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Penile vibratory stimulation in the marmoset monkey: a practical alternative to electro-ejaculation, yielding ejaculates of enhanced quality.

The availability of sufficient amounts of spermatozoa of high quality is one of the main limiting factors in reproductive research and development of reproductive technologies in marmoset monkeys (Callithrix jacchus). Penile vibrostimulation (PVS) has been successfully used in semen collection in the squirrel monkey but with poor success rate in the marmoset. We report here on an improved protocol for PVS with a success rate of almost 90%. Ejaculates obtained by PVS were of enhanced quality compared with those obtained by rectal probe electro-ejaculation (RPE). PVS ejaculates contained on average three to fourfold higher numbers of total and motile spermatozoa. Assessment of sperm kinematics using computer-assisted sperm analysis indicated that there are also functional differences between spermatozoa collected by PVS and RPE. Marmoset spermatozoa in samples obtained by RPE swim in a more convoluted manner compared with those obtained by PVS.

Analysis of Variance↗

Marmoset glutathione peroxidases: cDNA sequences, molecular evolution, and gene expression.

BACKGROUND: Dysfunction of the cellular antioxidant system and accumulation of reactive oxygen species are involved in the pathophysiology of diseases such as cardiovascular disease, neurodegenerative disorders, tumors, male infertility and aging. Two gluthathione peroxidases play key roles in the cellular protection against oxidative damage. Glutathione peroxidase (GPx-1) removes cytosolic hydroperoxides while phospholipid-hydroperoxide glutathione peroxidase (GPx-4) is a unique enzyme that reduces phospholipid peroxides in membranes. METHODS: We cloned and sequenced the full-length cDNA for GPx-1 (GenBank: AY966403) and GPx-4 (GenBank: AY966404) from the common marmoset (Callithrix jacchus) in order to create a suitable model for studying human diseases related with oxidative stress. RESULTS: The cDNAs encode a 202 amino acid protein for GPx-1 and a 197 amino acid protein for GPx-4. Both proteins include selenocysteine (Sec, in Gpx-1 at position 48; in GPx-4 at position 73) and showed high homology (>90%) with other mammalian GPxs. The relative levels of mRNA expression for GPx-1 and GPx-4 were determined in different marmoset tissues by quantitative real-time reverse transcriptase-polymerase chain reaction using transcription elongation factor-2 as a reference gene. GPx-1 showed increased levels of expression in the liver, heart and kidney while the highest mRNA levels for GPx-4 were detected in the testis, followed by the liver, lung, kidney and spinal cord. CONCLUSIONS: These findings will be of value for studies designed to assess the role of glutathione peroxidases in non-human primate models for a variety of diseases in which increased oxidative stress has been implicated.

Amino Acid Sequence↗

Evaluation of the contraceptive potential of recombinant human ZP3 and human ZP3 peptides in a primate model: their safety and efficacy.

PROBLEM: The unique recognition events that result in the avid binding of mammalian spermatozoa to the surface of the zona pellucida (ZP) are being exploited in the development of contraceptive vaccines. In this study, the safety and efficacy of a vaccination strategy based on the induction of active immunity against purified, glycosylated, recombinant human ZP3 (rhZP3) has been evaluated in a primate model, Callithrix jacchus. METHOD OF STUDY: Long-term infertility was established after immunization with rhZP3 and the resulting immune sera reacted with rhZP3 on an enzyme-linked immunosorbent assay (ELISA) and immunolocalized exclusively to the outer surface of native ZP on marmoset ovarian sections. However, this contraceptive effect was inevitably associated with the eventual appearance of an ovarian pathology characterized by a depletion of primordial follicles. In an attempt to circumvent this side effect, human ZP3 (hZP3) was epitope mapped and four continuous, immunodominant B-cell epitopes (hZP3(45-64), hZP3(93-110), hZP3(172-190) and hZP3(341-360) were evaluated for contraceptive efficacy in vivo. Using peptide-tetanus toxoid (TT) conjugates to enhance immunogenicity, antipeptide antibodies were raised against these immunogens, which also cross-reacted with rhZP3 on ELISA. In addition, antibodies against hZP3(45-64) and hZP3(172-190) recognized native ZP on marmoset ovarian sections when a microwave technique was used to enhance epitope presentation. RESULTS: No ovarian pathology was observed after the long-term administration of these peptide immunogens, and fertility was suppressed when compared with TT controls but could not be correlated to the antibody titer. CONCLUSION: Clearly, further research is required to identify optimal B-cell epitopes that will reliably induce infertility, free from any ovarian pathology.

