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PubMed1994

Changes in systemic blood pressure and cardiac rhythm induced by therapeutic compression of the trigeminal ganglion.

Percutaneous compression of the trigeminal ganglion, which is currently being used for the control of trigeminal neuralgia, induces marked intraoperative elevations of the systemic blood pressure and heart rate changes, which may increase the risk of cardiovascular complications. We have analyzed the characteristics of the arterial hypertensive response and the cardiac rhythm changes induced by percutaneous compression of the trigeminal ganglion in 42 consecutive, unselected patients undergoing operations for essential trigeminal neuralgia under three different regimens of anesthesia. The first 22 patients (Group 1) underwent operations under brief general anesthesia without endotracheal intubation. The following 10 patients (Group 2) had general anesthesia with intubation and mechanical ventilation and received larger doses of hypnotic and analgesic agents. Finally, 10 more patients (Group 3), who had general anesthesia with intubation, underwent local anesthetic blockade of Meckel's cave (injection of 1 ml of 1% lidocaine) before ganglion compression. Foramen ovale puncture elicited bradycardia in the majority of the patients of Groups 2 and 3, but only four patients (18%) of Group 1 showed bradycardia. Ganglion compression caused marked tachycardia in all patients of Groups 1 and 2; about one-third of the patients also had extrasystoles. By contrast, patients of Group 3, who had local anesthetic blockade of Meckel's cave before ganglion compression, did not develop tachycardia or extrasystoles. Foramen ovale puncture elicited marked elevations of the systemic blood pressure in all patients. Ganglion compression further increased blood pressure, except in patients of Group 3, who had local anesthetic blockade of Meckel's cave.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

The formation of the area centralis of the retinal ganglion cell layer in the chick.

In adult domestic chickens, the neurones in the retinal ganglion cell layer are very unevenly disposed such that there is a sixfold increase in neurone density from the retinal edge to the retinal centre. The formation of the high ganglion-cell-density area centralis was studied on chick retinal wholemounts from the 8th day of incubation (E8) to 4 weeks after hatching (4WAH). The density of viable neurones and the number and the distribution of pyknotic neurones in the ganglion cell layer were estimated across the whole retina. Between E8 and E10, the distribution of neurones in the ganglion cell layer was anisodensitic with 53,000 mm-2 in the centre compared to 34,000 mm-2 in the periphery of the retina. Thereafter, a progressively steeper gradient of neurone density developed, which decreased from 24,000 mm-2 in the retinal centre to 6000 mm-2 at the retinal periphery by 4WAH. Neuronal pyknosis in the ganglion cell layer was observed between E9 and E17. From E11 onwards, consistently more pyknotic neurones were found in the peripheral than in the central retina. It was estimated that over the period of cell death approximately twice as many neurones died per unit area in the retinal periphery than in the centre. Retinal area measurements and estimation of neurone densities in the ganglion cell layer after the period of neurone generation and neurone death indicated differential retinal expansion, with more expansion in the peripheral than in the central retina. These observations allow us to conclude that the formation of the area centralis of the chick retina involves (1) slightly higher cell generation in the retinal centre, (2) higher rate of cell loss in the retinal periphery and (3) differential retinal expansion.

Animals↗
PubMed2005

Voltage-gated sodium channels improve contrast sensitivity of a retinal ganglion cell.

