Biomedical subjects

A S Ramoa

Publications and source records attributed to A S Ramoa.

At least 19 recordsLinked to original sources

PubMed2001

Do NMDA receptor kinetics regulate the end of critical periods of plasticity?

Increasing NR2A subunit expression and the associated shortening of the NMDA-EPSC are thought to underlie the loss of diverse types of sensory cortical plasticity. Lu and colleagues (Lu et al., 2001 [this issue of Neuron]) now report that mice lacking the NR2A subunit display normal duration of critical periods of barrel cortex plasticity. Shortening of the NMDA-EPSC is therefore not responsible for the end of these critical periods.

Animals↗

PubMed2001

Suppression of cortical NMDA receptor function prevents development of orientation selectivity in the primary visual cortex.

Selectivity to visual stimulus orientation is a basic cortical functional property believed to be crucial for normal vision. Maturation of this neuronal property requires neural activity. Still, it is unclear what might be the molecular basis for such activity-dependent processes and whether activity has an instructive or permissive role in development of orientation selectivity. There is strong evidence that the NMDA subtype of the glutamate receptor regulates activity-dependent mechanisms of ocular dominance plasticity during cortical development. For this reason, we have hypothesized that the NMDA receptor participates in activity-dependent mechanisms that sculpt orientation selectivity of cortical neurons. We used chronic in vivo infusion of antisense oligodeoxynucleotides (ODNs) to suppress NMDA receptor function in primary visual cortex during the period when orientation selectivity develops in ferrets. Chronic suppression of NMDA receptor function prevented the development of orientation and stimulus size selectivity in most cortical cells tested. In contrast, treatment with control sense or missense ODNs did not affect development of orientation selectivity, indicating specificity of effects. Importantly, antisense ODN treatment did not impair visually driven activity, which is required for development to occur. Moreover, orientation selectivity of cortical cells was not disrupted by antisense ODN treatment in mature animals, indicating developmental relevance of the effects. In conclusion, our findings document for the first time that cortical NMDA receptors are essential for the maturation of orientation selectivity. This result supports the notion that activity has an instructive role in sculpting the connections that underlie orientation selectivity in visual cortex.

Aging↗

PubMed2001

Organization of the neurons of origin of the descending pathways from the ferret superior colliculus.

The superior colliculus (SC), through its descending projections to the brainstem and spinal cord, is involved in initiating sensory-driven orienting behaviors. Ferrets are carnivores that hunt both above and below ground using visual (and auditory) cues in the daylight but non-visual cues in darkness and in subterranean environments. The present investigation sought to determine whether the ferret SC shows organizational features similar to those found in other visually dominant animals (e.g. cats), or whether characteristics of colliculi from non-visually dominant animals (e.g. rodents) prevail. Injection of retrograde tracer into the identified targets of the colliculus (cervical spinal cord, the contralateral pontomedullary reticular formation, or the ipsilateral pontine reticular formation) labeled tectospinal, crossed tectoreticular, and ipsilateral tectoreticular neurons, respectively, within the adult ferret SC. Labeled tectospinal and crossed tectoreticular neurons were far outnumbered by neurons with ipsilateral reticular projections. Like those of their visually dominant relatives, ferret tectospinal neurons were well represented throughout the anterior-posterior extent of the SC and crossed tectoreticular neurons tended to be distributed more broadly across the intermediate gray layer than those of rodents. Thus, even though ferrets perform well as subterranean predators where non-visual cues initiate orienting behaviors, these anatomical characteristics indicate that their colliculi are organized similar to that of their visually dominant, carnivorous relatives.

Animals↗

PubMed1999

Novel method of chronically blocking retinal activity.

