bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential expression of K+ currents in mammalian
retinal bipolar cells
Authors: HU HUI-JUAN , PAN ZHUO-HUA
Published: December 2002

Whole-cell voltage-clamp recordings were performed to investigate
voltage-dependent K+ currents in acutely isolated
retinal cone bipolar cells (CBCs) from the rat. The physiological
and pharmacological properties of the currents were compared
with those in rod bipolar cells (RBCs). The K+ currents
were found to be much larger in CBC than in RBCs. In addition,
the currents in CBCs were activated and inactivated at more
negative potentials. Based on the apparent inactivation property
of the currents, CBCs were found to fall into two groups of cells
that differed in the inactivation kinetics of IK(V)
but did not correlate to the ON- and OFF-type. The IK(V)
for the group of CBCs showing faster inactivation, as well as for all RBCs,
contained two components with decay time constants around 0.1 and 1 s. The
IK(V) for the group of CBCs showing slower inactivation
only contained the slower component. Furthermore, three components of
IK(V) were observed based on tetraethylammonium
(TEA) sensitivity: high-sensitive, low-sensitive, and resistant
component. The IK(V) for a portion of CBCs showing
faster inactivation, as well as for all RBCs, contained all three components.
The IK(V) for the remaining CBCs, including all
of those CBCs showing slower inactivation, only contained the
latter two components. This study reveals a differential expression
of K+ currents in rat retinal bipolar cells, suggesting
that K+ channels may play an important role in bipolar
cell processing in mammalian retinas.
Alpha-2 adrenoceptor agonist protects retinal function after
acute retinal ischemic injury in the rat
Authors: LAI RONALD K. , CHUN TERESA , HASSON DAIN , LEE STEVE , MEHRBOD FARROKH , WHEELER LARRY
Published: December 2002

Alpha-2 adrenoceptor agonists have previously been shown to
enhance neuronal survival in an optic nerve mechanical injury
model and to protect photoreceptors in a light-induced degeneration
model. The purpose of this study was to examine the effect of
the alpha-2 adrenoceptor agonist in a pressure-induced retinal
ischemia model. Brown-Norway rats were treated systemically
or topically with alpha-2 adrenoceptor specific agonist
brimonidine. Retinal ischemia was induced by increasing the
intraocular pressure to 110 mm Hg for 50 min. The effect of
brimonidine on retinal ischemic injury was functionally assessed
in the rats 7 d later using electroretinography (ERG).
Ischemia-induced retinal cell death was studied using the terminal
deoxynucleotidyl transferase-mediated dUTP nick end-labeling
(TUNEL) staining. We found that brimonidine treatment significantly
protected the retina from retinal ischemic injury in a dose-
and time-dependent manner. This protection can be achieved either
by systemic or topical application and can be blocked by
pretreatment with the alpha-2 adrenoceptor antagonist, yohimbine.
Using reverse transcription-polymerase chain reaction (RT-PCR)
and Western blot analysis, we found that brimonidine can
up-regulate the expression of basic fibroblast growth factor,
bcl-2 and bcl-xl in the retina. The drug also can activate two
major cell survival signaling pathways in the retina: the
extracellular-signal-regulated kinases (ERKs) and
phosphatidylinositol-3′ kinase/protein kinase Akt pathways.
All these aforementioned factors may potentially contribute
in mediating brimonidine's protective effect in this acute
retinal ischemia model.
The functional organization of area V2, I: Specialization
across stripes and layers
Authors: SHIPP STEWART , ZEKI SEMIR
Published: December 2002

We used qualitative tests to assess the sensitivity of 1043
V2 neurons (predominantly multiunits) in anesthetised macaque
monkeys to direction, length, orientation, and color of moving
bar stimuli. Spectral sensitivity was additionally tested by
noting ON or OFF responses to flashed stimuli of varied size
and color. The location of 649 units was identified with respect
to cycles of cytochrome oxidase stripes (thick-inter-thin-inter)
and cortical layer. We used an initial 8-way stripe classification
(4 stripes, and 4 “marginal” zones at interstripes
boundaries), and a 9-way layer classification (5 standard layers
(2–6), and 4 “marginal” strata at layer
boundaries). These classes were collapsed differently for
particular analyses of functional distribution; the main
stripe-by-layer analysis was performed on 18 compartments (3
stripes × 6 layers). We found direction sensitivity only
within thick stripes, orientation sensitivity mainly in thick
stripes and interstripes, and spectral sensitivity mainly in
thin stripes. Positive length summation was relatively more
frequent in thick stripes and interstripes, and negative
length/size summation in thin stripes. All these
“majority” characteristics of stripes were most
prominent in layers 3A and 3B. By contrast, “minority”
characteristics (e.g. spectral sensitivity in thick stripes;
positive size summation in thin stripes) tended to be most frequent
in the outer layers, that is, layers 2 and 6. In consequence,
going by the four functions tested, the distinctions between
stripes were maximal in layer 3, moderate in layer 2, and minimal
in layer 6.
The functional organization of area V2, II: The impact of
stripes on visual topography
Authors: SHIPP STEWART , ZEKI SEMIR
Published: December 2002