Amino Acid Sequence↗

Experimental induction of beta-amyloid plaques and cerebral angiopathy in primates.

Moderate numbers of amyloid plaques with associated argyrophilic dystrophic neurites and cerebral amyloid angiopathy (CAA) but no neurofibrillary tangles (NFTs) were found in the brains of 3 middle-aged common marmosets (Callithrix jacchus) inoculated intracerebrally (i.c.) 6-7 years earlier with brain tissue from a patient with early onset Alzheimer's disease. The plaques and vascular amyloid stained positively with antibodies to beta (A4)-protein. The brains of 3 age-matched control marmosets from the same colony did not show these neuropathological features. beta-amyloid plaques and CAA (but no spongiform encephalopathy) were also found in the brain of a marmoset inoculated with brain tissue from a patient with prion disease with concomitant beta-amyloid plaques and CAA. An occasional beta-amyloid plaque was found in the brains of two marmosets inoculated with brain tissue from elderly patients. No beta-amyloid plaques nor CAA were found in 6 other marmosets who were older than the inoculated marmosets, 10 further marmosets who were slightly younger but who had been inoculated several years previously with brain tissue which did not contain beta-amyloid, and 10 younger marmosets who had been subjected to various neurosurgical procedures. These results suggest that beta-amyloidosis is a transmissible process.

Alzheimer Disease↗

Establishment of a Common Marmoset Lineage Carrying a Frameshift Mutation in SETD1A, a Schizophrenia Risk Gene.

Appropriate histone modifications are essential for maintaining functional chromatin structure and gene expression, and dysfunction of their regulators has been linked to a variety of diseases. Among these modifications, trimethylation of lysine 4 on histone H3 (H3K4me3) is a well-characterized epigenetic mark enriched at transcription start sites of actively transcribed genes. H3K4me3 regulates gene transcription by recruiting transcription factors, facilitating chromatin accessibility, and preventing DNA methylation. In mammals, methylation of H3K4 is catalyzed by a family of histone methyltransferases including SET domain containing 1A (SETD1A), which is primarily responsible for genome-wide deposition of H3K4me2/3. Loss-of-function variants in SETD1A, highlighting its critical role in brain development and cognitive function, are strongly associated with schizophrenia (SCZ) and other neurodevelopmental disorders, but the underlying mechanisms remain largely unclear. To better understand the epigenetic and neurobiological consequences of SETD1A dysfunction, non-human primate models can serve as a useful tool because of their close evolutionary relationship to humans and highly developed cognitive abilities. In this study, we established a genetically engineered common marmoset (Callithrix jacchus) lineage carrying a frameshift mutation in SETD1A, which is, to the best of our knowledge, the first non-human primate lineage carrying a mutation in an epigenetic regulatory gene associated with SCZ, and confirmed germline transmission of the mutant allele. In a comparison between fibroblasts derived from one SETD1A mutant and one wild-type marmoset, the mutant showed a lower SETD1A protein level, modest differences in H3K4me3 deposition, and broader differences in gene expression profiles. Although these molecular observations require validation using additional biological replicates, the establishment of this SETD1A mutant marmoset lineage provides a valuable platform for bridging molecular mechanisms with primate neurobiology and for investigating the role of epigenetic regulation in the pathophysiology of neuropsychiatric and neurodevelopmental disorders.

Animals↗

Cross-protection in nonhuman primates against Argentine hemorrhagic fever.

The susceptibility of the marmoset Callithrix jacchus to Tacaribe virus infection was investigated to perform cross-protection studies between Junin and Tacaribe viruses. Five marmosets inoculated with Tacaribe virus failed to show any signs of disease, any alterations in erythrocyte, leukocyte, reticulocyte, and platelet counts or any changes in hematocrit or hemoglobin values. No Tacaribe virus could be recovered from blood at any time postinfection. Anti-Tacaribe neutralizing antibodies appeared 3 weeks postinfection. The five Tacaribe-infected marmosets and four noninfected controls were challenged with the pathogenic strain of Junin virus on day 60 post-Tacaribe infection. The former group showed no signs of disease, no viremia, and no challenge virus replication, whereas the control group exhibited the typical symptoms of Argentine hemorrhagic fever, high viremia, and viral titers in organs. Soon after challenge, the Tacaribe-protected marmosets synthesized neutralizing antibodies against Junin virus. These results indicate that the marmoset C. jacchus can be considered an experimental model for protection studies with arenaviruses and that the Tacaribe virus could be considered as a potential vaccine against Junin virus.

