bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal adaptation through corticothalamic loops:
A hypothesis
Authors: HILLENBRAND ULRICH , van HEMMEN J. LEO
Published: July 2002

The thalamus is the major gate to the cortex and its
control over cortical responses is well established.
Cortical feedback to the thalamus is, in turn, the anatomically
dominant input to relay cells, yet its influence on thalamic
processing has been difficult to interpret. For an understanding
of complex sensory processing, detailed concepts of the
corticothalamic interplay need yet to be established. Drawing
on various physiological and anatomical data, we elaborate
the novel hypothesis that the visual cortex controls the
spatiotemporal structure of cortical receptive fields via
feedback to the lateral geniculate nucleus. Furthermore,
we present and analyze a model of corticogeniculate loops
that implements this control, and exhibit its ability of
object segmentation by statistical motion analysis in the
visual field.
Inhibition is not required for the production of transient
spiking responses from retinal ganglion cells
Authors: BIEDA MARK C. , COPENHAGEN DAVID R.
Published: July 2002

Ganglion cells responding only transiently to changes
in illumination are found in many different vertebrate
retinas. The interactions underlying formation of these
transient responses are still poorly understood. Two recently
proposed hypotheses are (1) functional inhibitory pathways
are necessary for transient response production, and (2)
direct inhibition of the ganglion cell has little effect
on its output. Here, we examine these conclusions by using
cell-attached patch-clamp recordings of spiking, whole-cell
recordings of synaptic currents, and computer modeling.
We found that picrotoxin (a GABAA and GABAC
receptor antagonist), bicuculline (a GABAA receptor
antagonist), and strychnine (a glycine receptor antagonist),
applied either singly or in combination, always failed
to convert transient responses to sustained responses.
Application of the GABAB antagonist CGP35348
in the presence of picrotoxin and strychnine also failed
to convert transient responses into sustained responses.
Whole-cell recordings of synaptic currents at various holding
potentials indicated that direct inhibitory inputs to ganglion
cells limit the duration of net excitation, implying that
direct inhibition does act to truncate the ganglion cell
spiking response. Computer simulations using spiking and
synaptic data from combined cell-attached and whole-cell
recordings supported this interpretation. We conclude that
inhibitory pathways are not required for generation of
transient responses, but these pathways do serve to modulate
transient ganglion cell spiking responses. We find that
this modulation occurs, in part, via inhibitory
inputs directly to the ganglion cell.
Dye coupling in horizontal cells of developing rabbit retina
Authors: JOHNSON DIANNA A. , MILLS STEPHEN L. , HABERECHT MICHAEL F. , MASSEY STEPHEN C.
Published: July 2002

In the mature rabbit retina, two classes of horizontal
cells, A type and B type, provide lateral inhibition in
the outer plexiform layer (OPL) and spatially modify the
activation of bipolar cells by photoreceptors. Gap junctions
connecting homologous horizontal cells determine the extent
to which this inhibitory activity spreads laterally across
the OPL. Little is currently known about the expression
of gap junctions in horizontal cells during postnatal development
or how cell–cell coupling might contribute to subsequent
maturational events. We have examined the morphological
attributes and coupling properties of developing A and
B type horizontal cells in neonatal rabbit retina using
intracellular injections of Lucifer Yellow and Neurobiotin.
Prelabeling with DAPI permitted the targeting of horizontal
cell bodies for intracellular injection in perfused preparations
of isolated retina. A and B type horizontal cells were
identifiable at birth although their dendritic field sizes
had not reached adult proportions and their synaptic contacts
in the OPL were minimal. Both cell types exhibited homologous
dye coupling at birth. Similar to that seen in the adult,
no heterologous coupling was observed, and homologous coupling
among A type cells was stronger than that observed among
B type cells. The spread of tracer compounds through gap
junctions of morphologically immature horizontal cells
suggests that ions and other small, bioactive compounds
may likewise spread through coupled, horizontal networks
to coordinate the subsequent maturational of emerging outer
plexiform layer pathways.
The functional influence of nicotinic cholinergic receptors on the
visual responses of neurones in the superficial superior colliculus
Authors: BINNS K.E. , SALT T.E.
Published: July 2002

In the rat, the superficial gray layer (SGS) of
the superior colliculus receives glutamatergic projections
from the contralateral retina and from the visual cortex.
A few fibers from the ipsilateral retina also directly
innervate the SGS, but most of the ipsilateral visual input
is provided by cholinergic afferents from the opposing
parabigeminal nucleus (PBG). Thus, visual input carried
by cholinergic afferents may have a functional influence
on the responses of SGS neurones. When single neuronal
extracellular recording and iontophoretic drug application
were employed to examine this possibility, cholinergic
agonists were found to depress responses to visual stimulation.
Lobeline and 1-acetyl-4-methylpiperazine both depressed
visually evoked activity and had a tendency to reduce the
background firing rate of the neurones. Carbachol depressed
the visual responses without any significant effect on
the ongoing activity, while the muscarinic receptor selective
agonist methacholine increased the background activity
of the neurones and reduced their visual responses. Lobeline
was chosen for further studies on the role of nicotinic
receptors in SGS. Given that nicotinic receptors are associated
with retinal terminals in SGS, and that the activation
of presynaptic nicotinic receptors normally facilitates
transmitter release (in this case glutamate release), the
depressant effects of nicotinic agonists are intriguing.
However, many retinal afferents contact inhibitory neurones
in SGS; thus it is possible that the increase in glutamate
release in turn facilitates the liberation of GABA which
goes on to inhibit the visual responses. We therefore attempted
to reverse the effects of lobeline with GABA receptor antagonists.
The depressant effects of lobeline on the visual response
could not be reversed by the GABAA antagonist
bicuculline, but the GABAB antagonist CGP 35348
reduced the effects of lobeline. We hypothesize that cholinergic
drive from the parabigeminal nucleus may activate presynaptic
nicotinic receptors on retinal terminals, thereby facilitating
the release of glutamate onto inhibitory neurones. Consequently
GABA is released, activating GABAB receptors,
and thus the ultimate effect of nicotinic receptor activation
is to depress visual responses.
Cloning and tissue localization of a novel zebrafish RdgB
homolog that lacks a phospholipid transfer domain
Authors: ELAGIN VECHESLAV A. , ELAGINA RAYA B. , DORO CHRISTOPHER J. , VIHTELIC THOMAS S. , HYDE DAVID R.
Published: July 2002