We have examined the visuotopic organization of area V2 of
macaque monkeys in relation to its modular construction, comprising
repetitive cycles of stripes running perpendicular to the border
with area V1. Receptive fields were plotted in anesthetised
animals, mainly using long penetrations parallel to the V1 border
crossing several stripes in dorsal V2 within the representation
of paracentral, inferior visual field. We confirm that each
set of modules (thick, thin, and interstripes) mounts an unbroken
coverage of the visual field, since there is almost invariably
some overlap between the aggregate fields recorded in successive
stripes of the same class, at intervals of one cycle. Also as
expected, penetrations perpendicular to the stripes record changes
in eccentricity along an isopolar visual meridian. We measured
the size of the point image along such an isopolar meridian
in nine cases, and showed that on average it exceeds the length
of a typical cycle; again, this implies that no point in space
escapes analysis by any of the functional modules. The
representation of eccentricity across a cycle of stripes resembles
a “ratchet” model, in which the gradient of
eccentricity across a single stripe exceeds the gradient across
the full cycle, leading to discontinuities
(“switchbacks”) at the borders between stripes.
The shift in eccentricity across the width of a stripe is
sufficient to maintain a virtually continuous map across successive
stripes of the same class; when coupled to receptive field scatter
about the mean trend, this creates the overlap of aggregate fields.
D2-like dopamine receptors promote interactions
between calcium and chloride channels that diminish rod synaptic
transfer in the salamander retina
Authors: THORESON WALLACE B. , STELLA SALVATORE L. , BRYSON ERIC J. , CLEMENTS JOHN , WITKOVSKY PAUL
Published: December 2002

Activation of D2-like dopamine receptors in rods with
quinpirole stimulates L-type calcium currents (ICa).
This result appears inconsistent with studies showing that
D2-like dopamine receptor activation diminishes rod
signals in second-order retinal neurons. Since small reductions in
[Cl−]i can inhibit
photoreceptor ICa, we tested the hypothesis that
enhancement of ICa with the D2/D4
receptor agonist, quinpirole, increases calcium-activated chloride
currents (ICl(Ca)) causing an efflux of
Cl− from rods that would provide a negative feedback
inhibition of ICa. In agreement with studies from
Xenopus, quinpirole reduced rod input to second-order neurons
of tiger salamander retina without significantly altering rod voltage
responses. Quinpirole also diminished the amplitude of
depolarization-evoked increases in [Ca2+]i
measured with Fura-2 in rods, a finding consistent with inhibition of
synaptic transmission from rods. Electrophysiological and
Cl−-imaging experiments indicated ECl
in rods is ∼ −20 mV. Quinpirole enhanced ICl(Ca)
and elicited an efflux of Cl− at the resting
potential. A similar Cl− efflux was produced
by extracellular replacement of 24 mM Cl− with
CH3SO4− and this low
Cl− solution inhibited Ca2+responses
to a similar degree as quinpirole did. When ICl(Ca)
was inhibited with niflumic acid, quinpirole enhanced both
ICa and depolarization-evoked increases in
[Ca2+]i. Furthermore, with niflumic
acid, quinpirole no longer inhibited rod inputs into horizontal and
bipolar cells. These results suggest an initial enhancement of
ICa by quinpirole is followed by a stimulation of
Cl− currents, including ICl(Ca).
The net result is a Cl− efflux that inhibits
depolarization-evoked increases in [Ca2+]i
and synaptic transmission from rods.
NMDA-evoked [Ca2+]i increase
in salamander retinal ganglion cells: Modulation by PKA and
adrenergic receptors
Authors: HAN YI , WU SAMUEL M.
Published: December 2002

Application of NMDA induces a depolarization and increase of
intracellular calcium concentration
([Ca2+]i) in retinal ganglion
cells, which cause ganglion cell death in models of glaucoma.
In the present study, we investigated the pharmacological mechanism
of how NMDA-evoked increase in calcium could be modulated in
dissociated retinal ganglion cells from tiger salamander. In
these neurons, protein kinase A (PKA) up-regulated the NMDA-evoked
[Ca2+]i increase. In the presence
of 8-bromo-cAMP or forskolin to stimulate PKA, the elevation
level of [Ca2+]i induced by
NMDA became even higher; In the presence of H-89, a PKA inhibitor, the
NMDA-evoked [Ca2+]i increase was
attenuated. In addition, applications of adrenergic compounds were also
found to influence the NMDA-evoked [Ca2+]i
increase. UK-14,304, a selective α2 agonist, reduced the
elevation level of [Ca2+]i caused by NMDA.
In contrast, isoproterenol, a β agonist, augmented the NMDA-evoked
[Ca2+]i increase. These adrenergic
regulations were due to direct activation of adrenoceptors, since
modulations of both UK-14,304 and isoproterenol on the NMDA-evoked
[Ca2+]i increase were abolished by
their respective antagonists. Furthermore, adrenergic regulations were
mediated through a PKA-related pathway since PKA inhibitor blocked
adrenergic regulations. The possible modulatory site(s) by PKA was also
discussed.
Transgenic expression of a GFP-rhodopsin COOH-terminal fusion
protein in zebrafish rod photoreceptors
Authors: PERKINS BRIAN D. , KAINZ PAMELA M. , O'MALLEY DONALD M. , DOWLING JOHN E.
Published: December 2002

To facilitate the identification and characterization of mutations
affecting the retina and photoreceptors in the zebrafish, a
transgene expressing green fluorescent protein (GFP) fused to
the C-terminal 44 amino acids of Xenopus rhodopsin
(Tam et al., 2000) under the control of the 1.3-kb proximal
Xenopus opsin promoter was inserted into the zebrafish
genome. GFP expression was easily observed in a ventral patch
of retinal cells at 4 days postfertilization (dpf). Between
45–50% of the progeny from the F1, F2, and F3 generations
expressed the transgene, consistent with a single integration
event following microinjection. Immunohistochemical analysis
demonstrated that GFP is expressed exclusively in rod
photoreceptors and not in the UV, blue, or red/green double
cones. Furthermore, GFP is localized to the rod outer segments
with little to no fluorescence in the rod inner segments, rod
cell bodies, or rod synapse regions, indicating proper targeting
and transport of the GFP fusion protein. Application of exogenous
retinoic acid (RA) increased the number of GFP-expressing cells
throughout the retina, and possibly the level of expressed
rhodopsin. When bred to a zebrafish rod degeneration mutant,
fewer GFP-expressing rods were seen in living mutants as compared
to wild-type siblings. This transgenic line will facilitate
the search for recessive and dominant mutations affecting rod
photoreceptor development and survival as well as proper rhodopsin
expression, targeting, and transport.
Melatonin receptor mRNA localization and rhythmicity in the
retina of the domestic chick, Gallus domesticus
Authors: NATESAN ARJUN K. , CASSONE VINCENT M.
Published: December 2002