Voltage-gated channels in a retinal ganglion cell are necessary for spike generation. However, they also add noise to the graded potential and spike train of the ganglion cell, which may degrade its contrast sensitivity, and they may also amplify the graded potential signal. We studied the effect of blocking Na+ channels in a ganglion cell on its signal and noise amplitudes and its contrast sensitivity. A spot was flashed at 1-4 Hz over the receptive field center of a brisk transient ganglion cell in an intact mammalian retina maintained in vitro. We measured signal and noise amplitudes from its intracellularly recorded graded potential light response and measured its contrast detection thresholds with an "ideal observer." When Na+ channels in the ganglion cell were blocked with intracellular lidocaine N-ethyl bromide (QX-314), the signal-to-noise ratio (SNR) decreased (p < 0.05) at all tested contrasts (2-100%). Likewise, bath application of tetrodotoxin (TTX) reduced the SNR and contrast sensitivity but only at lower contrasts (< or = 50%), whereas at higher contrasts, it increased the SNR and sensitivity. The opposite effect of TTX at high contrasts suggested involvement of an inhibitory surround mechanism in the inner retina. To test this hypothesis, we blocked glycinergic and GABAergic inputs with strychnine and picrotoxin and found that TTX in this case had the same effect as QX-314: a reduction in the SNR at all contrasts. Noise analysis suggested that blocking Na+ channels with QX-314 or TTX attenuates the amplitude of quantal synaptic voltages. These results demonstrate that Na+ channels in a ganglion cell amplify the synaptic voltage, enhancing the SNR and contrast sensitivity.

Action Potentials↗
PubMed2004

L and M cone contributions to the midget and parasol ganglion cell receptive fields of macaque monkey retina.

Analysis of cone inputs to primate parvocellular ganglion cells suggests that red-green spectral opponency results when connections segregate input from long wavelength (L) or middle wavelength (M) sensitive cones to receptive field centers and surrounds. However, selective circuitry is not an obvious retinal feature. Rather, cone receptive field surrounds and H1 horizontal cells get mixed L and M cone input, likely indiscriminately sampled from the randomly arranged cones of the photoreceptor mosaic. Red-green spectral opponency is consistent with random connections in central retina where the mixed cone ganglion cell surround is opposed by a single cone input to the receptive field center, but not in peripheral retina where centers get multiple cone inputs. The selective and random connection hypotheses might be reconciled if cone type selective circuitry existed in inner retina. If so, the segregation of L and M cone inputs to receptive field centers and surrounds would increase from horizontal to ganglion cell, and opponency would remain strong in peripheral retina. We measured the relative strengths of L and M cone inputs to H1 horizontal cells and parasol and midget ganglion cells by recording intracellular physiological responses from morphologically identified neurons in an in vitro preparation of the macaque monkey retina. The relative strength of L and M cone inputs to H1 and ganglion cells at the same locations matched closely. Peripheral midget cells were nonopponent. These results suggest that peripheral H1 and ganglion cells inherit their L and M cone inputs from the photoreceptor mosaic unmodified by selective circuitry.

Animals↗
PubMed1999

A parasympathetic ganglion innervating the harderian gland and lacrimal gland of the musk shrew (Suncus murinus): fluorescent tracing and immunohistochemical studies.

A small ganglion, named the peri-trigeminal ganglion (PTG), was found in the ventromedial border of the rostral half of the trigeminal ganglion (TG) in the musk shrew (Suncus murinus). In frontal sections, the PTG was semicircular or elliptical in shape. Most of the neurons constituting this ganglion were round in shape and much smaller than those of the TG. The retrograde fluorescent tracer fluoro-gold was injected into various regions of the face in order to investigate innervation by the PTG neurons. When the tracer was injected subcutaneously around the external acoustic meatus and around the circumference of the orbit, a number of labeled neurons were seen not only in the TG but also in the PTG. After applying the tracer to the lacrimal gland (LG) and the harderian gland (HG), numerous labeled neurons were detected only in the PTG. A few labeled neurons were found in the PTG after injection into the palatoglossal arch. Immunohistochemically, most of the neurons constituting the PTG were positive for vasoactive intestinal polypeptide (VIP) antiserum. And a moderate number of somatostatin (SOM)-immunoreactive neurons and a small number of leucine-enkephalin (L-ENK)-immunoreactive neurons were detected. Numerous substance P-immunoreactive nerve fibers and varicosities were found in the PTG, and fewer L-ENK-, SOM- and VIP-immunoreactive fibers were observed. The present results suggest that the PTG is an autonomic ganglion that resembles in part the pterygopalatine ganglion in other species, and mainly innervates the HG and LG.

Animals↗
PubMed1997

Neural interaction in the human spiral ganglion: a TEM study.

