NMDA Receptor Blockade in the Superior Colliculus Increases Receptive Field Size Without Altering Velocity and Size Tuning

2003 ◽  
Vol 90 (1) ◽  
pp. 110-119 ◽  
Author(s):  
Khaleel A. Razak ◽  
Lihua Huang ◽  
Sarah L. Pallas
Keyword(s):  
Nmda Receptor ◽  
Receptive Field ◽  
Superior Colliculus ◽  
Nmda Receptors ◽  
Field Size ◽  
Stimulus Velocity ◽  
Evolutionary Changes ◽  
Nmda Receptor Blockade ◽  
Nmda Receptor Function ◽  
Injured Region

Neonatal brain injury triggers compensatory processes that can be adaptive or detrimental, but little is known about the mechanisms of compensation or how they might affect the response properties of neurons within the injured region. We have studied this issue in a rodent model. Partial ablation of the hamster superior colliculus (SC) at birth results in a compressed but complete visual field map in the remaining SC and a compensatory conservation of receptive field (RF) size and stimulus velocity and size tuning. The circuit underlying stimulus tuning in this system or its preservation after brain lesions is not known. Our previous work has shown that N-methyl-d-aspartate (NMDA) receptors are necessary for the development and conservation of RF size after partial SC ablation. In this study, we examined whether NMDA receptor function is also necessary for the development and conservation of stimulus velocity and size tuning. We found that velocity and size tuning were unaffected by chronic postnatal blockade of NMDA receptors and the resulting increases in RF size. Thus NMDA receptors in the SC are not necessary for the development of stimulus velocity and size tuning or in the compensatory maintenance of these properties following brain damage. These results suggest that stimulus velocity and size tuning may arise in the retina or from NMDA receptor-independent circuitry intrinsic to SC. The lack of conflict between NMDA receptor activity-dependent and -independent processes may allow conservation of some RF properties while others change during injury-induced or evolutionary changes in afferent/target convergence.

Conservation of receptive-field properties of superior colliculus cells after developmental rearrangements of retinal input

1989 ◽  
Vol 2 (2) ◽  
pp. 121-135 ◽  
Author(s):  
S. L. Pallas ◽  
B. L. Finlay
Keyword(s):  
Receptive Field ◽  
Superior Colliculus ◽  
Ganglion Cells ◽  
Single Cells ◽  
Field Size ◽  
Target Cells ◽  
Topographic Map ◽  
Stimulus Velocity ◽  
Receptive Field Properties ◽  
Single Target

AbstractThe formation of topographic maps requires not only that afferents synapse with the appropriate targets, but that the spatial relationships between the afferents be maintained. During development, in addition to the formation of the topographic map, the connectivity patterns responsible for the receptive-field properties of the target cells are being formed. The extent of interaction between these two processes is unknown. The present study addresses this question by manipulating afferent/target ratios during development, thus altering the topography of the map, and studying the effects of this alteration on the receptive-field properties of single target cells in the adult.Partial unilateral lesions of the superior colliculus (SC) were made in neonatal hamsters. These lesions result in a compression of the retinotopic map onto the remaining collicular fragment. Single cells were recorded from the superficial gray layer of the SC in the adult in response to visual stimuli. Receptive-field properties observed in lesioned animals were compared to those in normal animals and in sham operates.Receptive-field properties were largely unaffected by the change in the topographic map. There was no difference in the receptive-field size of single tectal cells of lesioned and unlesioned animals. Stimulus velocity and stimulus size tuning functions remained the same. This raises the possibility that, rather than the expected increase in convergence of retinal ganglion cells (RGC) onto single collicular cells, single SC cells receive input from ganglion cells representing the same amount of retinal area as in unlesioned animals. The excess ganglion cells created by the partial target removal would then project elsewhere and/or reduce their arbor within the SC. Regardless of the mechanism, it is clear from our results that circuitry in the retinotectal system of the hamster can compensate for conditions of increased afferent availability and thus maintain receptive-field properties.