Animals↗

Isolation of an arenavirus from a marmoset with callitrichid hepatitis and its serologic association with disease.

Callitrichid hepatitis (CH) is an acute, often fatal viral infection of New World primates from the family Callitrichidae. The etiologic agent of CH is unknown. We report here the isolation of an arenavirus from a common marmoset (Callithrix jacchus) with CH by using in vitro cultures of marmoset hepatocytes and Vero-E6 cells. Enveloped virions 67 to 133 nm in diameter with ribosomelike internal structures were seen in infected cultures. Immunofluorescence and Western immunoblot analysis using CH-specific antisera (principally from animals exposed to CH during zoo outbreaks) revealed three antigens in cells infected with this CH-associated virus (CHV). These antigens had the same electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gels as did the nucleocapsid, GP2, and GPC proteins of lymphocytic choriomeningitis virus (LCMV). Monoclonal antibodies specific for these arenavirus proteins also reacted with the three CHV antigens. Conversely, the CH-specific antisera reacted with the nucleocapsid, GP2, and GPC proteins of LCMV. CHV thus appears to be a close antigenic relative of LCMV. The serologic association of CHV with several CH outbreaks implicate it as the etiologic agent of this disease.

Animals↗

Complete genomic sequence of an Epstein-Barr virus-related herpesvirus naturally infecting a new world primate: a defining point in the evolution of oncogenic lymphocryptoviruses.

Callitrichine herpesvirus 3 (CalHV-3) was isolated from a B-cell lymphoma arising spontaneously in the New World primate Callithrix jacchus, the common marmoset. Partial genomic sequence analysis definitively identified CalHV-3 as a member of the Epstein-Barr virus (EBV)-related lymphocryptovirus (LCV) genus and extended the known host range of LCVs beyond humans and Old World nonhuman primates. We have now completed the first genomic sequence of an LCV infecting a New World primate by describing the unique short region, the major internal repeat, and a portion of the unique long region. This portion of the genome contains the putative latent origin of replication and 13 additional open reading frames (ORFs), 5 of which show no homology to any viral or cell genes. One of the novel genes, C5, is a positional homologue for the transformation-essential EBV gene EBNA-2. The marmoset LCV genome is also notable for the absence of viral interleukin-10 and small nonpolyadenylated RNA homologues. Marmoset LCV transcripts encoding putative latent infection nuclear proteins have a common leader sequence that is spliced from the major internal repeat in a manner similar to that of the EBV EBNA-LP, suggesting strong conservation of a common promoter and splicing of these latent infection mRNAs. An EBV LMP2A-like spliced transcript crossing the terminal repeats encodes a unique ORF, C7, with multiple transmembrane domains and tyrosine kinase phosphorylation sites functionally reminiscent of EBV LMP2A. However, the carboxy-terminal location of the candidate phosphotyrosine residues is more reminiscent of the Kaposi's sarcoma-associated herpesvirus K15 gene and provides potential evidence of an evolutionary transition from rhadinoviruses to lymphocryptoviruses. The unusual gene repertoire of the marmoset LCV differentiates ancestral viral genes likely present in an LCV progenitor from viral genes acquired later as primates and LCV coevolved, providing a defining point in the evolution of oncogenic LCVs.

Amino Acid Sequence↗

Development of a GB virus B marmoset model and its validation with a novel series of hepatitis C virus NS3 protease inhibitors.

GB virus B (GBV-B), a flavivirus closely related to HCV, has previously been shown to infect and replicate to high titers in tamarins (Saguinus sp.). This study describes the use of GBV-B infection and replication in the common marmoset (Callithrix jacchus) for the successful development and validation of a surrogate animal model for hepatitis C virus (HCV). Infection of marmosets with GBV-B produced a viremia that peaked at 10(8) to 10(9) genome copies/ml for a period of 40 to 60 days followed by viral clearance at 60 to 80 days postinfection. Passage of the initial tamarin-derived GBV-B in marmosets produced an infectious stock that gave a more reproducible and consistent infection in the marmoset. Titration of the virus stocks in vivo indicated that they contained 1 infectious unit for every 1,000 genome copies. Cultures of primary marmoset hepatocytes were also successfully infected with GBV-B, with high levels of virus detected in supernatants and cells for up to 14 days postinfection. Treatment of GBV-B-infected hepatocyte cultures with a novel class of HCV protease inhibitor (pyrrolidine 5,5 trans-lactams) reduced viral levels by more than 2 logs. Treatment of GBV-B-infected marmosets with one such inhibitor resulted in a 3-log drop in serum viral titer over 4 days of therapy. These studies provide the first demonstration of the in vivo efficacy of a small-molecule inhibitor for HCV in an animal model and illustrate the utility of GBV-B as a surrogate animal model system for HCV.

