Calcium/calmodulin-dependent protein kinase II associates with the K channel isoform Kv4.3 in adult rat optic nerve.

Spikes are said to exhibit "memory" in that they can be altered by spikes that precede them. In retinal ganglion cell axons, for example, rapid spiking can slow the propagation of subsequent spikes. This increases inter-spike interval and, thus, low-pass filters instantaneous spike frequency.

Extraretinal Spike Normalization in Retinal Ganglion Cell Axons.

Spike conduction velocity characteristically differs between myelinated and unmyelinated axons. Here we test whether spikes of myelinated and unmyelinated paths differ in other respects by measuring rat retinal ganglion cell (RGC) spike duration in the intraretinal, unmyelinated nerve fiber layer and the extraretinal, myelinated optic nerve and optic chiasm. We find that rapid spike firing and illumination broaden spikes in intraretinal axons but not in extraretinal axons.

Autophosphorylated CaMKII Facilitates Spike Propagation in Rat Optic Nerve.

Repeated spike firing can transmit information at synapses and modulate spike timing, shape, and conduction velocity. These latter effects have been found to result from voltage-induced changes in ion currents and could alter the signals carried by axons. Here, we test whether Ca/calmodulin-dependent protein kinase II (CaMKII) regulates spike propagation in adult rat optic nerve.

Somatic and neuritic spines on tyrosine hydroxylase-immunopositive cells of rat retina.

Dopamine- and tyrosine hydroxylase-immunopositive cells (TH cells) modulate visually driven signals as they flow through retinal photoreceptor, bipolar, and ganglion cells. Previous studies suggested that TH cells release dopamine from varicose axons arborizing in the inner and outer plexiform layers after glutamatergic synapses depolarize TH cell dendrites in the inner plexiform layer and these depolarizations propagate to the varicosities. Although it has been proposed that these excitatory synapses are formed onto appendages resembling dendritic spines, spines have not been found on TH cells of most species examined to date or on TH cell somata that release dopamine when exposed to glutamate receptor agonists.

Fixation strategies for retinal immunohistochemistry.

Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The beauty of numerous images published to date, and the qualitative and quantitative information they provide, indicate that these approaches are fundamentally useful. However, obtaining these images entailed tissue handling and exposure to chemical solutions that differ from normal extracellular fluid in composition, temperature, and osmolarity.

Moniliform deformation of retinal ganglion cells by formaldehyde-based fixatives.

Protocols for characterizing cellular phenotypes commonly use chemical fixatives to preserve anatomical features, mechanically stabilize tissue, and stop physiological responses. Formaldehyde, diluted in either phosphate-buffered saline or phosphate buffer, has been widely used in studies of neurons, especially in conjunction with dyes and antibodies. However, previous studies have found that these fixatives induce the formation of bead-like varicosities in the dendrites and axons of brain and spinal cord neurons.

Dopamine and full-field illumination activate D1 and D2-D5-type receptors in adult rat retinal ganglion cells.

Dopamine can regulate signal generation and transmission by activating multiple receptors and signaling cascades, especially in striatum, hippocampus, and cerebral cortex. Dopamine modulates an even larger variety of cellular properties in retina, yet has been reported to do so by only D1 receptor-driven cyclic adenosine monophosphate (cAMP) increases or D2 receptor-driven cAMP decreases. Here, we test the possibility that dopamine operates differently on retinal ganglion cells, because the ganglion cell layer binds D1 and D2 receptor ligands, and displays changes in signaling components other than cAMP under illumination that should release dopamine.

Thy1 associates with the cation channel subunit HCN4 in adult rat retina.

Purpose: The membrane expression and gene promoter of the glycosylphosphatidylinositol (GPI)-anchored protein Thy1 have been widely used to examine the morphology and distribution of retinal ganglion cells in normal eyes and disease models. However, it is not known how adult mammalian retinal neurons use Thy1. Because Thy1 is not a membrane-spanning protein and, instead, complexes with structural and signaling proteins in other tissues, the aim of this study was to find protein partners of retinal Thy1.

Colocalization of hyperpolarization-activated, cyclic nucleotide-gated channel subunits in rat retinal ganglion cells.

The current-passing pore of mammalian hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels is formed by subunit isoforms denoted HCN1-4. In various brain areas, antibodies directed against multiple isoforms bind to single neurons, and the current (I(h)) passed during hyperpolarizations differs from that of heterologously expressed homomeric channels. By contrast, retinal rod, cone, and bipolar cells appear to use homomeric HCN channels.

Inhibition of adult rat retinal ganglion cells by D1-type dopamine receptor activation.