The ethylene-vinyl acetate copolymer Elvax has been used as a vehicle to deliver bioactive substances to discrete areas of the nervous system. Here we report a novel use of Elvax to chronically block retinal activity. Small pieces of Elvax containing the sodium channel blocker tetrodotoxin (TTX) were surgically implanted into the vitreous humor of ferret eyes. Observations of the light-induced pupillary reflex combined with electrophysiological assays of vitreous humor confirmed that these implants completely blocked retinal activity for up to 25 days without apparent retinal damage. The advantages of this procedure over previous methods requiring multiple daily injections of TTX, and alternative experimental applications are discussed.

Action Potentials↗

PubMed1999

Enhanced NR2A subunit expression and decreased NMDA receptor decay time at the onset of ocular dominance plasticity in the ferret.

Enhanced NR2A subunit expression and decreased NMDA receptor decay time at the onset of ocular dominance plasticity in the ferret. The NMDA subtype of glutamate receptor is known to exhibit marked changes in subunit composition and functional properties during neural development. The prevailing idea is that NMDA receptor-mediated synaptic responses decrease in duration after the peak of cortical plasticity in rodents. Accordingly, it is believed that shortening of the NMDA receptor-mediated current underlies the developmental reduction of ocular dominance plasticity. However, some previous evidence actually suggests that the duration of NMDA receptor currents decreases before the peak of plasticity. In the present study, we have examined the time course of NMDA receptor changes and how they correlate with the critical period of ocular dominance plasticity in the visual cortex of a highly binocular animal, the ferret. The expression of NMDA receptor subunits NR1, NR2A, and NR2B was examined in animals ranging in age from postnatal day 16 to adult using Western blotting. Functional properties of NMDA receptors in layer IV cortical neurons were studied using whole cell patch-clamp techniques in an in vitro slice preparation of ferret primary visual cortex. We observed a remarkable increase in NR1 and NR2A, but not NR2B, expression after eye opening. The NMDA receptor-mediated synaptic currents showed an abrupt decrease in decay time concurrent with the increase in NR2A subunit expression. Importantly, these changes occurred in parallel with increased ocular dominance plasticity reported in the ferret. In conclusion, molecular changes leading to decreased duration of the NMDA receptor excitatory postsynaptic current may be a requirement for the onset, rather than the end, of the critical period of ocular dominance plasticity.

Aging↗

PubMed1998

Intrinsic circuitry of the superior colliculus: pharmacophysiological identification of horizontally oriented inhibitory interneurons.

Much of what is known about the organization of the superior colliculus is based on the arrangement of its external connections. Consequently, there is little information regarding pathways that remain intrinsic to it, even though recent data suggest that a horizontally oriented local circuit may mediate the functional reciprocity among fixation and saccade-related neurons. Therefore, the present experiments sought physiological evidence for neurons intrinsic to the superior colliculus that might participate in a horizontally oriented local circuit. Parasagittal slices of the ferret superior colliculus were prepared for in vitro recording, and 125 intermediate/deep layer neurons were examined in response to electrical stimulation rostral or caudal to the recording site. A substantial proportion (37%) of neurons responded with a prolonged period (means = 59.3 +/- 30 ms) of poststimulus suppression of spontaneous action potential activity. Of the suppressed neurons, most (53%) were disinhibited when the excitatory amino acid receptor antagonists D-2-amino-5-phosphonovaleric acid (D-APV) and 6-nitro-7 sulphamoylbeno[f]-quinoxaline-2,3-dione (NBQX) were administered, indicating that excitatory input to inhibitory interneurons was blocked. Of the neurons that received inputs from inhibitory interneurons, all had their suppressive responses decreased or eliminated by the gamma-aminobutyric acid antagonist, bicuculline. Finally, severing the superficial layers from the slice had no effect on intermediate layer responses to intrinsic stimulation. These data provide physiological evidence for the presence of horizontally oriented inhibitory interneurons in the superior colliculus. Furthermore, these findings are consistent with the hypothesis that an intrinsic circuit, routed through interneurons, might account for the reciprocal inhibition observed among fixation and saccade-related neurons.