Animals↗

Experimental transmission of BSE and scrapie to the common marmoset.

Two young male common marmosets (Callithrix jacchus) were injected intracerebrally and intraperitoneally with a crude brain homogenate prepared from a cow with bovine spongiform encephalopathy (BSE). Two other marmosets were similarly injected with brain homogenate from a sheep with natural scrapie. The two animals injected with scrapie material developed neurological signs 38 and 42 months after injection and the two animals injected with BSE material developed neurological signs after 46 and 47 months. Post mortem examination of the brains revealed spongiform encephalopathy especially in the basal nuclei and diencephalon of all the animals and, in addition, involvement of the cerebral cortex of the marmosets injected with scrapie material. The experiment extends the host range of experimental BSE to include a primate species.

Animals↗

beta-Adrenergic control of lipolysis in primate white fat cells: a comparative study with nonprimate mammals.

The beta-adrenoceptor subtypes involved in the control of lipolysis in white fat cells of rat, dog, marmoset (Callithrix jacchus), baboon (Papio papio), macaque (Macaca fascicularis), and human were compared. In all species [3H]CGP-12177 binding (up to 3 nM) indicated the existence of a homogeneous population of binding sites in fat cell membranes, and competition studies showed that beta 1- and beta 2-adrenoceptors were present. Selective beta 1 or beta 2-adrenoceptor agonists induced lipolysis. The efficiencies of isoproterenol and norepinephrine were similar. The use of selective beta 3-adrenoceptor agonists revealed that BRL-37344 and CL-316243 were full agonists, whereas CGP-12177 and SR-58611A were partial agonists in rat and dog white fat cells. beta 3-Agonists partially stimulated lipolysis in the marmoset, while CGP-12177 was weakly active in the baboon. In macaque and human fat cells, beta 3-agonists were ineffective. The lipolytic effect of norepinephrine involves beta 1-and/or beta 2-adrenoceptors in baboon, macaque, and human. The baboon and macaque constitute valuable models for studying the beta-adrenergic control of lipolysis.

Adipocytes↗

Sensory-motor interaction in the primate auditory cortex during self-initiated vocalizations.

Little is known about sensory-motor interaction in the auditory cortex of primates at the level of single neurons and its role in supporting vocal communication. The present study investigated single-unit activities in the auditory cortex of a vocal primate, the common marmoset (Callithrix jacchus), during self-initiated vocalizations. We found that 1) self-initiated vocalizations resulted in suppression of neural discharges in a majority of auditory cortical neurons. The vocalization-induced inhibition suppressed both spontaneous and stimulus-driven discharges. Suppressed units responded poorly to external acoustic stimuli during vocalization. 2) Vocalization-induced suppression began several hundred milliseconds prior to the onset of vocalization. 3) The suppression of cortical discharges reduced neural firings to below the rates expected from a unit's rate-level function, adjusted for known subcortical attenuation, and therefore was likely not entirely caused by subcortical attenuation mechanisms. 4) A smaller population of auditory cortical neurons showed increased discharges during self-initiated vocalizations. This vocalization-related excitation began after the onset of vocalization and is likely the result of acoustic feedback. Units showing this excitation responded nearly normally to external stimuli during vocalization. Based on these findings, we propose that the suppression of auditory cortical neurons, possibly originating from cortical vocal production centers, acts to increase the dynamic range of cortical responses to vocalization feedback for self monitoring. The excitatory responses, on the other hand, likely play a role in maintaining hearing sensitivity to the external acoustic environment during vocalization.

Acoustic Stimulation↗

Representation of spectral and temporal envelope of twitter vocalizations in common marmoset primary auditory cortex.