The spike output of neural pathways can be regulated by modulating output neuron excitability and/or their synaptic inputs. Dopaminergic interneurons synapse onto cells that route signals to mammalian retinal ganglion cells, but it is unknown whether dopamine can activate receptors in these ganglion cells and, if it does, how this affects their excitability. Here, we show D(1a) receptor-like immunoreactivity in ganglion cells identified in adult rats by retrogradely transported dextran, and that dopamine, D(1)-type receptor agonists, and cAMP analogs inhibit spiking in ganglion cells dissociated from adult rats.

HCN4-like immunoreactivity in rat retinal ganglion cells.

Antisera directed against hyperpolarization-activated, cyclic nucleotide-sensitive (HCN) channels bind to somata in the ganglion cell layer of rat and rabbit retinas, and mRNA for different HCN channel isoforms has been detected in the ganglion cell layer of mouse retina. However, previous studies neither provided evidence that any of the somata are ganglion cells (as opposed to displaced amacrine cells) nor quantified these cells. We therefore tested whether isoform-specific anti-HCN channel antisera bind to ganglion cells labeled by retrograde transport of fluorophore-coupled dextran.

Ih without Kir in adult rat retinal ganglion cells.

Antisera directed against hyperpolarization-activated mixed-cation ("I(h)") and K(+) ("K(ir)") channels bind to some somata in the ganglion cell layer of rat and rabbit retina. Additionally, the termination of hyperpolarizing current injections can trigger spikes in some cat retinal ganglion cells, suggesting a rebound depolarization arising from activation of I(h). However, patch-clamp studies showed that rat ganglion cells lack inward rectification or present an inwardly rectifying K(+) current.

Circuits and properties of signal transmission in the retina.

This essay looks at the historical significance of three APS classic papers that are freely available online: Naka K-I and Nye PW. Role of horizontal cells in organization of the catfish retinal receptive field. J.

DARPP-32-like immunoreactivity in AII amacrine cells of rat retina.

Previous studies demonstrated that the dopamine- and adenosine 3',5'-monophosphate-regulated phosphatase inhibitor known as "DARPP-32" is present in rat, cat, monkey, and human retinas. We have followed up these studies by asking what specific cell subtypes contain DARPP-32. Using a polyclonal antibody directed against a peptide sequence of human DARPP-32, we immunostained adult rat retinas that were either transretinally sectioned or flat mounted and found DARPP-32-like immunoreactivity in some cells of the amacrine cell layer across the entire retinal surface.

Dopamine receptor activation can reduce voltage-gated Na+ current by modulating both entry into and recovery from inactivation.

We tested whether dopamine receptor activation modulates the voltage-gated Na+ current of goldfish retinal ganglion cells, using a fast voltage-clamp amplifier, perforated-patch whole cell mode, and a physiological extracellular Na+ concentration. As found in other cells, activators of D1-type dopamine receptors and of protein kinase A reduced the amplitude of current activated by depolarizations from resting potential without altering the current kinetics or activation range. However, D1-type dopamine receptor activation also accelerated the rate of entry into inactivation during subthreshold depolarizations and slowed the rate of recovery from inactivation after single, brief depolarizations.

Dissociation of retinal ganglion cells without enzymes.

We describe here methods for dissociating retinal ganglion cells from adult goldfish and rat without proteolytic enzymes, and show responses of ganglion cells isolated this way to step-wise voltage changes and fluctuating current injections. Taking advantage of the laminar organization of vertebrate retinas, photoreceptors and other cells were lifted away from the distal side of freshly isolated goldfish retinas, after contact with pieces of membrane filter. Likewise, cells were sliced away from the distal side of freshly isolated rat retinas, after these adhered to a membrane filter.

Availability of low-threshold Ca2+ current in retinal ganglion cells.

Spiking in central neurons depends on the availability of inward and outward currents activated by depolarization and on the activation and priming of currents by hyperpolarization. Of these processes, priming by hyperpolarization is the least described. In the case of T-type Ca2+ current availability, the interplay of hyperpolarization and depolarization has been studied most completely in expression systems, in part because of the difficulty of pharmacologically separating the Ca2+ currents of native neurons.

A single charged surface residue modifies the activity of ikitoxin, a beta-type Na+ channel toxin from Parabuthus transvaalicus.

We previously purified and characterized a peptide toxin, birtoxin, from the South African scorpion Parabuthus transvaalicus. Birtoxin is a 58-residue, long chain neurotoxin that has a unique three disulfide-bridged structure. Here we report the isolation and characterization of ikitoxin, a peptide toxin with a single residue difference, and a markedly reduced biological activity, from birtoxin.