The indoleamine hormone melatonin is synthesized and released
by photoreceptors during the night within the chick retina,
and confers timing information to modulate retinal physiology.
Three subtypes of melatonin receptor with nearly identical
pharmacological profiles have been described in chickens and
are present in the retina. In this study, the spatial localization
and temporal pattern of the mRNA for each of these receptors
within the retina are described. The localization and rhythmicity
of receptor mRNA were analyzed using in situ hybridization
and RNase protection assay, respectively, with probes against
specific nucleotide sequences encoding these receptors.
Mel1A and Mel1C receptor mRNA have similar
patterns of expression, primarily in the inner segments of
photoreceptors, vitread portion of the inner nuclear layer,
and in the retinal ganglion cell layer. Mel1B receptor
mRNA is expressed at higher levels in the retina, with expression
in photoreceptors, throughout the inner nuclear layer, and in
the ganglion cell layer. Mel1A receptor mRNA is rhythmic
in both light:dark (LD) cycles and in constant darkness (DD);
Mel1A peaks during midday and mid-subjective day,
respectively. Mel1C receptor mRNA is also rhythmically
expressed in LD, but with a lower amplitude, such that transcript
is high during the day and low during the night. In DD,
Mel1C rhythms become 180 deg out of phase with a
slight increase at night. Mel1B mRNA expression was
highly variable and arrhythmic.
Activation of group II metabotropic glutamate receptors inhibits
glutamate release from salamander retinal photoreceptors
Authors: HIGGS MATTHEW H. , LUKASIEWICZ PETER D.
Published: December 2002

We investigated the effects of group II metabotropic glutamate
receptor (mGluR) activation on excitatory synaptic transmission
in the salamander retinal slice preparation. The group II selective
agonists DCG-IV and LY354740 reduced light-evoked excitatory
postsynaptic currents (EPSCs) in ganglion cells. To determine
the synaptic basis of this effect, we also recorded from bipolar
cells and horizontal cells. In ON bipolar cells, DCG-IV increased
the inward current in darkness but did not affect the peak current
at light onset. In OFF bipolar cells and horizontal cells, DCG-IV
had the opposite effect, reducing the inward current in darkness.
Given the opposite polarities of these two classes of synapses,
our results suggest that group II mGluRs act presynaptically
to reduce glutamate release from photoreceptors. To determine
whether DCG-IV affected rods or cones, we applied light stimuli
that selectively activate each type of photoreceptor. In horizontal
cells, most of which receive mixed synaptic input from rods
and cones, DCG-IV reduced rod-driven EPSCs evoked by 470-nm
stimuli and cone-driven EPSCs elicited by 700-nm stimuli in
the presence of a rod-saturating background. Thus, activation
of group II mGluRs reduced rod- and cone-mediated glutamate
release. Our results suggest that group II mGluRs could mediate
feedback by which extracellular glutamate inhibits glutamate
release from photoreceptor terminals.
Central regulation of photosensitive membrane turnover in
the lateral eye of Limulus. I. Octopamine primes the
retina for daily transient rhabdom shedding
Authors: KHADILKAR RASHMI V. , MYTINGER JOHN R. , THOMASON LAURA E. , RUNYON SCOTT L. , WASHICOSKY KEVIN J. , JINKS ROBERT N.
Published: December 2002

Limulus lateral eyes shed and renew a portion of their
photosensitive membrane (rhabdom) daily. Shedding, in many species
including Limulus, is regulated by complex interactions
between circadian rhythms and light. Little is known about how
circadian clocks and photoreceptors communicate to regulate
shedding. Limulus photoreceptors do not contain an
endogenous circadian oscillator, but rely upon efferent outflow
from a central clock for circadian timing. To investigate whether
the putative efferent neurotransmitter octopamine (OA) communicates
circadian rhythms that prime the lateral eye for transient rhabdom
shedding, we decoupled photoreceptors from the clock by transecting
the lateral optic nerve (contains the retinal efferent fibers).
Overnight (6 h) intraretinal injections of 40 μM OA restored
transient shedding to lateral eyes with transected nerves to
levels comparable to those of intact internal control eyes.
To determine whether OA acts alone in communicating circadian
rhythms that prime the lateral eye for transient shedding, we
“primed” eyes with intact nerves for transient shedding
with exogenous OA during subjective day. In nature, lateral
eyes shed their rhabdoms only once a day at dawn following
overnight efferent priming. Eyes in animals placed in darkness
during subjective day, when the retinal efferents are quiescent,
and injected for 6 h with 40 μM OA shed their rhabdoms in
response to a second introduction to light. Untreated control
eyes of the same animals did not. The same results were observed
in vitro in lateral eyes treated similarly. Octopamine
is the only efferent neurotransmitter/messenger required to
make lateral eyes competent for transient shedding. Phentolamine,
an OA receptor antagonist, reduced the number of photoreceptors
primed for transient shedding and the amount of rhabdom shed
in those photoreceptors suggesting that OA acts via
a specific OA receptor.
Synaptic input to an ON parasol ganglion cell in the macaque
retina: A serial section analysis
Authors: MARSHAK DAVID W. , YAMADA ELIZABETH S. , BORDT ANDREA S. , PERRYMAN WENDY C.
Published: December 2002