Cortical sensitivity in representations of behaviorally relevant complex input signals was examined in recordings from primary auditory cortical neurons (AI) in adult, barbiturate-anesthetized common marmoset monkeys (Callithrix jacchus). We studied the robustness of distributed responses to natural and degraded forms of twitter calls, social contact vocalizations comprising several quasi-periodic phrases of frequency and AM. We recorded neuronal responses to a monkey's own twitter call (MOC), degraded forms of their twitter call, and sinusoidal amplitude modulated (SAM) tones with modulation rates similar to those of twitter calls. In spectral envelope degradation, calls with narrowband channels of varying bandwidths had the same temporal envelope as a natural call. However, the carrier phase was randomized within each narrowband channel. In temporal envelope degradation, the temporal envelope within narrowband channels was filtered while the carrier frequencies and phases remained unchanged. In a third form of degradation, noise was added to the natural calls. Spatiotemporal discharge patterns in AI both within and across frequency bands encoded spectrotemporal acoustic features in the call although the encoded response is an abstract version of the call. The average temporal response pattern in AI, however, was significantly correlated with the average temporal envelope for each phrase of a call. Response entrainment to MOC was significantly correlated with entrainment to SAM stimuli at comparable modulation frequencies. Sensitivity of the response patterns to MOC was substantially greater for temporal envelope than for spectral envelope degradations. The distributed responses in AI were robust to additive continuous noise at signal-to-noise ratios > or =10 dB. Neurophysiological data reflecting response sensitivity in AI to these forms of degradation closely parallel human psychophysical results on the intelligibility of degraded speech in quiet and noisy conditions.

Acoustic Stimulation↗

The nature of V1 neural responses to 2D moving patterns depends on receptive-field structure in the marmoset monkey.

A plaid pattern is formed when two sinusoidal gratings of different orientations are added together. Previous work has shown that V1 neurons selectively encode the direction and orientation of the component gratings in a moving plaid but not the direction of the plaid itself (Movshon et al. 1985). We recorded the responses of 49 direction-selective neurons to moving gratings and plaid patterns in area V1 of the anesthetized marmoset monkey (Callithrix jacchus). The responses of V1 neurons to rectangular patches of varying lengths and widths containing gratings of optimal spatial frequency were used to measure size and aspect ratio of the receptive-field subunits. We measured responses to plaid patterns moving in different directions and graded the magnitude of the response to the direction of motion of the plaid and the response to the direction of motion of the component gratings. We found significant correlations between receptive-field structure and the type and strength of its response to moving plaid patterns. The strength of pattern and component responses was significantly correlated with the interrelated properties of direction tuning width (Spearman's r = 0.82, P < 0.001), and receptive-field subunit aspect ratio (Spearman's r = -0.79, P < 0.001). Neurons with broad direction tuning and short, wide receptive-field subunits gave their greatest response when the plaid moved in their preferred direction. Conversely, neurons with narrow direction tuning and long, narrow receptive-field subunits gave their greatest responses when the plaid moved in a direction such that one of its components moved in the preferred direction.

Animals↗

Virtual vocalization stimuli for investigating neural representations of species-specific vocalizations.

Most studies investigating neural representations of species-specific vocalizations in non-human primates and other species have involved studying neural responses to vocalization tokens. One limitation of such approaches is the difficulty in determining which acoustical features of vocalizations evoke neural responses. Traditionally used filtering techniques are often inadequate in manipulating features of complex vocalizations. Furthermore, the use of vocalization tokens cannot fully account for intrinsic stochastic variations of vocalizations that are crucial in understanding the neural codes for categorizing and discriminating vocalizations differing along multiple feature dimensions. In this work, we have taken a rigorous and novel approach to the study of species-specific vocalization processing by creating parametric "virtual vocalization" models of major call types produced by the common marmoset (Callithrix jacchus). The main findings are as follows. 1) Acoustical parameters were measured from a database of the four major call types of the common marmoset. This database was obtained from eight different individuals, and for each individual, we typically obtained hundreds of samples of each major call type. 2) These feature measurements were employed to parameterize models defining representative virtual vocalizations of each call type for each of the eight animals as well as an overall species-representative virtual vocalization averaged across individuals for each call type. 3) Using the same feature-measurement that was applied to the vocalization samples, we measured acoustical features of the virtual vocalizations, including features not explicitly modeled and found the virtual vocalizations to be statistically representative of the callers and call types. 4) The accuracy of the virtual vocalizations was further confirmed by comparing neural responses to real and synthetic virtual vocalizations recorded from awake marmoset auditory cortex. We found a strong agreement between the responses to token vocalizations and their synthetic counterparts. 5) We demonstrated how these virtual vocalization stimuli could be employed to precisely and quantitatively define the notion of vocalization "selectivity" by using stimuli with parameter values both within and outside the naturally occurring ranges. We also showed the potential of the virtual vocalization stimuli in studying issues related to vocalization categorizations by morphing between different call types and individual callers.