A TEM study was performed on freshly fixed human spiral ganglions (HSG) collected during skull base surgery. This technique gives well preserved tissue for ultrastructural analysis. Unlike spiral ganglion cells in mature animals so far studied, most HSG cells lack a myelin coat, but are surrounded by a thin rim of Schwann cell (SC) cytoplasm. In the region of maximal innervation density (upper basal and middle turn), HSG cells were frequently ensheathed by the same Schwann cell, forming a "unit-like" structure. In this region the cells often showed signs of physical interaction where the SCs were frequently incompletely developed ("gaps") so that the cell membranes of adjacent ganglion cells (sometimes as many as four in one section plane) were in direct apposition. In one thin section as many as 20 of 100 ganglion cells were found to face the cell membrane, at any point, of an adjacent cell. At these "gaps" in the SC, complexes of cell membrane specializations occurred between individual HSG cells. The same nerve junctions were also found between unmyelinated nerve fibres and the body of large ganglion cells. Our findings may challenge the view that afferent information in the acoustic nerve is conveyed uninterrupted to the CNS at the level of the spiral ganglion.

Cell Membrane↗
PubMed1987

Reorganization of the peripheral projections of the trigeminal ganglion following neonatal transection of the infraorbital nerve.

Two different anatomical techniques were used to obtain evidence that transection of the infraorbital (IO) nerve on the day of birth would result in reorganization of the peripheral projections of the trigeminal nerve. In 14 of 19 neonatally nerve-damaged adult rats, injection of horseradish peroxidase (HRP) directly into the IO nerve, proximal to the point of the neonatal transection, resulted in labeled cells in the ophthalmic-maxillary portion of the ganglion and labeled fibers in mandibular sensory nerves. In an additional 28 neonatally nerve-damaged adult rats, double-labeling techniques were employed to document the reorganization suggested by the HRP tracing experiments. In these experiments, one fluorescent tracer, diamidino yellow (DY), was injected directly into the regenerate IO nerve, proximal to the point of the neonatal transection; a second tracer, true blue (TB), was deposited into peripheral ophthalmic and/or mandibular fields. These combinations of injections invariably resulted in the demonstration of a small number (46-401) of double-labeled cells that were located in the ophthalmic-maxillary part of the ganglion. Identical combinations of injections in normal adult rats and the intact sides of nerve-damaged animals never produced more than 6 double-labeled cells per ganglion. In two additional series of experiments, sequential double-labeling techniques were employed to demonstrate that the multiply projecting ganglion cells probably arose in at least two ways: (1) development of non-IO projections by ganglion cells that contributed axons to the IO nerve at the time of the lesion; (2) elaboration of IO axon branches by primary afferent neurons that had non-IO projections at the time of the lesion. A final two-stage double-labeling experiment demonstrated that approximately 75% of the ganglion cells that projected to the whisker pad at birth, and survived transection of the IO nerve on the first postnatal day, regenerated axons into this trigeminal branch.

Amidines↗
PubMed1996

Ganglionic neuronal mechanisms involved in circulatory control system.

Intracellular tonic activity and responses to orthodromic stimuli were recorded from the neurones of rabbit superior cervical ganglion and compared with those recorded from the nerves containing pre- and postganglionic nerve fibres, with the use of a coherent recording technique. It was found that: (1) firing of each ganglion neurone is triggered by two presynaptic inputs, single and multiple, formed by a single preganglionic nerve fibre whose discharges evoke the postsynaptic spikes correlated with cardiac rhythm, and by a few converging preganglionic nerve fibres which evoke the postsynaptic spikes, either correlated with cardiac rhythm or irregular, only if two or more of them discharge together, correspondingly; (2) about 240 neurones of the ganglion, on the average, fire synchronously during their tonic activity, being driven by only three preganglionic nerve fibres; (3) only about 9% of a "neural unit", the number of the ganglion neurones receiving innervation from the same preganglionic nerve fibre, are discharged during their tonic activity through a single input, while the rest of neurones are either discharged through a multiple input (17%), or generate only the excitatory postsynaptic potentials subthreshold for spike generation (73%). The results obtained suggest that the ganglionic neuronal mechanisms responsible for vasomotor control involve much more complex ganglionic integrative processes than it has been commonly thought.

