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PubMed1997

Immunization of non-human primates with DNA vaccines.

The pre-clinical efficacy of DNA vaccines has been demonstrated in a number of animal models, but more limited data exist regarding their immunogenicity in non-human primates. The studies described below demonstrate that DNA vaccines in reasonable dosages encoding a variety of viral proteins could result in the generation of antibodies, neutralizing antibodies, or cytotoxic T lymphocytes in primates. Furthermore, these responses could be boosted by repeat administration of the DNA vaccine. In an effort to assess the safety of such vaccines sera from primates was shown to lack anti-DNA antibodies.

Animals↗
PubMed2000

African green monkeys provide a useful nonhuman primate model for the study of human parainfluenza virus types-1, -2, and -3 infection.

Human parainfluenza virus (HPIV) types-1, -2, and -3 are significant causes of both upper and lower respiratory tract disease in infants and children. Although there are two live attenuated vaccines for the prevention of HPIV-3 disease in phase 1 clinical trials, vaccines are not currently available for prevention of HPIV-1 or -2 disease. Our laboratory is developing candidate vaccines for the prevention of HPIV-1, -2, and -3 disease, and a suitable nonhuman primate model is needed for evaluation of these vaccine candidates prior to administration to humans. We evaluated the replication of HPIV-1 and -2 in six different species of nonhuman primates and found both viruses to replicate most efficiently in African green monkeys and chimpanzees. We then compared the replication of HPIV-3 in African green monkeys to that in rhesus macaques, which we have used previously, and found that HPIV-3 replicated to higher titer in African green monkeys. In summary, African green monkeys provide a very useful nonhuman primate for the evaluation of HPIV-1, -2, and -3 vaccine candidates, especially for the evaluation of various combinations of these PIV vaccines and for vaccine strategies that employ sequential immunization.

Animals↗
PubMed1997

Lack of ovarian steroid hormone regulation of norepinephrine transporter mRNA expression in the non-human primate locus coeruleus.

Decreases in ovarian steroids can negatively affect mood, and drugs which block the norepinephrine transporter (NET) or the serotonin transporter (SERT) alleviate depression. However, the respective contribution of the noradrenergic and serotonergic systems may vary depending upon the etiology of the depression. We previously demonstrated that E and P alter gene expression for tryptophan hydroxylase (TPH) and for the serotonin reuptake transporter (SERT) in raphe neurons of the rhesus monkey. In this study, we questioned whether the noradrenergic system contributes to depression related to the reproductive function in women, using a non-human primate model of the menstrual cycle. The effect of estrogen (E) or E plus progesterone (P) on the expression of the NET gene in the locus coeruleus (LC) was examined with in situ hybridization for NET mRNA. In addition, we questioned whether the neurons of the LC contain nuclear E or P receptors (ER/PR). Hence, immunocytochemistry for ER and PR were performed on adjacent sections. Treatment groups consisted of monkeys (n = 4 per treatment) which were ovariectomized/hysterectomized (spayed), E-treated (28 days) and E+P-treated (14 days E, +14 days E+P). Expression of mRNA for NET was unchanged at any level of the LC due to steroid treatment (p > .05). Neither ER nor PR were detected in the LC of any treatment group. Therefore, E and P in a treatment paradigm which mimics the menstrual cycle do not directly regulate NET mRNA expression in the non-human primate LC. In addition, the noradrenergic neurons of the primate LC lack nuclear receptors for ovarian steroids. These data suggest that the noradrenergic system may not contribute significantly to depression related to changes in ovarian hormones.

Animals↗
PubMed2001

Tissue printing of astroglial interlaminar processes from human and non-human primate cerebral cortex.

Astroglial interlaminar processes are unique features of the cerebral cortex of adult primates, including man. The functional role of these processes in the primate cerebral cortex is largely unknown. The development and standardization of procedures that could maximize the utilization of primate brain samples is required for the experimental analysis of the individual and collective dynamic properties of interlaminar glial processes. With this aim and in order to assess the relative stability of these glial processes in ex vivo conditions, "tissue printing" procedures were applied. "Tissue printing" allows for the acute transfer of cellular elements from fresh tissue onto an artificial substrate. Human, monkey (Cebus apella), and rat brain samples were subjected to "tissue printing" procedures followed by cell culture and immunohistochemistry. For the purpose of comparing the efficiency of this procedure on the transfer of other long glial processes, "tissue prints" of radial glial processes from neonatal rats and of Bergmann glia from cerebellar samples of adult rats were included. Nitrocellulose (with and without added fibronectin or laminin) produced the best attachment results. Interlaminar processes were not modified following 24-h incubation in a cell culture medium, with the addition of agents known to modify astroglial morphotypes in vitro (cyclic adenosine monophosphate, 40 mM K(+), or fetal calf serum). It is concluded that glia with interlaminar processes can be detached from fresh tissue using "tissue printing" procedures, can be maintained for at least 24 h in standard culture conditions, and showed a stable morphological phenotype.