A labeled ON parasol ganglion cell from a macaque retina was
analyzed in serial, ultrathin sections. It received 13% of its
input from diffuse bipolar cells. These directed a large proportion
of their output to amacrine cells but received a relatively
small proportion of their amacrine cell input via feedback
synapses. In these respects, they were similar to the DB3 bipolar
cells that make synapses onto OFF parasol cells. Bipolar cell
axons that contacted the ON parasol cell in stratum 4 of the
inner plexiform layer always made synapses onto the dendrite,
and therefore, the number of bipolar cell synapses onto these
ganglion cells could be estimated reliably by light microscopy
in the future. Amacrine cells provided the majority of inputs
to the ON parasol cell. Only a few of the presynaptic amacrine
cell processes received inputs from the same bipolar cells as
the parasol cells, and most of the presynaptic amacrine cell
processes did not receive any inputs at all within the series.
These findings suggest that most of the inhibitory input to
the ON parasol cell originates from other areas of the retina.
Amacrine cells presynaptic to the parasol ganglion cell interacted
very infrequently with other neurons in the circuit, and therefore,
they would be expected to act independently, for the most part.
Distribution and origin of the catecholaminergic innervation
in the amphibian mesencephalic tectum
Authors: SÁNCHEZ-CAMACHO CRISTINA , MARÍN OSCAR , GONZÁLEZ AGUSTÍN
Published: December 2002

The mesencephalic tectum plays a prominent role in integrating
both visual and multimodal sensory information essential for
normal behavior in amphibians. Activity in the mesencephalic
tectum is thought to be modulated by the influence of distinct
neurochemical inputs, including the catecholaminergic and the
cholinergic systems. In the present study, we have investigated
the distribution and the origin of the catecholaminergic
innervation of the mesencephalic tectum in two amphibian species,
the anuran Rana perezi and the urodele Pleurodeles
waltl. Immunohistochemistry for dopamine and two enzymes
required for the synthesis of catecholamines, tyrosine hydroxylase
(TH) and dopamine β-hydroxylase (DBH), revealed a complex
pattern of catecholaminergic (CA) innervation in the anuran
and urodele mesencephalic tectum. Dopaminergic fibers were
primarily present in deep tectal layers, whereas noradrenergic
(DBH immunoreactive) fibers predominated in superficial layers.
Catecholaminergic cell bodies were never observed within the
tectum. To determine the origin of this innervation, applications
of retrograde tracers into the optic tectum were combined with
immunohistochemistry for TH. Results from these experiments
demonstrate that dopaminergic neurons in the suprachiasmatic
and juxtacommissural nuclei (in Rana) or in the nucleus
pretectalis (in Pleurodeles), together with noradrenergic
cells of the locus coeruleus, are the sources of CA input to
the amphibian mesencephalic tectum. The present results suggest
that similar CA modulatory inputs are present in the
mesecencephalic tectum of both anurans and urodeles.
Effects of surround motion on receptive-field gain and structure
in area 17 of the cat
Authors: PALMER LARRY.A. , NAFZIGER JOHN.S.
Published: December 2002

Modulation of responses elicited by moving bars within the
classical receptive fields (CRF) of cat area 17 neurons were
studied as a function of the direction and velocity of drifting
gratings in the surrounds. Several different types of modulation
were observed; collectively, the responses of most cells, both
simple and complex, were strongly modulated by surround motion.
None of these cells appear to signal relative velocity between
the CRF and its surround. The gain and spatiotemporal structure
of the CRF mechanism were estimated using contrast-response
functions and reverse correlation with spatiotemporal ternary
white noise, respectively. These measurements were made in the
presence of surround gratings shown to significantly modify
responses elicited from the CRF. In all cases, the gain of the
CRF mechanism was driven up or down relative to controls but
the receptive-field structure did not change in any way. We
conclude that neurons in cat area 17 act like scalable filters,
meaning that their gains can be adjusted by stimuli in the
surrounds without altering the properties of the CRF. This was
verified by showing that velocity tuning curves were also
unmodified by stimuli in the surround that did change the gain.
Based in part on these data, we discuss the notion that primary
visual cortex makes use of a double-opponent mechanism for the
representation of local discontinuities in motion and orientation.
Mapping absorbance spectra, cone fractions, and neuronal
mechanisms to photopic spectral sensitivity in the zebrafish
Authors: CAMERON DAVID A.
Published: December 2002

The four spectral cone types in the zebrafish retina each
contribute to photopic visual sensitivity as measured by the
b-wave of the electroretinogram (ERG). The goal of
the current study was to evaluate a model of photopic
b-wave spectral sensitivity in the zebrafish that mapped
first-order cellular and biophysical aspects of cone photoreceptors
(visual pigment absorbance spectra and cone fractions) onto
a second-order physiological aspect of cone-derived neural activity
in the retina. Good correspondence between the model and photopic
ERG data was attained using new visual pigment absorbance data
for zebrafish cones (λmax of the L, M, and S
cones were 564, 473, and 407 nm, respectively), visual pigment
templates, and linearly gained cone fractions. The model inferred
four distinct cone processing channels that contribute to the
photopic b-wave, two of which are antagonistic
combinations of cone-derived signals (L-M and M-S), and two
of which are noncombinatorial signals from S and U cones. The
nature of the gains and the processing channels suggested general
rules of cone-specific inputs to second-order neurons. The model
further suggested that the zebrafish retina utilizes neuronal
mechanisms for enhancing sensitivity to luminance contrast at
short wavelengths and chromatic contrast at middle and long
wavelengths. The results indicated that first-order cellular
and biophysical aspects of cone photoreceptors can successfully
explain physiological aspects of cone-derived neuronal activity
in the zebrafish retina.
Transgenic expression of a GFP-rhodopsin COOH-terminal fusion
protein in zebrafish rod photoreceptors
Authors: PERKINS BRIAN D. , KAINZ PAMELA M. , O'MALLEY DONALD M. , DOWLING JOHN E.
Published: December 2002

(Article appeared in Visual Neuroscience (2002),
19, 257–264.)