Animals↗
PubMed2002

The diversity of ganglion cells in a mammalian retina.

We report a survey of the population of ganglion cells in the rabbit retina. A random sample of 301 neurons in the ganglion cell layer was targeted for photofilling, a method in which the arbors of the chosen neurons are revealed by diffusion of a photochemically induced fluorescent product from their somas. An additional 129 cells were labeled by microinjection of Lucifer yellow. One hundred and thirty-eight cells were visualized by expression of the gene encoding a green fluorescent protein, introduced by particle-mediated gene transfer. One hundred and sixty-six cells were labeled by particle-mediated introduction of DiI. In the total population of 734 neurons, we could identify 11 types of retinal ganglion cell. An analysis based on retinal coverage shows that this number of ganglion cell types would not exceed the available total number of ganglion cells. Although some uncertainties remain, this sample appears to account for the majority of the ganglion cells present in the rabbit retina. Some known physiological types could easily be mapped onto structural types, but half of them could not; a large set of poorly known codings of the visual input is transmitted to the brain.

Animals↗
PubMed1998

[Acupuncture and ganglionic local opioid analgesia in trigeminal neuralgia].

Trigeminal neuralgia (TN) is defined as a chronic, severe, electrifying and burning pain in one side of the face. The attacks are initiated by tactile irritations in a so-called trigger area of the trigeminal nerve and are perceived within the borders of this nerve's innervation. TN is a chronic condition which initially goes into spontaneous remission but these become fewer as the condition progresses. TN is classified as symptomatic when the etiology is known and as idiopathic when the etiology is unknown. There are various forms of treatment: drugs such as anticonvulsants, local ganglionic opioid analgesia (GLOA) at the superior cervical ganglion or sphenopalatine ganglion, percutaneous intervention at the trigeminal ganglion as well as neurosurgery. None of these various procedures has been found to be the most suited and best method. A retrospective analysis of the data of 39 patients who had sought treatment for TN at our pain and acupuncture outpatients' department from 1993 to 1994 was undertaken. Group A (n = 17) had received carbamazepine and acupuncture therapy, group B (n = 11) carbamazepine and GLOA + acupuncture, whereas group C (n = 11) had received carbamazepine and GLOA without acupuncture. All subjects had taken carbamazepine for at least 4 weeks and their plasma levels were within the therapeutic range. Acupuncture therapy was carried out once a week and the number recorded. GLOA was carried out with 0.045 mg buprenorphine at the superior cervical ganglion or the sphenopalatine ganglion as a series of at least 5 injections. The number of attacks of pain and the degree of pain (visual analogue scale [VAS]) were documented. The reduction in pain was categorized in 4 groups: I = pain free, II = reduction of at least 50% on the VAS, III = reduction of less than 50% on the VAS, and IV = no improvement. The statistical analysis was carried out using the chi 2-text, p < 0.05 was considered as significant. Of the groups who received acupuncture as an additive, 8 of the 17 subjects of group A, and 5 of the 11 subjects of group B were pain free, but only 2 of the 11 subjects of group C (no acupuncture). The results of the patients with marked pain reduction (category II) were similar. The most patients with no improvement were from the group which did not receive acupuncture (C). The statistical analysis showed significant differences in the categories I, II, and IV between groups A and C. These results show that the combined use of acupuncture and carbamazepine with/without GLOA achieves an additional therapeutic effect in the treatment of trigeminal neuralgia. The addition of acupuncture seems to have a superior effect to the addition of GLOA. These results support the use of acupuncture as an additional form of therapy for the treatment of trigeminal neuralgia.

Acupuncture Therapy↗
PubMed1999

Pilocarpine toxicity in retinal ganglion cells.