Animals↗
PubMedDate not supplied

Comparative aspects of the olfactory portion of the entorhinal cortex and its projection to the hippocampus in rodents, nonhuman primates, and the human brain.

The entorhinal cortex is a component of the hippocampal formation characterized by its projection to the dentate gyrus. Cortical input is relayed to the hippocampus through the entorhinal cortex. The entorhinal cortex can be recognized best in mammals, and it reaches its maximal importance in both human and nonhuman primates. In primates, but not in rodents, the olfactory projection from the olfactory bulb is the only direct sensory projection reaching the entorhinal cortex, where it defines a rostromedial subfield (olfactory subfield of the entorhinal cortex, EO). In this communication, we consider some comparative aspects of this projection in rodents, nonhuman primates, and human brains, in relation to the forward projection to the hippocampus. We base our analysis on the following three considerations: (1) Topology: Topologically, the entorhinal cortex lies medial to the rhinal fissure, well developed in all mammals except in humans. EO maintains the same topological relationship to the rhinal fissure in the three mammalian orders. (2) Cytoarchitecture: The rostromedial portion shows poorer lamination compared with caudomedial portions of the entorhinal cortex in the three mammalian orders examined. (3) Connectivity: In rodents, the olfactory projection covers the whole extent of the entorhinal cortex, whereas it decreases substantially in macaques, where it roughly covers 15% of the entorhinal cortex. The human EO as defined by topological and cytoarchitectonic criteria may be even less than in macaques. Interestingly, good evidence exists that all of these mammalian orders maintain the same topographical scheme of projection to the rostral end of the hippocampus.

Animals↗
PubMed2000

Structural variations of the VWA locus in humans and comparison with non-human primates.

The HUMVWA locus was examined in 160 samples from the Japanese population. A total of 142 fragments were sequenced, and the counterpart sequences were also determined in non-human primates. In humans, 10 different alleles were found; they could be grouped into seven allelic classes based on the total number of repeats. No variation was observed in the alleles 17, 18 and 19, which showed consensus sequence structures and in the allele 14, which showed a different structure. New variation was found in alleles 15, 16, and 20, which had differences occurred in a basic (TCTA)(TCTG)(n) repeat in the 5' side. The counterpart fragments were successfully amplified in three species (chimpanzees, gorilla, and orangutan) out of four kinds of anthropoids, three species (rhesus macaques, Japanese macaques, and green monkey) out of four kinds of old world monkeys, but not in one species of either new world monkey or prosimian. The sizes of the fragments distributed from 92 to 180 bp in non-human primates and showed allelic size differences in four species. The sequence of the 5' flanking region followed by primer sequences in humans and anthropoids, which consisted of 19 bp, was identical in all, but differed from that in old world monkeys. The basic repeat motifs of humans and anthropoids consisted of TCTA, TCTG, and TCCA but that of old world monkeys consisted of TCTG, TCCG and TCCA The structures of humans and anthropoids were essentially similar, but with characteristic difference in each species. Differences in the allelic structures of old world monkeys were complex. Seven different alleles were observed in two rhesus and two Japanese macaques and one type of allele was observed in two green monkeys. Duplication of more than two repeat units of 4 bp was found in an allele of an old world monkey. These data illuminate interesting features of mutational changes in STRs during the long generations and also some insight into evolutional aspects of primates.

Animals↗
PubMed1998

Strategies for tolerance induction in nonhuman primates.

Organ transplants in nonhuman primates provide a model which closely simulates the biological conditions of human organ transplantation, due to similarities between human and primate MHC (class I and II) structure and expression. Several strategies for tolerance induction have been developed in nonhuman primate models. These include targeting the T cell receptor or costimulatory molecules and the generation of mixed chimerism. Tolerance can be reliably induced in several such models, although none with 100% success.

Animals↗
PubMed1998

Removal of primate xenoreactive natural antibodies by extracorporeal perfusion of pig kidneys and livers.