2-Amino-5-phosphonovalerate↗

PubMed1998

Suppression of NMDA receptor function using antisense DNA block ocular dominance plasticity while preserving visual responses.

Pioneering work has shown that pharmacological blockade of the N-methyl-D-aspartate (NMDA) receptor channel reduces ocular dominance plasticity. However, the results also show that doses of NMDA receptor antagonists that have an effect on ocular dominance plasticity profoundly reduce sensory responses and disrupt stimulus selectivity of cortical cells. It is, therefore, not possible to determine whether effects of NMDA receptor blockade on visual plasticity result from a specific role of NMDA receptors or from the reduction in sensory response. We have used an alternate approach to examine this question. We performed knockdown experiments using antisense oligodeoxynucleotides (ODNs) complementary to mRNA coding the NR1 subunit of the NMDA receptor. After 5 days of antisense, but not sense, ODN treatment NMDA receptor-mediated synaptic transmission was reduced markedly relative to the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor response, as indicated by whole cell patch-clamp recordings in the cortical slice preparation. This suppression of NMDA receptor-mediated currents was due to a selective reduction in the NR1 protein near the injection site relative to the untreated hemisphere in the same animal, as indicated by immunocytochemistry and Western blotting. In contrast, AMPA receptors were not affected by the antisense ODN treatment indicating specificity of effects. Another major effect of this treatment was to decrease ocular dominance plasticity. Ferrets that were monocularly deprived 1 wk during the antisense ODN treatment had ocular dominance histograms similar to those found in untreated, nondeprived animals. In contrast, ferrets treated with sense ODN and monocularly deprived had ocular dominance histograms resembling those of untreated, monocularly deprived animals. The effects on ocular dominance plasticity did not result from a disruption of sensory responses because maximum responses as well as orientation and direction selectivity of cortical cells were not affected by the treatment. In conclusion, the present results show that antisense techniques can accomplish more selective manipulations of cortical function than is possible with traditional pharmacological agents. Use of this approach also provides unambiguous evidence for a specific role of NMDA receptors in visual plasticity.

2-Amino-5-phosphonovalerate↗

PubMed1997

Retinal activity regulates developmental switches in functional properties and ifenprodil sensitivity of NMDA receptors in the lateral geniculate nucleus.

Previous studies have shown that marked changes occur in the kinetic properties of N-methyl-D-aspartate (NMDA) receptors during development of the visual pathways. In the lateral geniculate nucleus (LGN) of the ferret, excitatory postsynaptic currents (EPSCs) induced by activation of NMDA receptors display a very slow decay time during the first postnatal month, then become shorter in duration following eye-opening (around postnatal day 32; P32). In view of the critical role that NMDA receptors play in activity-dependent refinement of visual connections during development, we have examined the mechanisms that underlie these changes and how they are regulated. To examine the role of retinal activity, whole-cell recordings were conducted in the LGN slice preparation obtained from normal ferrets and ferrets treated with continuous intraocular application of tetrodotoxin (TTX) from P25 until the time of recording. Blockade of ganglion cell activity with TTX prevented the changes in decay rate of the postsynaptic current induced by NMDA receptors. Treated animals older than P40 had NMDA-EPSCs markedly longer in duration than normal animals at a similar age, resembling responses present in normal newborn animals. To examine whether changes in subunit composition of the NMDA receptor may contribute to the maturation of its kinetic properties, we used the antagonist ifenprodil, which produces selective inhibition of heteromeric NMDA receptors containing the NR-2B subunit. Ifenprodil induced profound inhibition of NMDA receptor activity in normal young animals and TTX-treated mature animals, but substantially less inhibition in normal mature animals. These findings indicate that retinal activity is required for the developmental switch from a juvenile form of the NMDA receptor to a more mature form, possibly affecting NR2 subunit expression.

Action Potentials↗

PubMed1996

Transient retinal ganglion cells in the developing rat are characterized by specific morphological properties.