The retinal degeneration B (RdgB) protein family
is characterized by an amino-terminal phosphatidylinositol
transfer protein (PITP) domain, several hydrophobic domains,
and a highly conserved carboxyl terminus. We identified
a zebrafish RdgB homolog (pl-RdgB) that lacks the amino-terminal
PITP domain, while retaining over 45% amino acid identity
with the two mouse RdgB proteins (M-RdgB1 and M-RdgB2).
Unlike the widespread retinal expression observed for other
vertebrate RdgB homologs, pl-RdgB is restricted in the
retina to the cone cell inner segments. The pl-RdgB protein
is also expressed in the brain, although its distribution
is different than the other RdgB homologs. Analogous to
M-RdgB2, pl-RdgB protein is extracted from a retinal homogenate
by guanidine and not by Triton X-100. Thus, pl-RdgB and
likely all the identified RdgB homologs are not integral
membrane proteins, but may associate with the membrane
through protein–protein interactions. While expression
of either murine RdgB homolog restored the defective light
response and prevented retinal degeneration in rdgB
mutant flies, expressing zebrafish pl-RdgB in Drosophila
rdgB2 null mutants slowed retinal degeneration
without restoring the electrophysiological light response.
Thus, pl-RdgB may define a previously unrecognized protein
family, which includes the other RdgB homologs, that act
through a protein complex to maintain photoreceptor viability.
Suppression outside the classical cortical receptive field
Authors: WALKER GARY A. , OHZAWA IZUMI , FREEMAN RALPH D.
Published: July 2002

The important visual stimulus parameters for a
given cell are defined by the classical receptive field
(CRF). However, cells are also influenced by visual stimuli
presented in areas surrounding the CRF. The experiments
described here were conducted to determine the incidence
and nature of CRF surround influences in the primary visual
cortex. From extracellular recordings in the cat's
striate cortex, we find that for over half of the cells
investigated (56%, 153/271), the effect of stimulation
in the surround of the CRF is to suppress the neuron's
activity by at least 10% compared to the response to a
grating presented within the CRF alone. For the remainder
of the cells, the interactions were minimal and a few were
of a facilitatory nature. In this paper, we focus on the
suppressive interactions. Simple and complex cell types
exhibit equal incidences of surround suppression. Suppression
is observed for cells in all layers, and its degree is
strongly correlated between the two eyes for binocular
neurons. These results show that surround suppression is
a prevalent form of inhibition and may play an important
role in visual processing.
GABA responses of rod bipolar cells in rabbit retinal slices
Authors: McGILLEM GREGORY S. , ROTOLO THOMAS C. , DACHEUX RAMON F.
Published: July 2002

GABAergic responses of rabbit rod bipolar cells were
reexamined by using whole-cell recordings in the superfused
slice preparation to determine if there is GABAC
receptor input to their axon terminal and to characterize
the contribution that GABAA and GABAC
receptors make to the total GABA current on the axon terminals
of these cells. Pharmacological agents specifically blocking
GABAA and GABAC receptor currents
demonstrated that 37% of the GABA-activated current was
blocked by either the GABAA antagonists bicuculline
or SR-95531, whereas the remaining 63% of the GABA current
was blocked by a mixture of bicuculline and the GABAC
antagonist TPMPA. This indicated that GABAC
receptors were present on the axon terminal of the rabbit
rod bipolar cell and that they were responsible for mediating
the bicuculline insensitive GABA current.
Distribution of the α1 subunit of the GABAA
receptor on midget and parasol ganglion cells in the retina
of the common marmoset Callithrix jacchus
Authors: MACRI JOSEPH , MARTIN PAUL R. , GRÜNERT ULRIKE
Published: July 2002

The inhibitory neurotransmitter gamma aminobutyric acid
(GABA) has been shown to influence the responses of ganglion
cells in the mammalian retina. Consistently, GABAA
receptor subunits have been localized to different ganglion
cell types. In this study, the distribution of the α1
subunit of the GABAA receptor on the dendrites
of midget and parasol ganglion cells was investigated quantitatively
in the retina of a New World monkey, the marmoset. Ganglion
cells were injected with Neurobiotin in a live in vitro
retinal whole-mount preparation. Retinal pieces were then
processed with an antibody against the α1 subunit of
the GABAA receptor. Strong punctate immunoreactivity
indicative of synaptic localization is present in the ON
and OFF sublamina of the inner plexiform layer. Many of
the immunoreactive puncta coincide with the dendrites of
both midget and parasol ganglion cells. Immunoreactive
puncta are present on distal and proximal dendrites of
ON and OFF cells of both ganglion cell types. On average,
parasol cells show a slight increase in the spatial density
of immunoreactive puncta with distance from the soma, whereas
the density of immunoreactive puncta on midget cells stays
even. Parasol ganglion cells show a slightly higher average
density of immunoreactive puncta (0.083 puncta/μm dendrite)
than midget cells (0.054 puncta/μm dendrite).
Second messenger pathways involved in up-regulation of an
L-type calcium channel
Authors: LINN CINDY L.
Published: July 2002