Organ perfusion is one of the possible strategies to attenuate rejection of discordant xenografts by reducing the levels of the recipient's xenoreactive natural antibodies (XNA). Its efficacy in terms of XNA removal was studied in models of primate blood or plasma perfusion through porcine kidneys or livers, with special attention to haematological consequences and potential side-effects. We first perfused the blood of rhesus monkeys through pig kidneys and livers, and demonstrated that the perfusion of a pig liver resulted in higher XNA adsorption (72 +/- 13%) than the perfusion of a pig kidney (51 +/- 25%). However, when we normalized for the weight of the perfused organs and for levels of natural antibodies in individual monkeys, livers adsorbed less antibody (1.4 +/- 0.9 U antibody/g) than kidneys (7.2 +/- 7 U antibody/g). Histological signs of rejection were observed in perfused kidneys, but not in perfused livers. A major drawback of the perfusion of blood through livers was a considerable decrease in the primates' haemoglobin and platelet levels. To avoid this, we developed a plasma liver perfusion device. This method allowed a significant improvement in the haemodynamic state of primates and was particularly effective in preventing anaemia. Moreover, plasma liver perfusion was as effective as blood liver perfusion to remove natural antibodies and, resulted in a marked decrease in their functional activity as assessed by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). The level of other plasma proteins was not significantly affected, apart from a dilution effect. After xenoperfusion a strong antibody response was evidenced by ELISA, CDC and ADCC between days 7 and 14 and then decreased progressively. We conclude that the separation of blood to allow the perfusion of plasma through a pig organ is safer than the perfusion of unseparated blood and is associated with efficient natural antibody removal. However, organ perfusion is limited by a rebound in antibody levels after a few days, and thus will have to be associated with anti-B cell immunosuppressive therapy for long-term or repeated applications.

Animals↗
PubMed2003

Genetic manipulation of primate embryonic and hematopoietic stem cells with simian lentivirus vectors.

During the past several years, many articles have described how human embryonic stem (ES) cells and adult hematopoietic stem cells (HSCs) can differentiate into cardiac muscle, blood vessels, and various other types of cells. The articles raised the expectation that these stem cells may become useful for the treatment of a variety of diseases, including cardiovascular diseases. Genetic manipulation of ES cells and HSCs would be important for such future applications of the cells. Until now, retroviral vectors have been used primarily for stable expression of transgenes in murine ES cells and HSCs. Because murine models may not predict reliably the biology of ES cells and HSCs in humans, we have utilized primate ES cells and HSCs as targets of gene transfer. We have shown that primate ES cells and HSCs can be transduced efficiently with lentiviral vectors derived from the simian immunodeficiency virus, and that the high transgene expression persists without transcriptional silencing. This highly efficient gene transfer method allows for safe and faithful gene delivery to primate ES cells and HSCs to test potential research and therapeutic applications.

Animals↗
PubMed2000

Monitoring pig-to-primate cardiac xenografts with live Internet images of recipients and xenograft telemetric signals: histologic and immunohistochemical correlations.

BACKGROUND: Monitoring pig-to-primate cardiac xenografts is often difficult in awake and uncooperative primates. We investigated the possibility of monitoring xenotransplantation through Internet broadcasting of (1) continuous video images of transplant recipients and (2) xenograft telemetric signals detected by an implanted device. The telemetric readings were later compared with histology and immunohistochemistry for signs of rejection. METHODS: Heterotopic baboon-to-baboon (n = 2) and transgenic pig (human complement regulatory proteins CD59/DAF, n = 3; MCP, n = 1)-to-baboon transplants were performed with serial biopsies for hematoxylin-and-eosin staining and immunohistochemical detection of immunoglobulin M (IgM) and complement membrane attack complex (MAC) deposition. Baboon recipients were continuously monitored with a QuickCamPro digital camera, whereas grafts were monitored with a Data Science International implantable telemetric system. Video images and telemetric signals were broadcast over the Internet through a laptop computer. RESULTS: Baboon allografts remained healthy until explant on Day 14, whereas pig xenografts were rejected on Day 5, 6, 7, and 11. Telemetry of allografts and xenografts documented regular rhythm with an average heart rate of 80 to 120, but xenografts developed bradycardia and widened/dampened QRS complexes 24 to 48 hours before graft loss. Continuous video monitoring of recipient activities was vital in differentiating between graft arrhythmias and telemetric artifacts. Allograft biopsies showed little cellular infiltrate, whereas xenograft biopsies showed increasing IgM and MAC deposition, with extensive thrombi and myocardial damage 24 hours before cessation of cardiac activities. CONCLUSIONS: Combined video surveillance of recipient activities and graft telemetric signals is a useful method to continuously monitor abdominal cardiac grafts in large, uncooperative, awake primates. QRS-complex widening associated with progressive bradycardia correlated with histologic and immunohistochemical evidence of xenograft rejection.