scholarly journals NMDA Antagonists in the Superior Colliculus Prevent Developmental Plasticity But Not Visual Transmission or Map Compression

2001 ◽  
Vol 86 (3) ◽  
pp. 1179-1194 ◽  
Author(s):  
L. Huang ◽  
S. L. Pallas
Keyword(s):  
Receptive Field ◽  
Superior Colliculus ◽  
Nmda Receptors ◽  
Developmental Plasticity ◽  
Receptive Fields ◽  
Visual Space ◽  
Nervous System Development ◽  
Field Size ◽  
Absolute Amount ◽  
General Importance

Partial ablation of the superior colliculus (SC) at birth in hamsters compresses the retinocollicular map, increasing the amount of visual field represented at each SC location. Receptive field sizes of single SC neurons are maintained, however, preserving receptive field properties in the prelesion condition. The mechanism that allows single SC neurons to restrict the number of convergent retinal inputs and thus compensate for induced brain damage is unknown. In this study, we examined the role of N-methyl-d-aspartate (NMDA) receptors in controlling retinocollicular convergence. We found that chronic 2-amino-5-phosphonovaleric acid (APV) blockade of NMDA receptors from birth in normal hamsters resulted in enlarged single-unit receptive fields in SC neurons from normal maps and further enlargement in lesioned animals with compressed maps. The effect was linearly related to lesion size. These results suggest that NMDA receptors are necessary to control afferent/target convergence in the normal SC and to compensate for excess retinal afferents in lesioned animals. Despite the alteration in receptive field size in the APV-treated animals, a complete visual map was present in both normal and lesioned hamsters. Visual responsiveness in the treated SC was normal; thus the loss of compensatory plasticity was not due to reduced visual responsiveness. Our results argue that NMDA receptors are essential for map refinement, construction of receptive fields, and compensation for damage but not overall map compression. The results are consistent with a role for the NMDA receptor as a coincidence detector with a threshold, providing visual neurons with the ability to calculate the amount of visual space represented by competing retinal inputs through the absolute amount of coincidence in their firing patterns. This mechanism of population matching is likely to be of general importance during nervous system development.

Intrathecal blockade of both NMDA and non-NMDA receptors attenuates the exercise pressor reflex in cats

1996 ◽  
Vol 80 (1) ◽  
pp. 315-322 ◽  
Author(s):  
C. M. Adreani ◽  
J. M. Hill ◽  
M. P. Kaufman
Keyword(s):  
Spinal Cord ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Initial Phase ◽  
Intrathecal Injection ◽  
Secondary Phase ◽  
Receptor Blockade ◽  
Lumbosacral Spinal Cord ◽  
Ventilatory Responses ◽  
Nmda Receptor Blockade

In decerebrate unanesthetized cats we tested the hypothesis that glutamatergic-receptor blockade in the lumbosacral spinal cord attenuated the reflex increases in mean arterial pressure, inspired minute ventilation, and renal sympathetic nerve activity (RSNA) evoked by static contraction of the triceps surae muscles. Blockade of N-methyl-D-aspartate (NMDA) receptors by intrathecal injection of DL-2-amino-5-phosphonovaleric acid had no effect on the initial phase of the pressor, ventilatory, and RSNA responses to contraction but did attenuate the secondary phase of these responses. Subsequent blockade of non-NMDA receptors in the lumbosacral spinal cord by intrathecal injection of 6-cyano-7-nitroquinoxaline-2,3-dione attenuated both the initial phase of the pressor, RSNA, and ventilatory responses to contraction and the secondary phase of these responses. In addition, NMDA-receptor blockade had no effect on the pressor or RSNA responses to tendon stretch, whereas non-NMDA-receptor blockade abolished these responses. We confirmed that our results were not related to the order of the antagonists injected by performing a series of experiments in which a non-NMDA-receptor antagonist was injected first. Our findings suggest that non-NMDA receptors mediate the spinal transmission of the initial and secondary phases of the pressor, RSNA, and ventilatory responses to contraction and tendon stretch. Therefore, non-NMDA receptors in the dorsal horn appear to be involved in the spinal processing of input from mechanoreceptors and metaboreceptors. Our findings also suggest that NMDA receptors mediate the spinal transmission of the secondary phase of the pressor, RSNA, and ventilatory responses to contraction but do not mediate the spinal transmission of the responses to tendon stretch. Therefore, NMDA receptors in the dorsal horn appear to be involved in the spinal processing of input from metaboreceptors.