Catfish cone horizontal cells contain a voltage-gated
L-type calcium channel that is modulated by activation
of metabotropic glutamate receptors (mGluRs). Activation
of group I mGluRs with the mGluR I agonist, (S)-3,5-dihydroxyphenylglycine
[(S) 3,5-DHPG], potentiated peak calcium current
amplitude, shifted the membrane potential corresponding
to peak current activity, and widened the calcium current's
activation range. In this study, we have examined the mechanisms
linking activation of the mGluRs with “up-regulation”
of calcium current activity. Under whole-cell voltage-clamp
conditions favoring expression of the L-type calcium current,
we provide evidence that activation of mGluRs initiate
the diacylglyceral (DG) second messenger pathway to activate
protein kinase C (PKC) and up-regulate calcium channel
activity. This evidence was based on results using a number
of PKC activators and inhibitors. PKC activators mimicked
the effect of (S) 3,5-DHPG on calcium current activity.
Up-regulation of the calcium channel by PKC activators
or (S) 3,5-DHPG was eliminated if PKC inhibitors were present.
These results also demonstrated that activation of group
I mGluRs were linked to a pertussis toxin sensitive G-protein.
When the GTP analog, guanosine 5-0-(3-thiotriphosphate
(GTPγS), was allowed to diffuse into voltage-clamp
cells, up-regulation of the calcium channel occurred and
mimicked the effect of (S) 3,5-DHPG. However, when pertussis
toxin (PTX) was allowed to diffuse into the cell along
with GTPγS, GTPγS failed to modulate calcium current
activity. IP3 (inositol 1,4,5 triphosphate)
is a second product produced by activation of group I mGluRs.
Once formed, IP3 can trigger calcium release
from IP3-sensitive intracellular stores. To
determine if the IP3 second messenger system
was involved in up-regulation of calcium channel, (S) 3,5-DHPG
was applied to voltage-clamped cone horizontal cells containing
different concentrations of the calcium buffer, EGTA. Low
concentrations of EGTA failed to buffer calcium released
from intracellular stores. In the presence of low EGTA
concentrations, (S) 3,5-DHPG's enhancement of the
calcium current amplitude was reduced. Inhibition of the
calcium current amplitude in low concentrations of EGTA
was eliminated in the presence of the intracellular calcium
store blocker, heparin. These results suggest that both
the DG and IP3 second messenger pathways are
involved in modulation of the voltage-gated calcium channel
in catfish cone horizontal cells. The DG pathway up-regulates
the voltage-gated calcium channel activity whereas calcium
released from IP3 intracellular stores inhibits
peak current amplitude.
Noise and light adaptation in rods of the macaque monkey
Authors: SCHNEEWEIS D.M. , SCHNAPF J.L.
Published: July 2002

Membrane voltage was recorded in rod photoreceptors in
retina isolated from macaque monkey. The size of the single
photon response and the magnitude of membrane voltage fluctuations
were assessed in dark- and light-adapted retina. The “dark
light” rate ID, defined as the
rate of spontaneous photopigment isomerizations that would produce
a variance equivalent to that of the noise measured in the dark, was
calculated after matched filtering. The average value of 0.08
s−1 fell at the higher end of psychophysical
estimates of dark light in human observers. In light-adapted rods
the photon response decreased in amplitude and duration, and the
magnitude of the voltage fluctuations increased with increasing
background light intensity. The signal-to-noise ratio (SNR) for single
rods was defined as the ratio of the peak amplitude of the photon response
to the standard deviation of the noise fluctuations. The signal-to-noise
ratio for dark-adapted rods SNRD was about 7. With increasing
background intensity I, the SNR fell as SNRD(1 +
I/ID)−1/2.
This function may account for the increment thresholds measured with
small brief test flashes in human psychophysical experiments.
Effects of nitric oxide on horizontal cells in the rabbit retina
Authors: XIN DAIYAN , BLOOMFIELD STEWART A.
Published: July 2002

Retinal horizontal cells display large receptive fields
as a result of extensive electrical coupling via
gap junctions. There is abundant evidence that these gap
junctions are dynamically regulated by changes in the adaptational
state of the retina. The neuromodulator dopamine appears
to play a major role in regulating gap junctional conductances
of horizontal cells. Emerging evidence indicates that nitric
oxide (NO) also acts as a neuromodulator in the retina
and, more specifically, regulates the coupling between
horizontal cells. In the present study, we examined the
effects of a nitric oxide, and its secondary messenger
cGMP, on electrical and tracer coupling between A-type
and between B-type horizontal cells in the rabbit retina.
Application of the NO donors S-nitroso-N-acetylpenicillamine
(SNAP) or sodium nitroprusside (SNP) significantly reduced
the coupling between horizontal cells as evidenced by a
decrease in their space constants, annulus-to-small spot
response ratios, and the extent of tracer coupling following
injection with Neurobiotin. Further, application of SNP
eliminated the increase in coupling of horizontal cells
normally seen with exposure to dim background illumination.
Application of 8-bromo-cGMP produced effects similar to
those of the NO donors, consistent with the idea that the
uncoupling actions of NO were mediated via a cGMP
cascade.
Inhibitory control of synaptic activity in goldfish Mb bipolar
cell terminals visualized by FM1-43
Authors: MACK ANDREAS F. , BEHRENS UWE D. , WAGNER HANS-JOACHIM
Published: July 2002