Animals↗
PubMed2003

In vivo evaluation of the novel calcineurin inhibitor ISATX247 in non-human primates.

BACKGROUND: ISA(TX)247 is a novel calcineurin inhibitor that has shown more potency than cyclosporine in vitro. This is the first in vivo study of the effects of ISA(TX)247 on lymphocyte functions in non-human primates. METHODS: Groups of cynomolgus monkeys were treated orally twice daily for 7 days, each dose consisting of 25 mg/kg cyclosporine (n = 5), 25 mg/kg ISA(TX)247 (n = 6) or 50 mg/kg ISA(TX)247 (n = 6). Levels of cyclosporine and ISA(TX)247 in whole blood were measured by liquid chromatography/mass spectrometry. After mitogen stimulation, lymphocyte proliferation was assessed by tritium-labeled thymidine incorporation and by flow cytometry (expression of proliferating cell nuclear antigen in cells in S/G(2)M phase). Flow cytometry was also used to assess production of intracellular cytokines by T cells (interleukin-2, interferon-gamma, tumor necrosis factor-alpha) and expression of T-cell surface activation antigens (CD25, CD71, CD11a, CD95, CD154). RESULTS: Trough (C(14 hr)) and peak (C(3 hr)) drug levels, as well as area under the concentration-time curve, were significantly higher for cyclosporine than ISA(TX)247 (370 ng/ml vs 70 ng/ml, 877 ng/ml vs 303 ng/ml and 6,262 ng. h/ml vs 1,979 ng. h/ml, respectively). On Day 7 at C(14 hr), lymphocyte proliferation had been suppressed by approximately 50% in all groups compared with proliferation before treatment. Three hours after dosing, lymphocyte proliferation was inhibited significantly more by ISA(TX)247 (approximately 80%, with no differences between the two ISA(TX)247 dose levels) than by cyclosporine (65% inhibition). Similar differences between the immunosuppressive effects of ISA(TX)247 and cyclosporine were found for inhibition of expression of T-cell surface activation antigens. Despite lower ISA(TX)247 exposures compared with cyclosporine, the cyclosporine treatment only rarely suppressed cytokine production more than treatment with ISA(TX)247. CONCLUSIONS: In non-human primates, ISA(TX)247 produces a greater or similar inhibition of lymphocyte proliferation, expression of T-cell activation surface antigens, and cytokine production when compared with cyclosporine, despite ISA(TX)247's lower blood levels and total exposure. We conclude that ISA(TX)247 suppresses diverse T-cell functions more potently than cyclosporine in non-human primates in vivo.

Animals↗
PubMed2003

Mapping of brain function after MPTP-induced neurotoxicity in a primate Parkinson's disease model.

Neurophysiological studies of the brain in normal and Parkinson's disease (PD) patients have indicated intricate connections for basal ganglia-induced control of signaling into the motor cortex. To investigate if similar mechanisms are controlling function in the primate brain (Macaca fascicularis) after MPTP-induced neurotoxicity, we conducted PET studies of cerebral blood flow, oxygen and glucose metabolism, dopamine transporter, and D2 receptor function. Our observations after MPTP-induced dopamine terminal degeneration of the caudate and putamen revealed increased blood flow (15%) in the globus pallidus (GP), while blood flow was moderately decreased (15-25%) in the caudate, putamen, and thalamus and 40 % in the primary motor cortex (PMC). Oxygen extraction fraction was moderately increased (10-20%) in other brain areas but the thalamus, where no change was observable. Oxygen metabolism was increased in the GP and SMA (supplementary motor area including premotor cortex, Fig. 3) by a range of 20-40% and decreased in the putamen and caudate and in the PMC. Glucose metabolism was decreased in the caudate, putamen, thalamus, and PMC (range 35-50%) and enhanced in the GP by 15%. No change was observed in the SMA. In the parkinsonian primate, [(11)C]CFT (2beta-carbomethoxy-3beta-(4-fluorophenyltropane) dopamine transporter binding was significantly decreased in the putamen and caudate (range 60-65%). [(11)C]Raclopride binding of dopamine D(2) receptors did not show any significant changes. These experimental results obtained in primate studies of striato-thalamo-cortico circuitry show a similar trend as hypothetized in Parkinson's disease-type degeneration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMedDate not supplied

Tachycardia-induced primate model of heart failure in cardiovascular drug discovery.