Importance of NMDA receptors for multimodal integration in the deep layers of the cat superior colliculus

1996 ◽  
Vol 75 (2) ◽  
pp. 920-930 ◽  
Author(s):  
K. E. Binns ◽  
T. E. Salt
Keyword(s):  
Nmda Receptor ◽  
Superior Colliculus ◽  
Nmda Receptors ◽  
Nmda Receptor Antagonist ◽  
Multimodal Integration ◽  
Nonlinear Properties ◽  
Somatosensory Information ◽  
Deep Layers ◽  
Sensory Responses ◽  
Single Modality

1. Many sensory events contain multimodal information, yet most sensory nuclei are devoted to the analysis of single-modality information. In the deep superior colliculus (DSC), visual, auditory, and somatosensory information converges on individual multimodal neurons. The responses of multimodal neurons are determined by the temporal and spatial correspondence properties of the converging inputs such that stimuli arising from the same event elicit a facilitated multimodal response. 2. N-methyl-D-aspartate (NMDA) receptors may underlie the detection of spatial and temporal coincidence and could be involved in the generation of multimodal facilitatory responses because of the nonlinear properties of NMDA-receptor-mediated events. To assess the role of NMDA receptors in multimodal integration, we made extracellular recordings from single multisensory neurons in the DSC of the cat. 3. The responses to visual, auditory, and somatosensory stimuli alone and to multimodal combinations of stimuli were challenged with iontophoretically applied D-2-amino-5-phosphonovalerate (AP5), an NMDA receptor antagonist. All responses to visual stimuli presented alone (n = 9) were greatly reduced. Somatosensory responses (n = 25) were usually decreased. In contrast, the responses to auditory stimulation were decreased (n = 9), unaffected (n = 3), or enhanced (n = 5). 4. Responses to multimodal stimulus presentations were consistently reduced during iontophoretic application of AP5, irrespective of the modalities that made up the stimulus. The reductions of multimodal responses were significantly greater than the sum of the reductions of responses to single-modality stimuli. 5. The data suggest that for unimodal stimuli, the importance of NMDA receptors in synaptic transmission of sensory responses in DSC may be dependent on the stimulus modality. Furthermore, NMDA receptors are of major importance in the integration of input from different modalities for the generation of multimodal responses.

Effects of visual cortical lesions on receptive-field properties of single units in superior colliculus of the rabbit

1982 ◽  
Vol 47 (2) ◽  
pp. 272-286 ◽  
Author(s):  
J. Graham ◽  
N. Berman ◽  
E. H. Murphy
Keyword(s):  
Receptive Field ◽  
Superior Colliculus ◽  
Receptive Fields ◽  
Simultaneous Presentation ◽  
Single Units ◽  
Stimulus Velocity ◽  
Response Characteristics ◽  
Transient Nature ◽  
Receptive Field Properties ◽  
Stroboscopic Illumination