PURPOSE: Muscarinic agents reduce intraocular pressure by enhancing aqueous outflow, probably by stimulating ciliary muscle contraction. However, pilocarpine is a well characterized neurotoxin and is widely used to generate animal seizure models. It was therefore investigated whether pilocarpine was also toxic to retinal ganglion cells. METHODS: Dissociated whole retinal preparations were prepared from postnatal day 16 to 19 rats. Retinal ganglion cells had been previously back-labeled with a fluorescent tracer. Retinal cells were incubated with pilocarpine, lithium, and inositol derivatives, and viability of the retrogradely labeled retinal ganglion cells was assayed after 24 hours. RESULTS: Pilocarpine was toxic to retinal ganglion cells in a dose-dependent fashion. This toxicity was potentiated by lithium and blocked by epi- and myo-inositol. CONCLUSIONS: Pilocarpine is toxic to retinal ganglion cells in a mixed culture assay. This toxicity appears to depend on the inositol pathway and is similar to its mode of action in other neurons. However, 0.4 mM pilocarpine (the lowest concentration that did not affect ganglion cell survival) is roughly 1000-fold higher than the vitreal concentration and 20-fold higher than the scleral concentration that can be obtained with topical administration of 2% pilocarpine in the rabbit eye.

Animals↗
PubMed1999

Experimental induction of retinal ganglion cell death in adult mice.

PURPOSE: Retinal ganglion cells die by apoptosis during development and after trauma such as axonal damage and exposure to excitotoxins. Apoptosis is associated with changes in the expression of genes that regulate this process. The genes that regulate apoptosis in retinal ganglion cells have not been characterized primarily because previous studies have been limited to animal models in which gene function is not easily manipulated. To overcome this limitation, the rate and mechanism of retinal ganglion cell death in mice was characterized using optic nerve crush and intravitreal injections of the glutamate analog N-methyl-D-aspartate (NMDA). METHODS: To expose retinal ganglion cells (RGCs) to excitotoxins, adult CB6F1 mice were injected intravitreally in one eye with NMDA. In an alternative protocol to physically damage the axons in the optic nerve, the nerve was crushed using self-closing fine forceps. Each animal had one or the other procedure carried out on one eye. Loss of RGCs was monitored as a percentage of cells lost relative to the fellow untreated eye. Thy1 expression was examined using in situ hybridization. DNA fragmentation in dying cells was monitored using terminal transferase-dUTP nick-end labeling (TUNEL). RESULTS: RGCs comprise 67.5% +/- 6.5% (mean +/- SD) of cells in the ganglion cell layer (GCL) of control mice based on nuclear morphology and the presence of mRNA for the ganglion cell marker Thy1. One week after optic nerve crush, these cells started to die, progressing to a maximum loss of 57.8% +/- 8.1% of the cells in the GCL by 3 weeks. Cell loss after NMDA injection was dose dependent, with injections of 10 nanomoles having virtually no effect to a maximum loss of 72.5% +/- 12.1% of the cells in the GCL within 6 days after injection of 160 nanomoles NMDA. Cell death exhibited features of apoptosis after both optic nerve crush and NMDA injection, including the formation of pyknotic nuclei and TUNEL staining. CONCLUSIONS: Quantitative RGC death can be induced in mice using two distinct signaling pathways, making it possible to test the roles of genes in this process using transgenic animals.

Animals↗
PubMed1999

Assessment of Thy-1 mRNA levels as an index of retinal ganglion cell damage.

PURPOSE: Thy-1 is primarily, if not entirely, expressed by the ganglion cells within the retina. This knowledge was used to index ganglion cell death after ischemia and excitotoxicity by studying changes in Thy-1 mRNA levels. METHODS: Insults to the rat retina were delivered either by elevation of intraocular pressure for 60 minutes or by intravitreal injection of N-methyl-D-aspartate (NMDA). After a defined period, changes in Thy-1 immunoreactivity and mRNA levels of Thy-1 and NR1 (NMDA receptor subunit) were used to index ganglion cell sensitivity to damage. Opsin mRNA levels were used as an internal control because photoreceptors lack NMDA receptors. RESULTS: Retinal Thy-1 immunoreactivity, associated with the ganglion cell and inner plexiform layers, is reduced by ischemia or intravitreal injections of NMDA in a dose-dependent manner. Using a semi-quantitative polymerase chain reaction (reverse transcription-polymerase chain reaction) methodology, the levels of total retinal Thy-1 and NR1 mRNAs were shown to be dramatically reduced after both transient ischemia and intravitreal injection of NMDA. The effect of NMDA was found to be both time- and dose-dependent. In contrast, no change occurred in the levels of opsin mRNA unless high levels of NMDA (200 nmoles) were administered. CONCLUSIONS: Ischemia and NMDA-induced excitotoxicity caused retinal ganglion cell destruction, but the photoreceptors were unaffected. Measurement of total retinal Thy-1 mRNA levels provides a useful way of following ganglion cell death especially when combined with immunohistochemical localization of Thy-1. Additionally, the effect on other retinal cell types such as the photoreceptors can be followed in concert using this technique.