Due to a production error, we are reprinting the following article
because the color images were printed in black and white. The color
images are so very important to the understanding of this article, we
are reprinting it here with the color images in place.
Does the neurotransmitter transporter underlie adaptation
at a histaminergic photoreceptor synapse?
Authors: STUART ANN E. , GEBHARDT KELLEY A. , VOGEL STACY N. , RODRIGUEZ OLGA
Published: December 2002

Using autoradiographic and biochemical techniques, we studied
the sodium-dependent forward and reverse transport of the
neurotransmitter histamine in an arthropod photoreceptor in
order to test whether the transporter plays a central role in
visual signal transfer at this synapse. In particular, we asked
whether the histamine transporter might be the important factor
in synaptic adaptation, the process by which the operating range
of the synapse adapts to increasing depolarizations of the
photoreceptor in increasing background light. Drugs known from
electrophysiological observations to interfere with synaptic
adaptation blocked the uptake of [3H]histamine into
photoreceptors. These drugs also blocked the sodium (Na)-triggered
efflux of [3H]histamine, previously loaded into
photoreceptors, via the histamine transporter. Several
lines of evidence showed that efflux of [3H]histamine
did not occur via calcium-dependent exocytosis. First,
efflux occurred when the preparation was bathed in calcium
(Ca)-free/EGTA salines or in cobalt (Co)-containing salines.
Even more importantly, efflux could be elicited from axons,
whose membranes must contain the transporter protein since they
take up [3H]histamine independently from the presynaptic
terminals. Since both adaptation and the histamine transporter
are blocked by the same agents, the transporter may underlie
adaptation by maintaining the cleft histamine concentration
in a particular range independent of light intensity. We also
characterized the transporter further and found that it is
partially dependent on chloride ions, and that neither
[3H]norepinephrine nor [3H]dopamine are
transported (at 20 μM), adding to evidence that the transporter
is highly selective for histamine.
cGMP modulates spike responses of retinal ganglion cells
via a cGMP-gated current
Authors: KAWAI FUSAO , STERLING PETER
Published: December 2002

Certain ganglion cells in the mammalian retina are known to
express a cGMP-gated cation channel. We found that a cGMP-gated
current modulates spike responses of the ganglion cells in mammalian
retinal slice preparation. In such cells under current clamp, bath
application of the membrane-permeant cGMP analog (8-bromo-cGMP,
8-p-chlorophenylthio-cGMP) or a nitric oxide donor (sodium
nitroprusside, S-nitroso-N-acetyl-penicillamine) depolarized the membrane
potential by 5–15 mV, and reduced the amount of current needed
to evoke action potentials. Similar effects were observed when the
membrane potential was simply depolarized by steady current. The
responses to cGMP are unaffected by inhibitors of cGMP-dependent protein
kinase and Ca2+/calmodulin-dependent protein kinase. The
response to cGMP persisted in Ca2+-free bath solution with
Ca2+ buffers in the pipette. Under voltage clamp, cGMP
analogs did not affect the response kinetics of voltage-gated
currents. We conclude that cGMP modulates ganglion cell spiking
simply by depolarizing the membrane potential via the
inward current through the cGMP-gated channel. Modulation of
this channel via the long-range NO-synthase amacrine
cell may contribute to control of contrast gain by peripheral
mechanisms.
Co-expression of murine opsins facilitates identifying the
site of cone adaptation
Authors: EKESTEN BJÖRN , GOURAS PETER , HARGITAI JANOS
Published: December 2002

Murine cones contain two opsins in the same cone, one ultraviolet
(UV) and the other middle-wavelength sensitive (M). A
long-wavelength flash only affecting M-opsin suppresses the
cone electroretinogram (ERG) produced by light absorption of
UV-cone opsin raising the hypothesis that activation of M-cone
opsin suppresses UV-cone opsin responses in the same cone. Here
we show that pharmacologic blockade of synaptic transmission
in the superfused murine retina, which eliminates interaction
from second-order neurons, fails to prevent suppression of the
UV-opsin driven pathway by long-wavelength stimuli. This proves
that the antagonism must be occurring in the same cone,
co-expressing both opsins. Our results show that UV-opsin
suppression successively ceases in presence of the M-opsin
activating background light, which implies that cone light
adaptation is controlled at the opsin stage, before activation
of transducin. It also reveals the time course of a transient
desensitization of cones due to post-opsin factors in the
transduction cascade.
Photoreceptor inner segments in monkey and human retina:
Mitochondrial density, optics, and regional variation
Authors: HOANG Q.V. , LINSENMEIER R.A. , CHUNG C.K. , CURCIO C.A.
Published: December 2002