To investigate the physiology and plasticity of mixed
rod–cone ON-bipolar cells (Mb) in the goldfish retina,
we established a slice preparation which allows us to optically
monitor the synaptic activity of bipolar cell axon terminals.
We used the styryl dye FM1-43 which is incorporated into
active axon terminals due to synaptic vesicle cycling and
thus reflects synaptic activity. Different activity states
of the axon terminals were revealed when slices prepared
from light-adapted retinae were incubated in the presence
of FM1-43 under various conditions. Depolarizing high K+
Ringer (50 mM) and the gamma-butyric acid (GABA) antagonist
bicuculline (100 μM) resulted in more than two-fold
increase in the number of stained terminals compared to
slices stained in normal Ringer. In contrast, GABA treatment
(0.5 mM) reduced the frequency of stained terminals. Thus,
in light-adapted retinal slices the synaptic activity of
Mb axon terminals can be modulated towards higher and lower
activity states. The fact that the GABA antagonist bicuculline
had similar effects as stimulatory high K+ Ringer
suggests that inhibitory control is an important component
in the regulation of synaptic activity and transmitter
release in Mb terminals.
Functional dopamine deficits in the senile rat retina
Authors: HANKINS M.W.
Published: July 2002

The activity of the endogenous retinal dopamine (DA)
pathway has been examined in the pigmented rat using retinas
obtained from normal adult (∼3 months) and senile adults
(∼24 months) using an in vitro electrophysiological
approach. By comparing the pharmacological sensitivity
of the horizontal cells (HCs) to exogenous DA, a D1 receptor
antagonist (SCH 23390) and a DA-transport inhibitor (nomifensine),
it is suggested that there is a functional deficit in the
endogenous DA activity in the senile retina. Cells recorded
from retinae obtained from senile animals are more sensitive
to exogenous DA, whilst the senile retina is insensitive
to SCH 23390. In addition, nomifensine was effective in
potentiating subthreshold DA applications, but only in
the normal adult retina. The data may suggest that endogenous
DA release upon the HCs and selective re-uptake are suppressed
in these retinae. These functional deficits also appear
to be associated with changes in the receptive fields of
the HCs, suggesting there is a corresponding deficit in
spatial processing at the outer plexiform layer (OPL) of
the senile rat.
The timecourse of neuronal connections of the rotundoectostriatal
pathway in chicks (Gallus gallus) during embryogenesis:
A retrograde transport study
Authors: WU CHI-CHENG , CHARLTON ROBERT K. , KARTEN HARVEY J.
Published: July 2002

The avian retinotectofugal pathway has been suggested
to be homologous to the mammalian retinotectofugal pathway.
The projection of the nucleus rotundus upon the ectostriatum
is equivalent to that of the pulvinar nucleus upon the
extrastriate cortex in mammals. In this system, the optic
tectum relays retinal input to the nucleus rotundus, which
then ascends to the ectostriatum of the telencephalon.
Given the fact that the chick retinotectofugal system becomes
mature early during development, the present study attempted
to investigate the timecourse of neuronal connections of
the embryonic rotundoectostriatal pathway. We used multiple
injections of cholera toxin B subunit (CTb) in the ectostriatum
of chick embryos to retrogradely trace projections to the
nucleus rotundus. We found CTb-labeled neurons in the nucleus
rotundus at embryonic day 7.5–8. By embryonic day
8–8.5, increased numbers of CTb-labeled neurons were
seen in the nucleus rotundus. It was noted that the time
of this initial connection between the nucleus rotundus
and the ectostriatum is nearly synchronous with that of
the retinotectal and tectorotundal pathways, respectively
(Crossland et al., 1975; Thanos & Bonhoeffer, 1987;
Wu et al., 2000). These findings, combined with the present
study, suggest that the retinotectofugal system becomes
established, at least at a structural level, by embryonic
day E8.
Temporal-chromatic interactions in LGN P-cells
Authors: LANKHEET MARTIN J.M. , LENNIE PETER , KRAUSKOPF JOHN
Published: July 2002

We studied the interaction between the chromatic
and temporal properties of parvocellular (P) neurons in
the lateral geniculate nucleus (LGN) of macaque monkeys.
We measured the amplitudes and phases of responses to stimulation
by spatially uniform fields modulated sinusoidally about
a white point in a three-dimensional color space, at a
range of temporal frequencies between 1 and 25 Hz. Below
about 4 Hz, temporal frequency had relatively little effect
on chromatic tuning. At higher frequencies chromatic opponency
was weakened in almost all cells. The complex interactions
between temporal and chromatic properties are represented
by a linear filter model that describes response amplitude
and phase as a function of temporal frequency and direction
in color space along which stimuli are modulated. The model
stipulates the cone inputs to center and surround, their
temporal properties, and the linear combination of center
and surround signals. It predicts the amplitudes and phases
of responses of P-cells, and the change of chromatic properties
with temporal frequency. We used the model to investigate
whether or not the chromatic signature of the surround
in a red–green cell could be estimated from the change
in the cell's chromatic properties with temporal frequency.
Our findings could be equally well described by mixed cone
surrounds as by pure cone surrounds, and we conclude that,
with regard to temporal properties, there is no benefit
to be gained by segregating cone classes in center and
surround.
Rescue of excitation by inositol following Li+-induced
block in Limulus ventral photoreceptors
Authors: JOHNSON EDWIN C. , GRAY-KELLER MARK P. , O'DAY PETER M.
Published: July 2002