1. One hundred seventy-nine single units were studied in the superior colliculus of seven Dutch-belted rabbits following ablation of the ipsilateral visual cortex. The response characteristics of these units were compared with those of 284 single units recorded from the superior colliculus of 20 intact animals. 2. In both the upper and lower parts of the stratum griseum superficiale and in the stratum griseum intermediate, there were smaller proportions of direction-selective visual units in the decorticated animals than in normal ones. 3. In the upper stratum griseum superficiale, a larger proportion of units responded to stroboscopic illumination in the decorticated animals than in normal ones. Also, in the decorticated animals, there was a larger proportion of units whose responses to a small moving stimulus were inhibited by the simultaneous presentation of stroboscopic illumination. 4. In both the upper and lower parts of the stratum griseum superficiale, a larger proportion of visual units responded well to stationary stimuli and a smaller proportion of visual units showed habituation in decorticated animals compared to normal ones. 5. In the lower stratum griseum superficiale, the receptive fields of units were larger and were more elongated in the anterior-posterior dimension in the decorticated animals than in normal ones. 6. In the two preparations, units did not differ in responsiveness or spontaneous activity; and visual units did not differ in the sustained or transient nature of their responses, the selectivity for light or dark stimuli, the selectivity for onset or offset of the stimuli, or the selectivity for stimulus velocity. 7. This study provides evidence for the importance of the visual corticotectal projection in the elaboration of the visual receptive-field properties of units in the superior colliculus of the rabbit. In addition, this study shows that the subdivisions of the superior colliculus are differentially affected by the loss of the visual corticotectal projection.

scholarly journals Dysregulation of erythropoiesis and altered erythroblastic NMDA receptor-mediated calcium influx in Lrfn2-deficient mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245624
Author(s):  
Ryuta Maekawa ◽  
Hideki Muto ◽  
Minoru Hatayama ◽  
Jun Aruga
Keyword(s):  
Bone Marrow ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Bone Marrow Cells ◽  
Calcium Influx ◽  
Marrow Cell ◽  
Nmda Receptor Antagonist ◽  
Receptor Expression ◽  
Nmda Receptor Function ◽  
Marrow Cells

LRFN2 encodes a synaptic adhesion-like molecule that physically interacts with N-methyl-D-aspartate (NMDA) receptor 1 and its scaffold proteins. Previous studies in humans and mice have demonstrated its genetic association with neurodevelopmental disorders such as learning deficiency and autism. In this study, we showed that Lrfn2-deficient (KO) mice exhibit abnormalities of erythropoietic systems due to altered NMDA receptor function. In mature Lrfn2 KO male mice, peripheral blood tests showed multilineage abnormalities, including normocytic erythrocythemia, and reduced platelet volume. Colony forming unit assay using bone marrow cells revealed decreases in the counts of erythrocyte progenitors (CFU-E) as well as granulocytes and monocyte progenitors (CFU-GM). Whole bone marrow cell staining showed that serum erythropoietin (EPO) level was decreased and EPO receptor-like immunoreactivity was increased. Flow cytometry analysis of bone marrow cells revealed increased early erythroblast count and increased transferrin receptor expression in late erythroblasts. Further, we found that late erythroblasts in Lrfn2 KO exhibited defective NMDA receptor-mediated calcium influx, which was inhibited by the NMDA receptor antagonist MK801. These results indicate that Lrfn2 has biphasic roles in hematopoiesis and is associated with the functional integrity of NMDA receptors in hematopoietic cells. Furthermore, taken together with previous studies that showed the involvement of NMDA receptors in hematopoiesis, the results of this study indicate that Lrfn2 may regulate erythropoiesis through its regulatory activity on NMDA receptors.

Suppression of NMDA Receptor Function Using Antisense DNA Blocks Ocular Dominance Plasticity While Preserving Visual Responses

1998 ◽  
Vol 80 (3) ◽  
pp. 1021-1032 ◽  
Author(s):  
Elizabeth B. Roberts ◽  
M. Alex Meredith ◽  
Ary S. Ramoa
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Ocular Dominance ◽  
Receptor Function ◽  
Visual Responses ◽  
Ocular Dominance Plasticity ◽  
Cortical Cells ◽  
Nmda Receptor Function ◽  
Sensory Responses

Roberts, Elizabeth B., M. Alex Meredith, and Ary S. Ramoa. Suppression of NMDA receptor function using antisense DNA blocks ocular dominance plasticity while preserving visual responses. J. Neurophysiol. 80: 1021–1032, 1998. 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 α-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.