To determine whether dendritic development of mammalian retinal ganglion cells (RGCs) is affected by axonal target specificity, the morphology of three populations of maturing RGCs was examined. These included RGCs that exhibited either a transient, topographically incorrect, projection to the caudal superior colliculus (SC), or a transient projection to the caudal inferior colliculus (IC), in addition to a control group that exhibited a topographically correct projection to the caudal SC. Projection populations were identified by retrograde transport of rhodamine labeled latex microspheres injected into target nuclei. Labeled RGCs were then injected in vitro with Lucifer yellow to reveal the details of their dendritic morphology. Retinal ganglion cells making target errors, most of which ultimately die, were found to undergo a remarkable degree of morphological differentiation and could be categorized according to the adult type I, II, or III criteria. However, the relative proportions of these cell types were different among RGCs making transient connections versus those whose projections were preserved. Approximately half of the RGCs making topographically incorrect projections to the SC belonged to type III, in contrast to 6% that made a topographically correct projection. In addition, the population of cells sending axons to caudal IC did not include type III RGCs, but consisted of small type II neurons. The development of the basic dendritic form of each RGC type was only modestly influenced by its projection pattern; dendritic trees of cells making transient projections were essentially normal with only a slight, but statistically significant, reduction in dimensions. Moreover, dendritic remodeling was evident during maturation of neurons making either transient or normal projections. Together, these findings indicate that target specificity plays a relatively minor role on dendritic development of retinal ganglion cells.

Animals↗

PubMed1995

Postnatal development of synchronized network oscillations in the ferret dorsal lateral geniculate and perigeniculate nuclei.

Extracellular and intracellular recordings from slices of ferret dorsal lateral geniculate nucleus (LGNd) at postnatal ages P10-53 were performed to examine the postnatal development of spindle waves and the ability of block of GABAA receptors to alter these spindle waves into a slower, synchronous oscillation. As in prior studies in the adult, intracellular and extracellular recordings at ages P33-53 revealed robust spindle waves to be present in both the LGNd and perigeniculate nucleus (PGN). Intracellular recordings from thalamocortical relay cells in the A-laminae of the LGNd revealed that these cells received repetitive inhibitory postsynaptic potentials (IPSPs) at 6-9 Hz during the generation of spindle waves, and generated rebound low threshold Ca2+ spikes and bursts of 2-6 action potentials following each second or third IPSP. Intracellular recordings from the GABAergic neurons of the PGN at P33-53 revealed barrages of EPSPs that activated low threshold Ca2+ spikes and high frequency burst discharges of 2-10 action potentials during spindle wave generation. In contrast, full spindle waves were absent at ages prior to approximately P22 and spindle waves between the ages of P26 and approximately P30 were relatively weak and associated with only one or two action potentials per burst in both PGN neurons and LGNd relay cells. Bath application of the GABAA antagonist bicuculline methiodide at P41-53 resulted in a conversion of normal spindle waves into a marked 2-4 Hz oscillation in which the action potential firing of both thalamocortical relay and PGN neurons was greatly increased. In contrast, block of GABAA receptors prior to age P39 did not result in the generation of the slowed, 2-4 Hz network oscillation. Investigation of the electrophysiological properties of PGN neurons revealed that the postnatal development of spindle waves and bicuculline-induced slow oscillations were associated with an increase in the ability of PGN neurons to generate high frequency bursts of action potentials, suggesting that these changes in electrophysiological properties may contribute to the late development of synchronized oscillations in the ferret LGNd.

Aging↗

PubMed1994

Enhanced activation of NMDA receptor responses at the immature retinogeniculate synapse.