Congestive heart failure (CHF) is a complex, multifactoral disease involving genetic and environmental factors that represents a large unmet medical need. There are currently many animal models of CHF that have provided some insight into the etiology of this disease. However, due to the complex interactions of environmental and genetic components of this disease most animal models are somewhat limited. Nonhuman primates offer a unique opportunity to investigate the genetic aspects of this complex disease due to their close genetic and phenotypic similarity to humans. Here we describe a novel tachycardia-induced primate model of CHF characterized by depressed global function that progresses to a symptomatic stage consistent with clinical data. No animal model, including this one, can exactly mimic the clinical pathophysiology of CHF. However, this tachycardia-induced primate model of CHF has similarities to the dynamic state of CHF in humans and affords the opportunity to evaluate changes in gene expression using genomic and proteomic technologies throughout the progression of the disease.

Animals↗
PubMed1998

Influence of daylength on metabolic rate and daily water loss in the male prosimian primate Microcebus murinus.

In its natural habitat, Microcebus murinus, a small malagasy prosimian primate, is exposed to seasonal shortage of water and resources. During the winter dry season, animals enter a pronounced fattening period with concurrent decrease in behavioural/physiological activities, whereas the breeding season is restricted to the rainy summer months. To determine the role of daylength on metabolic rate and water loss in this nocturnal primate, we measured body mass, oxygen consumption at 25 degrees C (RMR), circadian water loss through urine output (UO) and evaporation (EWL) in eight males exposed to either short days (8L:16D SD) or long days (14L:10D LD), under controlled captive conditions. Exposure to SD led to a ponderal increase (maximal body mass: 125 +/- 4 g, N = 8), and to significant changes in RMR and water loss, both reaching lowest values after 3 months under SD (0.84 +/- 0.04 ml O2 h-1 g-1 and 38 +/- 0.3 mg H2O g-1 day-1, respectively). Following exposure to LD, body mass decreased to 77 +/- 3 g (N = 8), whereas both RMR and water loss, mainly through EWL, significantly increased (P < 0.001), the highest value occurring after 2 months (1.51 +/- 0.08 ml O2 h-1 g-1 and 87 +/- 7 mgH2O g-1 day-1, respectively). Moreover, independent of daylength, circadian changes in EWL were characterized by significantly reduced values during the diurnal rest. The results demonstrate that daylength variations affect the physiology of this tropical primate, allowing anticipatory adaptation to seasonal environmental constraints.

Animals↗
PubMed2000

Delivering drugs, via microdialysis, into the environment of extracellularly recorded hippocampal neurons in behaving primates.

Hippocampal neurons in primates have been extensively studied with electrophysiological and neuroanatomical methods. Much less effort has been devoted to examining these cells with contemporary pharmacological techniques. Therefore, we modified a recently developed integrative technique (N. Ludvig, P.E. Potter, S.E. Fox, Simultaneous single-cell recording and microdialysis within the same brain site in freely behaving rats: a novel neurobiological method, J. Neurosci. Methods 55 (1994) 31-40 [9] ) for cellular neuropharmacological studies in behaving monkeys. A driveable microelectrode-microdialysis probe guide assembly was implanted stereotaxically into the left hippocampus of squirrel monkeys (Saimiri sciureus) under isoflurane anesthesia. The assembly was covered with a protective cap. After 3 weeks of postsurgical recovery and behavioral training, the experimental subject was seated in a primate chair. For 4-5 h, single-cell recording and microdialysis were simultaneously performed in the hippocampal implantation site. The technique allowed the recording of both complex-spike cells and fast-firing neurons without the use of head restraint. The control microdialysis solution, artificial cerebrospinal fluid (ACSF), was replaced with either 1 M ethanol or 500 microM N-methyl-D-aspartate (NMDA) for 10-30 min intervals. The ethanol perfusions principally suppressed the firing of the neurons in the dialysis area. The NMDA perfusions initially increased the firing of local neurons, then caused electrical silence. These drug delivery/cell recording sessions were performed with 1-4 day intersession intervals over a 1-month period. The described method provides a tool to elaborate the pharmacology of primate hippocampal neurons during behavior and without the confounding effects of systemic drug administrations.

Animals↗
PubMed2003

Generation of protective immunity by inactivated recombinant staphylococcal enterotoxin B vaccine in nonhuman primates and identification of correlates of immunity.