The present work quantifies aspects of photoreceptor structure
related to mitochondria, inner segment dimensions, and optical
properties, as a basis for furthering our understanding of rod
and cone function. Electron-microscopic analyses were performed
on the retina of one stumptail macaque (Macaca arctoides)
to obtain stereological measurements of ellipsoid mitochondrial
density, and sizes and shapes of outer and inner segments. In
addition, the distribution of mitochondria and the optical
properties of human foveal cones were examined with electron
microscopy and Nomarski differential interference contrast (NDIC)
imaging. Mitochondria comprised 74–85% of cone ellipsoids
and 54–66% of rod ellipsoids in macaque. Ellipsoid volume
increased with eccentricity by 2.4-fold for rods and more than
6-fold for cones over eccentricities to 12.75 mm, while the
volume of the outer segment supported by the ellipsoid was
essentially constant for both rods and cones. Per unit volume
of outer segment, cones contained ten times as much mitochondria
as rods. In human fovea, as in the rest of the retina, most
cone mitochondria were located in the distal inner segment.
In the foveal center, however, there are also mitochondria in
the myoid, as well as in the outer fiber, proximal to the external
limiting membrane (ELM). Analyses of the optical aperture of
human foveal cones, the point at which their refractive index
clearly differs from the extrareceptoral space, showed that
it correlated well with the location of mitochondria, except
in the foveal center, where the aperture appeared proximal to
the ELM. While mitochondria have an important metabolic function,
we suggest that the striking differences between rods and cones
in mitochondrial content are unlikely to be determined by metabolic
demand alone. The numerous cone mitochondria may enhance the
waveguide properties of cones, particularly in the periphery.
Contrast adaptation: Paradoxical effects when the temporal
frequencies of adaptation and test differ
Authors: HEINRICH THOMAS STEPHAN , BACH MICHAEL
Published: December 2002

Previous studies of human contrast adaptation employing visually
evoked potentials (VEP) have revealed contradictory results,
namely, either a reduction or an enhancement in VEP amplitude.
In a cross-adaptation experiment, we explored the possibility
that differences in the temporal frequency of adapting and test
patterns played a role. Phase-reversing checkerboard stimuli
[1-deg check size, temporal frequency 8.5 or 17 reversals
per second (rps)] served as adaptation and test pattern
with contrasts of 0 or 97%. In 13 subjects, we recorded both
retinal (PERG) and cortical (VEP) steady-state responses
simultaneously. In a balanced block design, all four combinations
of the temporal adaptation and test frequencies were employed.
Contrast adaptation reduced the PERG amplitude by about 20%
in every temporal condition (P < 0.001). The VEP
amplitude was strongly affected by adaptation, but the effect
differed in magnitude and sign depending on condition: With
identical adaptation and test frequency, amplitude was reduced
by 15% (P = 0.07) at 8.5 rps and by 38% at 17 rps (P
< 0.05). Adapting at 8.5 rps and testing at 17 rps had a tiny (14%)
insignificant effect, whereas adapting at 17 rps and testing at 8.5 rps
revealed an amplitude enhancement of 27% (P < 0.05). These
strong temporal cross-adaptation effects (in the VEP, but not in the PERG)
suggest that the adaptable cortical mechanisms (gain control) can be narrowly
tuned in their temporal properties. A sizable adaptation effect can even
change its sign when varying the temporal frequency by a factor of two.
This finding resolves contradictions between previous VEP adaptation studies
and reconciles them with psychophysical findings.
Rabbit retinal ganglion cell responses mediated by
α-bungarotoxin-sensitive nicotinic acetylcholine receptors
Authors: REED B.T. , AMTHOR F.R. , KEYSER K.T.
Published: December 2002

The responses of many ganglion cells in the rabbit retina are
mediated, at least in part, by acetylcholine (ACh) acting on
neuronal nicotinic acetylcholine receptors (nAChRs). nAChRs
are comprised of α and β subunits; three β subunits
and nine α subunits of nAChRs have been identified and these
subunits can combine to form a large number of functionally
distinct nAChR subtypes. We examined the effects of cholinergic
agents on the light-evoked responses of ganglion cells to determine
which nAChR subtypes mediate the effects of ACh. Extracellular
recordings of retinal ganglion cells were made in intact everted
eyecup preparations and nicotinic agonists and antagonists were
added to the superfusate. While several ganglion cell classes
exhibited methyllycaconitine (MLA) sensitivity, the directionally
selective (DS) ganglion cells were most sensitive; exposure
to 30 nanomolar MLA, a concentration reportedly too low to affect
αBgt-insensitive nAChRs, suppressed the stimulus-evoked
responses of DS cells without eliminating directional selectivity.
Epibatidine, which at low concentrations is an agonist selective
for αBgt-insensitive nAChRs, stimulated firing of various
cell types including DS ganglion cells at low nanomolar
concentrations. The effects of the various agents tested persisted
under cobalt-induced synaptic blockade. The low nanomolar MLA
and epibatidine sensitivity of DS cells suggests that DS ganglion
cells express both αBgt-sensitive and αBgt-insensitive
nAChRs. Other ganglion cell types appear to express only
αBgt-sensitive nAChRs but not αBgt-insensitive nAChRs.
The spatial extent over which neurons in macaque striate
cortex pool visual signals
Authors: LEVITT JONATHAN B. , LUND JENNIFER S.
Published: December 2002