Animals↗
PubMed2000

Retinal ganglion cells in the South American opossum (Didelphis aurita).

By using the Golgi technique, the authors investigated the morphology of ganglion cells in the retinas of South American opossums. In flat-mount preparations of the retinas, cell bodies, entire dendritic fields, and the stratification level of ganglion cells were studied. Fractal dimensions of dendritic trees, an objective quantitative measure of morphological complexity, were included as a morphological parameter of classification. Based on these characteristics, nineteen types of ganglion cells were described. A great number of opossum ganglion cell types had dendrites stratifying in both sublaminae of the inner plexiform layer (IPL) in five different ways (S1-S3 [G9], S1-S4 [G17 and G22], S2/S3 [G19], S2-S4 [G15, G16, G21 and G221, and S2-S5 [G61), and only two types (G8, and G10) showed narrow field dendritic trees ramifying in S4 only. Morphological types of opossum ganglion cells were compared to their counterparts in cat retina. The distribution pattern of large cell bodies on the ganglion cell layer was analyzed employing the Nissl staining method, immunocytochemistry for neurofilaments, and the reduced silver neurofibrillar staining method. The results showed a random pattern of distribution.

Animals↗
PubMed2000

Development of ganglion cell topography in the postnatal cochlea.

In mammals, the size and number of spiral ganglion cells can vary significantly along the length of the cochlea. At present, it is unclear how these topologic differences in spiral ganglion cell morphology and density emerge during development. We addressed this issue by quantifying developmental changes in the number, density, and size of auditory ganglion cells within the cochlea of Mongolian gerbils throughout the first 3 weeks of postnatal life. In each cochlea, cells were measured at five standardized locations along the length of the spiral ganglion, as determined from serial reconstruction of Rosenthal's canal. During the first postnatal week, the total number of gerbil spiral ganglion cells decreased significantly by 27%, without further change thereafter. This brief period of neuronal cell death coincides with a major remodeling in the afferent neural projections to gerbil auditory hair cells (Echteler [1992] Proc. Natl. Acad. Sci. USA 89:6324-6327). The resulting reduction in neuronal density varied with location, being most prominent within the upper basal and lower middle turns of the cochlea. These same regions contained the smallest auditory ganglion cells found within the gerbil ear and exhibited the least amount of developmental expansion in the circumference of Rosenthal's canal. These results suggest the possibility that regional differences in auditory neuron size and number might be influenced by local extrinsic factors, such as the availability of canal space.

Aging↗
PubMed2000

Increased production of tumor necrosis factor-alpha by glial cells exposed to simulated ischemia or elevated hydrostatic pressure induces apoptosis in cocultured retinal ganglion cells.