The phosphoinositide (PI) intracellular signaling
pathway, which triggers Ca2+ release from intracellular
stores, appears to be a central feature of phototransduction
in most invertebrate species studied. Procedures designed
to inhibit PI-pathway reactions cause suppression of excitation
to dim lights. However, in Limulus photoreceptors,
responses to bright stimuli are in fact enhanced by some
of these procedures, suggesting that PI metabolism is not
obligatory for light-induced excitation. Other studies,
however, suggest that Ca2+ release is obligatory
for excitation. We studied this issue by examining the
effects of PI-pathway inhibitor, Li+, on electrophysiological
responses to light in Limulus photoreceptors.
Li+ is reported to cause depletion of intracellular
PI-pathway intermediate, inositol; and it offers the pharmacological
advantage that its block can be bypassed by introducing
exogenous inositol. Introduction of Li+ caused
a very slowly developing but complete suppression of responses
to dim stimuli. In contrast, Li+ caused a rapidly
developing but partial suppression of responses to bright
stimuli. Li+-induced suppression was reversed
by exogenous introduction of inositol. In addition, inositol
prevented Li+-induced suppression of excitation.
Li+ enhanced light adaptation (light-induced
desensitization) but slowed response deactivation, indicating
a difference in the processes underlying these phenomena.
Li+ slowed dark adaptation, the recovery of
sensitivity following light adaptation. All of these effects
were prevented or rescued by extracellularly applied inositol,
suggesting the presence of a transmembrane inositol transport
system. The overall results suggest that PI-dependent signaling
is central and obligatory for excitation in Limulus,
at least for responses to dim to moderate illumination.
The failure of Li+ to suppress bright light-induced
excitation completely may be due to a failure of Li+
to block PI metabolism completely, as in other systems;
however, it may point to a parallel, PI-independent excitation
pathway possessing very low light sensitivity when PI metabolism
is inhibited.
Receptive fields of primate retinal ganglion cells studied
with a novel technique
Authors: LEE BARRY B. , KREMERS JAN , YEH TSAIYAO
Published: July 2002

We have reinvestigated receptive-field structure
of ganglion cells of the macaque parafovea using counterphase
modulation of a bipartite field. Receptive fields were
mapped with luminance, chromatic, and cone-isolating stimuli.
Center sizes of middle (M) and long (L) wavelength cone
opponent cells of the parvocellular (PC) pathway were consistent
with previous estimates (Gaussian radii of 2–4 min
of arc, corresponding to center diameters of 6–12
min of arc). We calculate that a large factor of the enlargement
relative to cone radius could be blur due to the eye's
natural optics. Maps were consistent with cone selectivity
in surround mechanisms, which had radii of 5–8 min
of arc. For magnocellular (MC) cells, center size estimates
were also consistent with grating measurements from the
literature (also Gaussian radii of 2–4 min of arc).
The surround mechanism contributing the MC-cell frequency-doubled
response to chromatic modulation appears to possess a subunit
structure, and we speculate it derives from nonlinear summation
of signals from M,L-cone opponent subunits, such as midget
bipolar cells.
Effects of bicarbonate versus HEPES buffering on
measured properties of neurons in the salamander retina
Authors: HARE WILLIAM A. , OWEN W. GEOFFREY
Published: July 2002

Electrophysiological studies of the isolated retina
involve perfusing the tissue with a physiological Ringer's.
Organic pH buffers such as HEPES have become increasingly
popular in recent years because for many purposes they
offer a convenient and reliable alternative to the more
traditional bicarbonate/CO2. In this paper,
however, we report that important functional properties
of rods, bipolar cells, and horizontal cells in the salamander,
Ambystoma tigrinum, are sensitive to the choice
of buffer and, in the case of horizontal cells, that sensitivity
is acute. In bicarbonate/CO2 Ringer's,
the dark potential of the horizontal cell was typically
near −50 mV and saturating light caused it to hyperpolarize
to about −75 mV. On switching to HEPES-buffered Ringer's
at the same pH, horizontal cells depolarized in darkness
to about −20 mV, close to the chloride equilibrium
potential, and the kinetics of their light responses changed.
The cone-driven components of light responses increased
in size relative to rod-driven components. Saturating lights
still hyperpolarized the cells to −75 mV, however.
Horizontal cells, being coupled via gap junctions,
form a syncytium and syncytial length constants, measured
in bicarbonate/CO2 Ringer's, were generally
in the range 150–225 μm. On switching to HEPES-buffered
Ringer's, length constants increased substantially
to 250–330 μm. All these changes were reversible.
We discuss our findings within the context of the cell's
ability to regulate its internal pH.
Localization of gephyrin and glycine receptor subunit immunoreactivity
in the rabbit retina
Authors: ZUCKER CHARLES L.
Published: July 2002