We recorded activity of single units in macaque monkey primary
visual cortex (V1) to define the retinotopic extent of the visual
inputs that drive or modulate V1 neuron responses in parafoveal
and peripheral (calcarine) cortex. We used high-contrast drifting
grating stimuli to define the extent of the area over which
responses summate and the extent of the receptive-field surround.
We found responses of most V1 cells to summate over 1 deg, with
a suppressive surround typically twice that in diameter, though
for some cells (even in parafoveal V1) surrounds exceeded 13
deg in diameter. Surprisingly, we found no significant laminar
differences in these dimensions or in the strength of surround
suppression. We found that surround suppression in most cells
arises from both the ends and sides of the receptive field.
Our measures indicate that the strongest modulatory input arises
from regions immediately adjacent to the excitatory summation
area. These physiological measures suggest that the high-contrast
summation field of V1 neurons can be accounted for by the sum
of lateral geniculate nucleus (LGN) inputs offered to the local
cortical column, with monosynaptic lateral connections within
area V1 adding the larger dimensions of the low-contrast summation
field and the near surround. Neither of these inputs suffice
to explain the largest surrounds, which most likely derive from
feedback from extrastriate visual areas.
Expression and distribution of ionotropic glutamate receptor
subunits on parasol ganglion cells in the primate retina
Authors: LIN BIN , MARTIN PAUL R. , GRÜNERT ULRIKE
Published: December 2002

The response properties of postreceptoral sensory neurones
are determined by the properties of their input neurones, by
intrinsic membrane properties, and by the properties of
neurotransmitter receptors on the soma and dendritic tree. We
previously showed that inhibitory neurotransmitter
(GABAA and glycine) receptors on a well-characterised
sensory neurone, the parasol ganglion cell in the primate retina,
are segregated towards the distal part of the dendritic tree.
Here we studied the distribution of excitatory ionotropic glutamate
receptor subunits on the dendrites of parasol cells in the retina
of a New World monkey, the marmoset, Callithrix jacchus.
Individual ganglion cells were intracellularly injected in an
in vitro retinal wholemount preparation. Ionotropic
glutamate receptor subunits, including AMPA (GluR1-4), kainate
(GluR6/7), NMDA (NR1C2′) subunits, and the orphan receptors
δ1 and δ2 were visualized with immunocytochemical methods.
Immunoreactive puncta that colocalized with the dendrites of
ganglion cells were analyzed using standard and/or confocal
light microscopy. Colocalized puncta were present on parasol
dendrites for all subunits studied, but their density was much
lower (approximately 1/5) than previously reported for inhibitory
(GABA and glycine) receptors. Segregation of the glutamate receptor
clusters (GluR1, GluR6/7 subunits) to the peripheral dendrites
was less marked than that shown for GABA and glycine receptor
clusters. No sign of segregation of colocalized puncta to the
peripheral part of the dendritic field was seen with antibodies
to the GluR2, GluR2/3, GluR4, δ1/2, or NR1C2′ subunits.
The results suggest that although there is diverse expression
of glutamate receptor subtypes, the glutamatergic synapses form
only a small proportion of the total synaptic input to primate
ganglion cells. They further suggest that the processes which
control distribution of excitatory and inhibitory synapses on
the dendritic field of ganglion cells are, at least to some
extent, independent.
Visual pigments and dichroism of anchovy cones: A model system
for polarization detection.
Authors: FLAMARIQUE IÑIGO NOVALES , HÁROSI FERENC I.
Published: December 2002

The retinas of anchovies have two unique photoreceptor types:
“bifid” and “long” cones (Fineran &
Nicol, 1976). The outer segments of these cells contain multiple
layers of membranes (lamellae) oriented longitudinally (axially).
This orientation is distinct from that in all other vertebrate
rods and cones, where the lamellae are stacked transversely
with their planes perpendicular to the incident light path.
Although the common arrangement provides optimal absorption
for normally incident light rays, it is also insensitive to
the rays' direction of vibration (i.e. their polarization).
In contrast, the two mutually perpendicular sets of axially
oriented lamellae segregated into bifid and long cones could
function as the principal analyzers for linearly polarized light,
as previously hypothesized (Fineran & Nicol, 1976, 1978).
Here, we report on a microspectrophotometric study that shows
(1) the presence of two spectrally distinct visual pigments
in the three photoreceptor types of the bay anchovy retina;
these are typical vertebrate pigments in that they bleach, when
exposed to light, and have absorption spectra like all other
vitamin A1-based visual pigments; (2) that the rods
and cones exhibit dichroic absorption of light in accordance
with their lamellar orientation, and (3) that the two cone types
of the retina contain a spectrally indistinguishable pigment
with peak absorbance (λmax) around 540 nm, while
the rods contain a rhodopsin-like pigment with λmax
near 500 nm. Compared to other vertebrates, anchovies are
remarkable for using a monochromatic cone system with unusual
specializations supportive of a polarization detection system.
Fixational ocular motor control is plastic despite visual
deprivation
Authors: HALL E.C. , CIUFFREDA K.J.
Published: December 2002

The aim of this study was to assess the plasticity of human
voluntary fixational eye movement control in relation to visual
experience/chronic visual deprivation. Twelve blind adults
participated (self-reported vision ≤ light perception in
each eye; age range = 23–56 years; visual experience range
= 0–28 years; blindness duration range = 6–55 years).
Infrared-based recordings of horizontal eye movements were made
before, during, and immediately after three 30-s periods of
auditory ocular motor feedback, while participants were instructed
to look straight ahead and keep their eyes as steady as possible.
Percent change in horizontal displacement of the eye during
and after feedback was compared with the no-feedback baseline.
Eleven of the 12 individuals demonstrated feedback-mediated increase
in eye stability, which improved as a function of visual experience.
Improved eye stability was inversely related to duration of blindness.
Clearly, blind adults can use nonvisual external feedback to
stabilize gaze. Thus, the fixational subsystem can exhibit improved
voluntary control despite chronic visual deprivation. Possible
cortical and subcortical mechanisms are discussed.
Large-scale morophological survey of rat retinal ganglion cells
Authors: SUN WENZHI , LI NING , HE SHIGANG
Published: December 2002