The maturation of retinogeniculate excitatory transmission and intrathalamic inhibition was studied in slices of the dorsal LGN obtained from ferrets during the first 2 postnatal months. Response to optic tract stimulation at neonatal ages consisted of slow EPSPs lasting several hundred milliseconds. Application of the NMDA receptor antagonist D-(-)-2-amino-5-phosphonovaleric acid (D-APV) during the first 2 postnatal weeks resulted in EPSPs that were reduced in peak amplitude and dramatically curtailed in duration, indicating that NMDA receptors participate strongly in retinogeniculate transmission at the immature synapse. Gradually, EPSPs became shorter in duration such that after the second postnatal week, the retinogeniculate EPSPs were only a few milliseconds in duration. At this late stage of development responses were remarkably less affected by application of D-APV. These changes in contribution of NMDA receptors to retinogeniculate transmission were found to be due to the development of strong IPSPs, the result of gradual maturation of activation of GABAergic inhibition. Indeed, application of bicuculline methiodide to block GABAA receptor-mediated IPSPs strongly enhanced the NMDA component of the EPSPs in more mature cells. The voltage dependence and kinetics of NMDA-induced excitatory postsynaptic currents (NMDA EPSCs) were characterized by voltage-clamp recordings after blocking AMPA/kainate receptors with 6-cyano-7-nitroquinoxaline-2,3-dione and GABAA receptors wit' bicuculline methiodide. The voltage dependence of the NMDA EPSCs remained unaltered with age. During the first postnatal month the kinetic properties of the NMDA EPSCs also remained unaltered, but a reduction in EPSC duration was observed within the following weeks, well after the critical period of anatomical reorganization.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1994

Developmental changes in electrophysiological properties of LGNd neurons during reorganization of retinogeniculate connections.

Changes in electrophysiological properties of neurons in the ferret dorsal LGN (LGNd) were studied during early postnatal life, a critical developmental period when changes occur in morphology, connectivity, and response properties of LGNd neurons. Using the patch-clamp technique to obtain whole-cell recordings from cells maintained as in vitro slices of thalamus, several distinctive properties were observed in the immature LGNd. Relatively low resting membrane potentials were present that became more negative during the first 2 postnatal weeks. In addition, immature neurons exhibited high input resistances that decreased during early postnatal development. At all ages postnatally, neurons were capable of generating a train of Na(+)-dependent action potentials in response to intracellular injection of a depolarizing current pulse. Moreover, immature neurons resembled older cells in that little spike frequency adaptation was present during a train of action potentials. Action potential activity in immature neurons was nevertheless distinctive in several respects: (1) during the first 2-3 postnatal weeks action potentials became shorter in duration and larger in amplitude; (2) during the same period, thresholds for generation of action potentials changed in conjunction with the changes in resting membrane potential, becoming more negative; and (3) plots of frequency versus injected current revealed that thresholds for generation of trains of action potentials were reached with intracellular injection of lower current levels at earlier ages. These findings raise the possibility that relatively weak ionic currents generated at immature synapses have unexpectedly strong effects on the young LGNd neuron.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1993

Dendritic remodelling of retinal ganglion cells during development of the rat.

Investigation of the morphology of ganglion cells in the cat retina has shown that a remarkable reduction in the number of dendritic spines and branches occurs during development of the alpha and beta cell classes. To learn whether dendritic remodelling represents a generalized mechanism of mammalian retinal ganglion cell development, we have examined the morphology of ganglion cells in the retina of the developing rat. The present study has concentrated on type II cells, which retain a great number of dendritic spines and branches in the adult and comprise a large proportion of the population of rat retinal ganglion cells. To reveal fine dendritic and axonal processes, Lucifer yellow was injected intracellularly in living retinae maintained in vitro. Size and complexity of the dendritic trees were found to increase rapidly during an initial stage of development lasting from late fetal life until approximately postnatal day 12 (P12). Dendrites and axons of immature ganglion cells expressed several transient morphological features comprising an excessive number of dendritic branches and spine-like processes, and short, delicate axonal sidebranches. The following developmental stage was characterized by a remarkable decrease in the morphological complexity of retinal ganglion cells and a slowed growth of their dendritic fields. The number of dendritic branches and spines of types I and II retinal ganglion cells declined after P12 to reach a mature level by the end of the first postnatal month. Thus, even cells that retain a highly complex dendritic tree into the adult state undergo extensive remodelling. These results suggest that regressive modifications at the level of the dendritic field constitute a generalized mechanism of maturation in mammalian retinal ganglion cells.