Being utilized by over 40% of the amacrine cells,
glycine is considered to be a major inhibitory neurotransmitter
in the retinas of all vertebrate species examined. Localization
of gephyrin, which is a 93-kD peripheral membrane glycine
receptor-associated anchoring protein, has been used in
several studies to identify the sites of glycinergic interactions
in the retina and other regions of the central nervous
system. Recent studies have shown that gephyrin colocalizes
with GABAA receptors which, like those for glycine,
are also inhibitory amino acid receptors usually associated
with a chloride channel. In the present study, we have
used two antibodies which recognize either gephyrin (mAb7a),
or the α and β subunits of the glycine receptor
(mAb4a) in order to determine to what extent gephyrin is
associated with glycine receptors in the mammalian retina.
Single-label studies showed extensive punctate staining
throughout most of the inner plexiform layer with each
antibody. Double labeling showed that nearly 90% of the
glycine receptor sites were also immunoreactive for gephyrin.
However, nearly 60% of the total punctae immunoreactive
for gephyrin were not stained for glycine receptors. This
distinction was most pronounced in the most proximal inner
plexiform layer where only 24% of the gephyrin-immunoreactive
sites were glycine receptor positive. This study suggests
that although most glycine receptors in the rabbit retina
colocalize with the anchoring protein gephyrin, a significant
proportion of the gephyrin-labeled sites are not associated
with glycine receptors. In light of studies showing gephyrin
association with GABAA receptor subunits, the
localization of gephyrin may be indicative of chloride-mediated
inhibitory amino acid transmission in general and not solely
that of glycinergic. Given several studies which show that
bipolar cells express glycine receptors and respond to
glycine but do not express gephyrin, the 10% of glycine
receptors not colocalized with gephyrin shown in the present
study may represent a subtype of glycine receptors found
on bipolar cells which do not require gephyrin for the
functional clustering of receptor subunits.
Comparison of the distribution and somatodendritic morphology
of tectotectal neurons in the cat and monkey
Authors: OLIVIER ETIENNE , PORTER JOHN D. , MAY PAUL J.
Published: July 2002

The presence of a commissure connecting the two
superior colliculi suggests they do not act independently,
but the function of the tectotectal connection has never
been firmly identified. To develop a better understanding
of this commissural system, the present study determined
the distribution and morphology of tectotectal neurons
in the cat and macaque monkey, two animals with well-studied,
but different orienting strategies. First, we compared
the distribution of tectotectal cells retrogradely labeled
following WGA-HRP injections into the contralateral superior
colliculus. In monkeys, labeled tectotectal cells were
found in all layers, but were concentrated in the intermediate
gray layer (75%), particularly dorsally, and the adjacent
optic layer (12%). Tectotectal cells were distributed throughout
nearly the entire rostrocaudal extent of the colliculus.
In cats, tectotectal cells were found in all the layers
beneath the superficial gray, but the intermediate gray
layer contained the greatest concentration (56%). Labeled
cells were almost exclusively located in the rostral half
of the cat superior colliculus, in contrast to the monkey
distribution. In the context of the representation of visuomotor
space in the colliculus, the distribution of monkey and
cat tectotectal cells suggests a correspondence with oculomotor
range. So these neurons may be involved in directing orienting
movements performed within the oculomotor range. The somatodendritic
morphology of tectotectal cells in these two species was
revealed by homogeneous retrograde labeling from injections
of biocytin or biotinylated dextran amine into the contralateral
colliculus. The cell classes contributing to this pathway
are fairly consistent across the two species. A variety
of neuronal morphologies were observed, so there is no
single tectotectal cell type. Instead, cell types similar
to those found in each layer, excepting the largest neurons,
were present among tectotectal cells. This suggests that
a sample of each layer's output is sent to the contralateral
colliculus.
Cytochrome-oxidase blobs and intrinsic horizontal connections
of layer 2/3 pyramidal neurons in primate V1
Authors: YABUTA NEUSA H. , CALLAWAY EDWARD M.
Published: July 2002

Pyramidal neurons in superficial layers of cerebral
cortex have extensive horizontal axons that provide a substrate
for lateral interactions across cortical columns. These
connections are believed to link functionally similar regions,
as suggested by the observation that cytochrome-oxidase
blobs in the monkey primary visual cortex (V1) are preferentially
connected to blobs and interblobs to interblobs. To better
understand the precise relationship between horizontal
connections and blobs, we intracellularly labeled 20 layer
2/3 pyramidal neurons in tangential living brain slices
from V1 of macaque monkeys. The locations of each cell
body and the cell's synaptic boutons relative to blobs
were quantitatively analyzed. We found evidence for two
cell types located at characteristic distances from blob
centers: (1) neurons lacking long-distance, clustered axons
(somata 130–200 μm from blob centers) and (2)
cells with clustered, long-distance axon collaterals (somata
<130 μm or >200 μm from blob centers). For
all cells, synaptic boutons close to the cell body were
located at similar distances from blob centers as the cell
body. The majority of boutons from cells lacking distal
axon clusters were close to their cell bodies. Cells located
more than 200 μm from blob centers were in interblobs
and had long-distance clustered axon collaterals selectively
targeting distant interblob regions. Cells located less
than 130 μm from blob centers were found within both
blobs and interblobs, but many were close to traditionally
defined borders. The distant synaptic boutons from these
cells were generally located relatively near to blob centers,
but the neurons closest to blob centers had synaptic boutons
closer to blob centers than those farther away. There was
not a sharp transition that would suggest specificity for
blobs and interblobs as discrete, binary entities. Instead
they appear to be extremes along a continuum. These observations
have important implications for the function of lateral
interactions within V1.
Does rod phototransduction involve the delayed transition of
activated rhodopsin to a second, more active catalytic state?
Authors: PEPPERBERG DAVID R.
Published: July 2002