At this time there are no vaccines or therapeutics to protect against staphylococcal enterotoxin B (SEB) exposure. Here, we report vaccine efficacy of an attenuated SEB in a nonhuman primate model following lethal aerosol challenge and identify several biomarkers of protective immunity. Initial in vitro results indicated that the mutation of key amino acid residues in the major histocompatibility complex (MHC) class II binding sites of SEB produced a nontoxic form of SEB, which had little to no detectable binding to MHC class II molecules, and lacked T-cell stimulatory activities. When examined in a mouse model, we found that the attenuated SEB retained antigenic structures and elicited protective immune responses against wild-type SEB challenge. Subsequently, a vaccine regimen against SEB in a nonhuman primate model was partially optimized, and investigations of immune biomarkers as indicators of protection were performed. SEB-naïve rhesus monkeys were vaccinated two or three times with 5 or 20 microg of the attenuated SEB and challenged by aerosol with wild-type SEB toxin. Unlike exposure to the native toxin, the vaccine did not trigger the release of inflammatory cytokines (TNF alpha, IL6, or IFN gamma). All rhesus monkeys that developed anti-SEB serum titers > or = 10(4) and elicited high levels of neutralizing antibody survived the aerosol challenge. These findings suggest that the attenuated SEB is fully protective against aerosolized toxin when administered to unprimed subjects. Moreover, experiments presented in this study identified various biomarkers that showed substantial promise as correlates of immunity and surrogate endpoints for assessing in vivo biological responses in primates, and possibly in humans, to vaccines against SEs.

Animals↗
PubMedDate not supplied

Center/surround relationships of magnocellular, parvocellular, and koniocellular relay cells in primate lateral geniculate nucleus.

As in other primates, the lateral geniculate nucleus (LGN) of the prosimian primate, bush baby (Galago crassicaudatus), contains three morphologically and physiologically distinct cell classes [magnocellular (M), parvocellular (P), and koniocellular (K)] (Norton & Casagrande, 1982; Casagrande & Norton, 1991). The present study examined quantitatively the center/surround relationships of cells in all three classes. Estimates of receptive-field center size (Rc) and sensitivity (Kc) and of surround size (Rs) and sensitivity (Ks) were obtained from 47 LGN relay cells by fitting a difference of Gaussians function to contrast-sensitivity data. For M and P cells, center size (Rc) increases with eccentricity but is about two times larger for M than for P cells at a given eccentricity. Surround size (Rs) increases with eccentricity for P but not for M or K cells. The center sensitivity (Kc) is inversely related to center size (Rc) and surround sensitivity (Ks) is inversely related to surround size (Rs) for cells in all classes, a result consistent with the sensitivity regulation that is produced by light adaptation. High spatial-frequency cutoff (acuity) is inversely related to center size (Rc). However, the peak contrast sensitivity is relatively independent of Rc. The ratio of the integrated strength (volume) of the surround to the volume of the center remains relatively constant (median, 0.87) across all three cell classes. This ratio is an excellent predictor of a cell's rolloff in contrast sensitivity at low spatial frequencies: cells with a low surround/center ratio have less low-frequency rolloff. Although M, P, and K cells generally display similar center/surround relationships, differences in center size and the other parameters between the classes distinguish most M, P, and K cells. These findings demonstrate that both similarities and differences in the visual-response properties of primate LGN cells in these three parallel afferent pathways can be explained by basic center/surround relationships.

Afferent Pathways↗
PubMed1992

Contrast gain control in the primate retina: P cells are not X-like, some M cells are.

Primate retinal ganglion cells that project to the magnocellular layers of the lateral geniculate nucleus (M) are much more sensitive to luminance contrast than those ganglion cells projecting to the parvocellular layers (P). We now report that increasing contrast modifies the temporal-frequency response of M cells, but not of P cells. With rising contrast, the M cells' responses to sinusoidal stimuli show an increasing attenuation at low temporal frequencies while the P cells' responses scale uniformly. The characteristic features of M-cell dynamics are well described by a model originally developed for the X and Y cells of the cat, where the hypothesized nonlinear feedback mechanism responsible for this behavior has been termed the contrast gain control (Shapley & Victor, 1978, 1981; Victor, 1987, 1988). These data provide further physiological evidence that the M-cell pathway differs from the P-cell pathway with regard to the functional elements in the retina. Furthermore, the similarity in dynamics between primate M cells and cat X and Y retinal ganglion cells suggests the possibility that P cells, being different from either group, are a primate specialization not found in the retinae of lower mammals.

Animals↗