Effects of cooling somatosensory cortex on response properties of tactile cells in the superior colliculus

1986 ◽  
Vol 55 (6) ◽  
pp. 1352-1368 ◽  
Author(s):  
H. R. Clemo ◽  
B. E. Stein
Keyword(s):  
Receptive Field ◽  
Superior Colliculus ◽  
Somatosensory Cortex ◽  
Critical Role ◽  
Receptive Fields ◽  
Field Size ◽  
Specific Cell ◽  
Anterior Ectosylvian Sulcus ◽  
Cortical Cooling ◽  
Cortical Regions

The corticotectal influences of somatosensory cortex were investigated by using reversible deactivation of cortex by cooling. More than half of the somatosensory superior colliculus (SC) cells studied exhibited a response depression (often not apparent qualitatively) or an elimination of responses to somatosensory stimuli during the period in which cortex was rendered inactive. Responses were restored to their initial levels by cortical rewarming. Hyperresponsiveness was never observed as a consequence of cortical cooling. Susceptibility to cooling-induced depression was not invariably linked to a specific cell type, location in the SC, or receptive-field size. Yet cells that had small receptive fields and were activated by hair displacement had the highest probability of being affected by this procedure. In some cells a contraction of the receptive field was induced by cortical cooling. This observation is consistent with previous experiments that showed that SC somatosensory receptive fields are constructed by the convergence of ascending and descending inputs and indicates that the responsiveness of specific receptive-field regions may depend on the functional integrity of cortex. Two cortical regions were found to produce cooling-induced effects in somatosensory SC cells: 1) SIV (and para-SIV), located in the anterior ectosylvian sulcus, and 2) the cortex within the rostral suprasylvian sulcus. These results indicate that somatosensory cortex, like visual cortex, plays a critical role in modulating the responses of SC cells. Apparently, the ability of both somatosensory and visual SC cells to code the presence of peripheral stimuli depends largely on the functional influences of their respective cortices. However, in contrast to previous observations on visual corticotectal influences, no specific receptive-field properties could be shown to be impressed on SC cells by somatosensory cortex.

scholarly journals Structure, Function, and Pharmacology of NMDA Receptor Channels

2014 ◽  
pp. S191-S203 ◽  
Author(s):  
V. VYKLICKY ◽  
M. KORINEK ◽  
T. SMEJKALOVA ◽  
A. BALIK ◽  
B. KRAUSOVA ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Synaptic Transmission ◽  
Nmda Receptors ◽  
Neural Plasticity ◽  
Receptor Activation ◽  
Neuroprotective Drugs ◽  
Receptor Inhibition ◽  
Nmda Receptor Function ◽  
The One ◽  
Nmda Receptor Activation

NMDA receptors have received much attention over the last few decades, due to their role in many types of neural plasticity on the one hand, and their involvement in excitotoxicity on the other hand. There is great interest in developing clinically relevant NMDA receptor antagonists that would block excitotoxic NMDA receptor activation, without interfering with NMDA receptor function needed for normal synaptic transmission and plasticity. This review summarizes current understanding of the structure of NMDA receptors and the mechanisms of NMDA receptor activation and modulation, with special attention given to data describing the properties of various types of NMDA receptor inhibition. Our recent analyses point to certain neurosteroids as NMDA receptor inhibitors with desirable properties. Specifically, these compounds show use-dependent but voltage-independent block, that is predicted to preferentially target excessive tonic NMDA receptor activation. Importantly, neurosteroids are also characterized by use-independent unblock, compatible with minimal disruption of normal synaptic transmission. Thus, neurosteroids are a promising class of NMDA receptor modulators that may lead to the development of neuroprotective drugs with optimal therapeutic profiles.

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