Recovery kinetics of the saturating photocurrent
response in amphibian rods suggest regulation of the visual
signal by a first-order deactivation reaction with an exponential
time constant (τc) of about 2 s. The original
hypothesis that τc represents the lifetime
of activated rhodopsin (R*) in a single-step
deactivation appears at odds with several recent findings,
for example, that Ca2+, a known regulator of
the enzymatic phosphorylation of R*, does not
regulate the value of τc. A recently proposed
alternative hypothesis, that τc is the lifetime
of activated transducin and that the R* lifetime
is relatively short (∼0.4 s), appears consistent with
the Ca2+ data but is difficult to reconcile
with a high specific catalytic activity of R*.
The present theoretical study proposes a rate-equation
model of R* activation and deactivation in amphibian
rods that is generally consistent with observed properties
of the τc-associated reaction and the action
of Ca2+ as well as with the stereotyped nature
of the single-photon response. The model is developed by
considering the effect of background light on a time-dependent
variable, Reff*,
defined as the effective total level of R*
activity. Central starting assumptions are that Ca2+
reduction mediates the effect of background light on Reff*(t) and
that background desensitization of the photocurrent flash
response derives from this action of Ca2+. Construction
of the model is guided by criteria based on previous experimental
findings. Among these are the approximate constancy of
background desensitization expressed at near-peak and later
times in the flash response, and the large (∼10-fold)
dynamic range of this desensitization. The proposed model
hypothesizes that an event regulated by Ca2+
feedback causes activated rhodopsin to become susceptible
to a two-phase, stochastic deactivation process, the second
phase of which is characterized by τc. A
central prediction of the model is the regulated transition
of flash-activated R* to “R**”,
a state exhibiting greatly increased catalytic activity.
Increased serotonin in the developing superior colliculus
affects receptive-field size of retinotectal afferents
but not that of postsynaptic neurons
Authors: KE MIN , MOONEY RICHARD D. , RHOADES ROBERT W.
Published: July 2002

Administration of a single subcutaneous dose of
5,7-dihydroxytryptamine (5,7-DHT) to newborn hamsters results
in a significant increase in the density of serotoninergic
(5-HT) fibers in the superficial layers of the superior
colliculus (SC) and marked abnormalities in the uncrossed
retinotectal projection when these animals reach adulthood
(Rhoades et al., 1993). The present study was undertaken
to determine whether elevation of 5-HT in the developing
SC altered the visual representation in SC. Multi-unit
recordings from SC cells demonstrated that the overall
organization of the visual map in the superficial SC laminae
was normal and that the receptive-field sizes for unit
clusters were unchanged in the 5,7-DHT-treated animals.
However, when a combination of CNQX and MK-801 was directly
applied to the SC to block postsynaptic activity, the receptive
fields of unit clusters (presumably retinotectal axon terminals)
in the 5,7-DHT treated animals were significantly larger
than those in the normally reared hamsters. These results
are consistent with the conclusions that elevation of 5-HT
levels in the developing SC reduces the postnatal refinement
of the crossed retinotectal axons, and that mechanisms
operating within the SC may act to maintain normal sizes
for the receptive fields of its constituent neurons.
Suppression of voltage-dependent K+ currents
in retinal bipolar cells by ascorbate
Authors: FAN SHIH-FANG , YAZULLA STEPHEN
Published: July 2002

Ascorbate, often used as an antioxidant in neural
studies, may also serve as a neuromodulator in the vertebrate
central nervous system (CNS), in that it modulates the
synaptic actions of glutamate and dopamine. Retina of fish
contain a high concentration of ascorbate. The release
and/or uptake of neurotransmitters are related to membrane
potential, which to a large extent is determined by the
activity of K+ channels. As retinal bipolar
cells are subject to synaptic input from glutamatergic
and dopaminergic sources, the effects of ascorbate on voltage-dependent
K+ currents (IK(V)) of the
mixed rod–cone ON-center bipolar cells (Mb) in goldfish
retinal slices were studied using whole-cell recording
techniques. IK(V) was suppressed reversibly
60% by 100–200 μM ascorbate. The effect of ascorbate
was not due to changes in pH, oxidative stress, lipid peroxidation,
any Ca2+-dependent or Na+-dependent
action. However, the suppressive effect of ascorbate was
blocked by cholera toxin and Wiptide, a protein kinase
A (PKA) inhibitor. It is concluded that ascorbate, at physiological
concentrations, inhibits IK(V) of bipolar
cells via a GS-protein-PKA system.
This effect of ascorbate should be taken into account when
using ascorbate as an antioxidant in retinal studies involving
dopamine.
Sub-millimolar cobalt selectively inhibits the receptive
field surround of retinal neurons
Authors: VIGH JOZSEF , WITKOVSKY PAUL
Published: July 2002