Although glial cells in the optic nerve head undergo a reactivation process in glaucoma, the role of glial cells during glaucomatous neurodegeneration of retinal ganglion cells is unknown. Using a coculture system in which retinal ganglion cells and glial cells are grown on different layers but share the same culture medium, we studied the influences of glial cells on survival of retinal ganglion cells after exposure to different stress conditions typified by simulated ischemia and elevated hydrostatic pressure. After the exposure to these stressors, we observed that glial cells secreted tumor necrosis factor-alpha (TNF-alpha) as well as other noxious agents such as nitric oxide into the coculture media and facilitated the apoptotic death of retinal ganglion cells as assessed by morphology, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and caspase activity. The glial origin of these noxious effects was confirmed by passive transfer experiments. Furthermore, retinal ganglion cell apoptosis was attenuated approximately 66% by a neutralizing antibody against TNF-alpha and 50% by a selective inhibitor of inducible nitric oxide synthase (1400W). Because elevated intraocular pressure and ischemia are two prominent stress factors identified in the eyes of patients with glaucoma, these findings reveal a novel glia-initiated pathogenic mechanism for retinal ganglion cell death in glaucoma. In addition, these findings suggest that the inhibition of TNF-alpha that is released by reactivated glial cells may provide a novel therapeutic target for neuroprotection in the treatment of glaucomatous optic neuropathy.

Animals↗
PubMed2001

Synaptic currents generating the inhibitory surround of ganglion cells in the mammalian retina.

The receptive field (RF) of retinal ganglion cells (RGCs) consists of an excitatory central region, the RF center, and an inhibitory peripheral region, the RF surround. It is still unknown in detail which inhibitory interneurons (horizontal or amacrine cells) and which inhibitory circuits (presynaptic or postsynaptic) generate the RF surround. To study surround inhibition, light-evoked whole-cell currents were recorded from RGCs of the isolated, intact rabbit retina. The RFs were stimulated with light or dark spots of increasing diameters and with annular light stimuli. Direct inhibitory currents could be isolated by voltage clamping ganglion cells close to the Na(+)/K(+) reversal potential. They mostly represent an input from GABAergic amacrine cells that contribute to the inhibitory surround of ganglion cells. This direct inhibitory input and its physiological function were also investigated by recording light-evoked action potentials of RGCs in the current-clamp mode and by changing the intracellular Cl(-) concentration. The excitatory input of the ganglion cells could be isolated by voltage clamping ganglion cells at the Cl(-) reversal potential. Large light spots and annular light stimuli caused a strong attenuation of the excitatory input. Both GABA(A) receptors and GABA(C) receptors contributed to this inhibition, and picrotoxinin was able to completely block it. Together, these results show that the RF surround of retinal ganglion cells is mediated by a combination of direct inhibitory synapses and presynaptic surround inhibition.

Action Potentials↗
PubMed2002

Increased spontaneous retinal ganglion cell activity in rd mice after neural retinal transplantation.

PURPOSE: To study the functional success of neural retinal transplantation by means of retinal surface ganglion cell recordings. METHODS: Eight-week-old C3H/HeJ (rd/rd) retinal degeneration mice received transplants (subretinal) in one eye only of neural retinal tissue isolated from newborn normal C57/BL6J mice. Four weeks after transplantation, ganglion cell responses were recorded directly from the retinal surface over the transplant, with a differential bipolar surface electrode. Measurements were performed, both with and without light stimulation. Similar recordings were performed in nontransplant areas of the transplant-recipient eyes, and in age-matched sham-treated and untreated control eyes. After the recordings, the eyes were processed for light and transmission electron microscopy. RESULTS: Histologic examination showed that in some areas, transplanted cells were organized into small sheets and differentiated into photoreceptors with outer segments in intimate contact with the host RPE. No light-driven ganglion cell responses were recordable from the transplant-recipient or control eyes. However, the spontaneous ganglion cell activity was higher in the transplant areas (mean: 10.8 +/-12.0 spikes/1.6 sec) compared with nontransplant areas of these recipient eyes (mean: 2.4 +/- 5.7spikes/1.6 sec; P < 0.001), sham-treated eyes (mean: 2.5 +/- 4.8 spikes/1.6 sec; P < 0.001), and the untreated control eyes (mean: 2.2 +/- 4.4 spikes/1.6 sec; P < 0.001). CONCLUSIONS: Subretinal transplantation of neural retinal tissue results in a local increase of spontaneous ganglion cell activity. The increased activity may be due to the release of neurochemically active substances as a result of the presence of the transplant. Although light responses were not recordable, the technique of retinal surface ganglion cell recording may be useful for assessing the functional success of transplantation.

Action Potentials↗