing the ACPD-mediated effects, and substances reported to be agonists to mGluRs coupled to the adenosine 3',5'-cyclic monophosphate cascade did not affect neuronal responses on their own. These data, when added to our preliminary anatomic data, indicate that the receptor responsible for the observed effects may be mGluR1, or a functionally equivalent mGluR. 4. Activation of mGluRs produces changes in geniculate relay cell activity consistent with depolarization of these cells seen during in vitro studies. Such membrane depolarization has been shown to control the activation state of a voltage-dependent Ca2+ conductance, and this, in turn, determines whether the relay cell fires in tonic or burst mode. Our data show that application of ACPD produces a shift in response mode from burst to tonic. Because response mode is an important characteristic of the geniculate relay and because the activation state of certain mGluRs, which helps determine response mode may be controlled by corticogeniculate input, we conclude that an important function of this input is to provide a visuotopically discrete transition from burst to tonic response mode.

Animals↗

PubMed1996

Kinetics of low threshold calcium channels of relay cells in cat lateral geniculate nucleus.

Kinetics of the low threshold T-type Ca2+ channel is studied with single electrode voltage clamp technique on brain slices of the cat lateral geniculate nucleus (LGN). Space clamp is dramatically improved by blocking various K+ and Na+ channels, decreasing Ca2+ current and selecting proper holding potentials. Results from this study are similar to those obtained from acutely dissociated LGN neurons of the rat, indicating that the kinetics of T-Ca2+ channels of the cat LGN neurons is the same as that of the rat LGN. The result reported previously on the cat LGN may result from a defect in space clamp.

Animals↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1994

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↗

PubMed1994

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↗

PubMed1994

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↗

PubMed1993

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↗