Animals↗

PubMed1991

Functional properties of the nicotinic and glutamatergic receptors.

Several important physiological processes such as plasticity, memory, cell death, and rhythmic firing involve the N-methyl-D-aspartate (NMDA)-type of glutamatergic receptor. Nicotinic acetylcholine receptors (AChR), recently demonstrated in the central nervous system (CNS), are also of great interest. We have used several ligands to study the physiology and pharmacology of the agonist recognition sites of these receptors and kinetic properties of associated ion channels using whole-cell, cell-attached or outside-out variants of the patch-clamp technique. Enzymatically dissociated frog interosseal muscles were used to study peripheral AChRs, and tissue cultured or acutely dissociated hippocampal neurons and retinal ganglion cells (RGCs) for CNS receptors. For reproducible and fast solution changes when recording in the whole-cell configuration, we modified the "U"-shaped tube system to obtain different outputs from the same outflow port. We used fluorescent rhodamine-labeled latex microspheres to identify RGCs. Our studies provide important information regarding the molecular mechanisms of several clinically used agents. Additionally, similar actions of noncompetitive agents on the ion channels of the nicotinic ACh and NMDA receptors support the concept of a receptor ion channel superfamily.

Animals↗

PubMed1990

The anticonvulsant MK-801 interacts with peripheral and central nicotinic acetylcholine receptor ion channels.

The effects of MK-801 [( +]-5-methyl-10,11-dihydro-5H-di-benzo[a, d]cyclohepten-5,10-imine) on peripheral and central nicotinic receptors were studied using electrophysiological and biochemical techniques. MK-801 depressed the peak amplitude and accelerated the decay of end-plate currents. The drug (1-10 microM) decreased the frequency of activation of acetylcholine (ACh)-induced single-channel currents in addition to shortening the mean open and burst times of channels activated by either ACh or (+)anatoxin-a (AnTX). MK-801 (10-40 microM) depressed the single potentials and trains of ACh and AnTX-induced potentials in chronically denervated rat soleus muscles. MK-801 blocked the twitch responses (20-100 microM) of both frog sartorius and rat diaphragm muscles evoked by stimulation of their respective nerves. Also this drug (less than 1 microM) decreased the frequency of channels activated by AnTX or ACh in outside-out patch membranes of rat retinal ganglion cells with minimal changes in the channel open time. MK-801 (10-25 microM) depressed (-)nicotine-evoked gamma-amino[2,3-3H]butyric acid release from rat hippocampal synaptosomes; however, it failed to affect the binding of [3H](-)nicotine to brain membranes and also failed to interfere with the binding of [125I]alpha-bungarotoxin to either frog muscle or Torpedo membranes. On the other hand, MK-801 inhibited the binding of [3H]perhydrohistrionicotoxin to Torpedo membranes and such an effect was more pronounced in the presence of carbamylcholine. Neither AnTX nor any other nicotinic agonist increased the binding of [3H]MK-801 to the N-methyl-D-aspartate receptor ion channel complex. The actions of MK-801 were evident at concentrations comparable with those needed to block N-methyl-D-aspartate receptors. These results demonstrate the existence of at least three different types of nicotinic AChR, all of which were blocked noncompetitively by MK-801.

Acetylcholine↗

PubMed1989

Retinal ganglion beta cells project transiently to the superior colliculus during development.