Recent work has indicated that cobalt, at sub-millimolar
concentrations, blocks horizontal cell (HC) to cone feedback,
without attenuating direct cone to second-order cell synaptic
transmission. We utilized low concentrations (0.25–0.5
mM) of cobalt to test the contribution of the feedback
circuit, and other possible cobalt-sensitive mechanisms,
to the receptive-field surrounds of retinal neurons. In
the great majority of cases, low cobalt blocked ganglion
cell surrounds, and it invariably blocked driving the ganglion
cell by extrinsic current injected into the HC network.
Although low cobalt reduced the integrating area of the
HC network, dopamine, which similarly constricted the HC
receptive area, did not block ganglion cell surrounds.
Low cobalt reduced a late depolarizing wave in the HC light-evoked
waveform and selectively suppressed the depolarizing component
of chromatic HCs, both signs of HC to cone feedback. Low
cobalt also reduced or blocked completely the receptive-field
surrounds of a small sample of bipolar and amacrine cells.
These results implicate the HC to cone feedback synapse
in the formation of the receptive-field surround of retinal
neurons.
Responses of directionally selective retinal ganglion cells
to activation of AMPA glutamate receptors
Authors: JENSEN RALPH J.
Published: July 2002

Previous studies in the rabbit retina have shown
that drugs which block AMPA glutamate receptors abolish
directional selectivity in ON–OFF directionally selective
(DS) ganglion cells. The effects of activation of AMPA
receptors on the directionally selective responses of these
ganglion cells had not been studied. In the present study,
extracellular recordings of the responses of ON–OFF
DS ganglion cells to a moving bar of light were made in
an in vitro rabbit retinal preparation. In control
solution, bath application of AMPA (7–10 μM)
abolished the light responses of most ON–OFF DS ganglion
cells. On washout of AMPA, the light responses rapidly
returned; however, the cells temporarily lost the ability
to discriminate the direction of the moving bar of light.
That is, the cells responded equally to movement in the
preferred and null directions. Pretreatment of retinas
with the glycine receptor antagonist strychnine (1–2
μM) did not alter the effects of AMPA. On the other
hand, in retinas pretreated with the GABAA receptor
antagonist SR95531 (0.2–0.25 μM), AMPA did not
abolish the light responses of ON–OFF DS ganglion
cells but instead abolished directional selectivity in
these cells by bringing out a response to movement in the
null direction. This finding suggests that an AMPA-induced
GABA efflux from cells in the retina was responsible for
the suppression of the light responses by AMPA. In control
solution, application of the selective AMPA receptor agonist
(S)-5-fluorowillardiine (2–3 μM) only temporarily
abolished the light responses of ON–OFF DS ganglion
cells. As the light responses returned, it was clear that
directional selectivity had been abolished by (S)-5-fluorowillardiine.
In control solution, blocking AMPA receptor desensitization
with cyclothiazide (80–100 μM) greatly reduced
the light responses of ON–OFF DS ganglion cells.
As the light responses slowly returned on washout of cyclothiazide,
directional selectivity was clearly reduced although not
abolished. In retinas pretreated with SR95531, application
of cyclothiazide abolished directional selectivity. Diazoxide
(700–1000 μM), another blocker of AMPA receptor
desensitization, abolished directional selectivity in ON–OFF
DS ganglion cells without the need of adding SR95531 to
the bathing solution. It is concluded that, in the rabbit
retina, AMPA receptors play an important role in generating
directional selectivity in ON–OFF DS ganglion cells.
Moreover, excessive activation of AMPA receptors greatly
compromises the mechanism for directional selectivity in
ON–OFF DS ganglion cells.
Effects of inhibiting glutamine synthetase and blocking
glutamate uptake on b-wave generation in the isolated
rat retina
Authors: WINKLER BARRY S. , KAPOUSTA-BRUNEAU NATALIA , ARNOLD MATTHEW J. , GREEN DANIEL G.
Published: July 2002

The purpose of the present experiments was to evaluate
the contribution of the glutamate-glutamine cycle in retinal
glial (Müller) cells to photoreceptor cell synaptic
transmission. Dark-adapted isolated rat retinas were superfused
with oxygenated bicarbonate-buffered media. Recordings
were made of the b-wave of the electroretinogram
as a measure of light-induced photoreceptor to ON-bipolar
neuron transmission. L-methionine sulfoximine (1–10
mM) was added to superfusion media to inhibit glutamine
synthetase, a Müller cell specific enzyme, by more
than 99% within 5–10 min, thereby disrupting the
conversion of glutamate to glutamine in the Müller
cells. Threo-hydroxyaspartic acid and D-aspartate were
used to block glutamate transporters. The amplitude of
the b-wave was well maintained for 1–2 h
provided 0.25 mM glutamate or 0.25 mM glutamine was included
in the media. Without exogenous glutamate or glutamine
the amplitude of the b-wave declined by about
70% within 1 h. Inhibition of glutamate transporters led
to a rapid (2–5 min) reversible loss of the b-wave
in the presence and absence of the amino acids. In contrast,
inhibition of glutamine synthetase did not alter significantly
either the amplitude of the b-wave in the presence
of glutamate or glutamine or the rate of decline of the
b-wave found in the absence of these amino acids.
Excellent recovery of the b-wave was found when
0.25 mM glutamate was resupplied to L-methionine sulfoximine–treated
retinas. The results suggest that in the isolated rat retina
uptake of released glutamate into photoreceptors plays
a more important role in transmitter recycling than does
uptake of glutamate into Müller cells and its subsequent
conversion to glutamine.