Ganglion cells in an isolated wholemount preparation of the
rat retina were labeled using the “DiOlistic” labeling
method (Gan et al., 2000) and were classified according to their
morphological properties. Tungsten particles coated with a
lipophilic dye (DiI) were propelled into the wholemount retina
using a gene gun. When a dye-coated particle contacted the cell
membrane, the entire cell was labeled. The ganglion cells were
classified into four types based on their soma size,
dendritic-field size, branching pattern, and level of
stratification. Broadly monostratified cells were classified
into three types: RGA cells (large soma, large dendritic
field); RGB cells (small- to medium-sized soma, small-
to medium-sized dendritic field); and RGC cells (small-
to medium-sized soma, medium-to-large dendritic field).
Bistratified cells were classified as RGD. Several
subtypes were identified within each ganglion cell group. A
number of new subtypes were discovered and added into the existing
catalog, among them were two types of bistratified cells. This
study therefore represents the most complete morphological
classification of rat retinal ganglion cells available to date.
Effects of the destruction of starburst-cholinergic amacrine
cells by the toxin AF64A on rabbit retinal directional selectivity
Authors: AMTHOR FRANKLIN R. , KEYSER KENT T. , DMITRIEVA NINA A.
Published: December 2002

The effects of intraocular injections of ethylcholine mustard
aziridinium ion (AF64A), an irreversible inhibitor of choline
uptake, on the rabbit retina were assessed electrophysiologically,
pharmacologically, anatomically, and behaviorally. Survival
times from 1 day to 30 days were investigated. After 24 h, the
shortest time tested, the directional selectivity of On–Off
responding ganglion cells having the characteristic morphology
of On–Off directionally selective directionally selective
(DS) ganglion cells, as revealed by intracellular dye injection,
was significantly reduced, both by an apparent decrease of
preferred direction responses and an increase in responses to
null-direction movement. No toxin-mediated changes in the dendritic
trees of these cells were noted. Cells in AF64A-affected retinas
having the DS morphology did not respond significantly to GABAergic
or cholinergic agents such as picrotoxin and eserine, but did
respond to nicotine. Recordings from a small random sample of
other ganglion cell classes in the same retinas yielded no obvious
changes in response properties. The direct effects on starburst
(cholinergic) amacrine cells, which were identified by intraocular
injection of the fluorescent dye DAPI with the AF64A, were
investigated by intracellular injections of Lucifer yellow,
and by immunohistochemical staining with antibodies to choline
acetyltransferase (ChAT). Although starburst amacrine cell somas
survived the AF64A treatment for at least several days, the
dendrites could not be visualized by fluorescent dye injection
in affected retinas due to dye leakage of the injected fluorescent
dye from either the soma or proximal dendritic region. ChAT
staining revealed a sequence in which ChAT-positive cells were
undetectable first in the inner nuclear layer, and then in the
ganglion cell layer. Cholinergic amacrine cells in the central
retina were also affected before those in the periphery. The
electrophysiological changes observed typically preceded the
loss of ChAT activity. Behavioral tests for optokinetic nystagmus
responses also revealed a lack of such responses in the affected
eyes.
Organization of reciprocal connections between the
perigeniculate nucleus and dorsal lateral geniculate nucleus
in the cat: A transneuronal transport study
Authors: FITZGIBBON T.
Published: December 2002

Cells of the cat's perigeniculate nucleus (PGN), part
of the visual sector of the thalamic reticular nucleus (TRN),
provide GABAergic inhibition to the A and A1 layers of the dorsal
lateral geniculate nucleus (LGNd) and, therefore, may control
information flow from the retina to the cortex. Previous
electrophysiological experiments suggested that the PGN may
be subdivided on the basis of ocular dominance thus reflecting
the afferent and efferent projections with lamina A and A1 of
the LGNd. The present study utilized the ability of wheat germ
agglutinin-horseradish peroxidase (WGA-HRP) to be transported
transneuronally following intraocular injections in four cats
to examine whether there is any anatomical evidence for eye
specific layers within the PGN. Sections were processed with
tetramethylbenzidine. Light WGA-HRP transneuronal labeling of
LGNd collaterals and somata were seen in the PGN and very light
labeling (but not somata) was seen in the TRN. Neither the cells
of the PGN projecting to the LGNd nor the LGNd relay collaterals
within the PGN were clearly organized into nonoverlapping laminae
related to the eye specific layers of the LGNd. However, parts
of the PGN immediately adjacent to the LGNd appear devoid of
connections with lamina A1 thus creating a thin monocular segment
for the contralateral eye.
An albino-like decussation error in the optic chiasm revealed
by anomalous ocular dominance columns
Authors: SINCICH LAWRENCE C. , HORTON JONATHAN C.
Published: December 2002

We report a unique anomaly in the ocular dominance column pattern
of a single, normally pigmented macaque monkey. The column pattern
contained large monocular areas inserted between the normal
columns and the dorsal V1 border. These monocular regions received
transneuronal input from the contralateral eye, indicating that
a small population of temporal ganglion cells erroneously
decussated at the optic chiasm. Projection of the column pattern
back onto the visual field showed that the monocular wedges
represented a ∼5-deg sector of ipsilateral field. This
corresponded to the extent of naso-temporal overlap of ganglion
cells in the normal retina, suggesting an error in axon guidance
affecting cells close to the vertical midline of the retina.
The consequences of the crossing error in this animal were
threefold: it produced an anomalous monocular zone near the
V1 border, the vertical meridian was not represented at the
V1 border, and points near the vertical meridian were represented
twice in the brain, once in each hemisphere.