In adult cats, retinal ganglion cells of the beta class project almost exclusively to the lateral geniculate nucleus rather than to the superior colliculus (SC). We have examined whether this target specificity is present during early development. To identify ganglion cells that send axons to the SC in development, rhodamine-labeled microspheres were deposited in the SC at embryonic day (E) 38, E43, or postnatal day (P) 4. Retinae were then removed between E56 and P32 and kept alive in a tissue-slice chamber so that ganglion cells that had been retrogradely labeled with microspheres could be injected intracellularly with Lucifer yellow to reveal their morphological class. Many beta cells could be retrogradely labeled by microspheres injected into the SC at E38 or E43. They were indistinguishable from beta cells projecting to the lateral geniculate nucleus and were found even when a single injection was restricted to the caudal portion of the SC. In contrast, beta cells could not be retrogradely labeled by microspheres injected into the SC at P4. The disappearance of a beta-cell projection to the SC cannot be explained entirely by cell death since as late as P32, well after the major period of ganglion cell death, many beta ganglion cells labeled with microspheres at E38 were still present. These observations suggest that many beta cells initially extend an axon collateral to the SC that is subsequently lost some time after E43. Thus, to achieve the remarkable specificity present in the adult visual system, beta cells must withdraw axon collaterals from an entire target nucleus. Similar collateral elimination may give rise to the specificity of afferent connections in other sensory systems.

Animals↗

PubMed1988

Phencyclidine and some of its analogues have distinct effects on NMDA receptors of rat hippocampal neurons.

Phencyclidine (PCP) is a dissociative anesthetic agent which blocks the excitatory effect of N-methyl-D-aspartate (NMDA) in the central nervous system. To investigate the role of the PCP reactive site in the control of NMDA activation of hippocampal pyramidal cells, we have examined the action of PCP and some of its analogues on the response properties of single NMDA receptors. Application of NMDA (5-15 microM) to outside-out patches of membrane elicited bursts of ion channel openings which were greatly reduced in frequency and duration in the presence of PCP (2.5-10 microM) or m-amino-PCP (2.5-10 microM), a behaviorally active derivative of PCP. These effects of PCP were reversed when the membrane potential was shifted from negative to positive values. Application of the behaviorally inactive agent 1-piperidino-cyclohexanecarbonitrile (greater than or equal to 220 microM) left NMDA-activated currents relatively unaltered. Treatment with another analogue, m-nitro-PCP (5-20 microM), resulted in an unexpected increase in frequency of openings. At a higher concentration (100-300 microM), however, m-nitro-PCP acted like PCP in reducing frequency of opening and channel life-time. Like PCP, these effects of m-nitro-PCP were reversed at positive potentials. Taken together, these results suggest that PCP and its derivatives block the open state of the NMDA channel. Moreover, the dual effect of m-nitro-PCP shows that excitability is not necessarily decreased by PCP analogues but may instead be enhanced depending on modifications of the PCP molecule.

Animals↗

PubMed1988

Binocular interaction in the perigeniculate nucleus of the cat.

We have recorded from single cells in the perigeniculate nucleus (PGN) of the cat to determine their response properties. Quantitative tests have been conducted with sinusoidal gratings. Using optimal stimulus parameters, determined monocularly, we explored binocular interaction by varying the relative phase between dichoptically presented gratings. Monocularly, cells exhibit varying degrees of response specificities with respect to stimulus orientation and spatial frequency. Binocularly, we have identified six types of response. The most prominent, type 1, found for half the cells, is phase-specific binocular interaction at the fundamental frequency component of the drifting grating. For these cells, mean response rate is independent of interocular phase. The remaining types of binocular responses involve varying degrees of interaction at different harmonic components. For a quarter of the sample, no binocular interaction was observed. To investigate the role of cortical input to PGN, visual cortex was removed from some cats. Subsequent study of PGN cells indicated that response properties were generally similar to those found in intact animals. We conclude that PGN response properties are determined primarily by subcortical inputs.

Afferent Pathways↗