Acoustic Stimulation↗

Sense of taste in a New World monkey, the common marmoset. II. Link between behavior and nerve activity.

In a previous study, we characterized the gustatory system of a New World monkey the common marmoset, Callithrix jacchus jacchus, with electrophysiological techniques by recording from taste fibers of the chorda tympani proper (CT) and glossopharyngeal (NG) nerves. Hierarchical cluster analysis identified three clusters of taste fibers: S fibers, responding predominantly to sweeteners, Q fibers, responding predominantly to bitter stimuli, and H fibers, responding predominantly to acids. In this study, we employed two behavioral techniques, the two-bottle preference (TBP) and conditioned taste aversion (CTA), to study the taste of the compounds used in the previous electrophysiological study. The results showed that compounds that did not stimulate any taste fibers were neither preferred nor rejected. Compounds that activated only S fibers were always preferred over water. When aversion to sucrose was created by the CTA method, these compounds were rejected. Compounds that activated Q fibers were rejected and consumed less than water. We studied the relationship between intake and net response from S and Q fibers in the CT and NG nerves. Intake was measured as a preference ratio in TBP test. The net response was defined as: (S(CT) + S(NG)) - (Q(CT) + Q(NG)), where S(CT) + S(NG) denotes the sum of the responses in S fibers of the CT and NG nerves. Similarly, Q(CT) + Q(NG) represents the sum of the responses in Q fibers of the CT and NG nerves. The relationship between intake and the Net response was linear with a Pearson correlation coefficient 0.85. This study supports our hypothesis that intake is influenced by S and Q fibers, where S fibers serve as a hedonically positive input and Q fibers as a hedonically negative input.

Animals↗

Representation of a species-specific vocalization in the primary auditory cortex of the common marmoset: temporal and spectral characteristics.

1. The temporal and spectral characteristics of neural representations of a behaviorally important species-specific vocalization were studied in neuronal populations of the primary auditory cortex (A1) of barbiturate-anesthetized adult common marmosets (Callithrix jacchus), using both natural and synthetic vocalizations. The natural vocalizations used in electrophysiological experiments were recorded from the animals under study or from their conspecifics. These calls were frequently produced in vocal exchanges between members of our marmoset colony and are part of the well-defined and highly stereotyped vocal repertoire of this species. 2. The spectrotemporal discharge pattern of spatially distributed neuron populations in cortical field A1 was found to be correlated with the spectrotemporal acoustic pattern of a complex natural vocalization. However, the A1 discharge pattern was not a faithful replication of the acoustic parameters of a vocalization stimulus, but had been transformed into a more abstract representation than that in the auditory periphery. 3. Subpopulations of A1 neurons were found to respond selectively to natural vocalizations as compared with synthetic variations that had the same spectral but different temporal characteristics. A subpopulation responding selectively to a given monkey's call shared some but not all of its neuronal memberships with other individual-call-specific neuronal subpopulations. 4. In the time domain, responses of individual A1 units were phase-locked to the envelope of a portion of a complex vocalization, which was centered around a unit's characteristic frequency (CF). As a whole, discharges of A1 neuronal populations were phase-locked to discrete stimulus events but not to their rapidly changing spectral contents. The consequence was a reduction in temporal complexity and an increase in cross-population response synchronization. 5. In the frequency domain, major features of the stimulus spectrum were reflected in rate-CF profiles. The spectral features of a natural call were equally or more strongly represented by a subpopulation of A1 neurons that responded selectively to that call as compared with the entire responding A1 population. 6. Neuronal responses to a complex call were distributed very widely across cortical field A1. At the same time, the responses evoked by a vocalization scattered in discrete cortical patches were strongly synchronized to stimulus events and to each other. As a result, at any given time during the course of a vocalization, a coherent representation of the integrated spectrotemporal characteristics of a particular vocalization was present in a specific neuronal population. 7. These results suggest that the representation of behaviorally important and spectrotemporally complex species-specific vocalizations in A1 is 1) temporally integrated and 2) spectrally distributed in nature, and that the representation is carried by spatially dispersed and synchronized cortical cell assemblies that correspond to each individual's vocalizations in a specific and abstracted way.

Acoustic Stimulation↗

Parallel processing in cerebral cortex of the marmoset monkey: effect of reversible SI inactivation on tactile responses in SII.

1. Responsiveness within the hand region of the second somatosensory area of cortex (SII) was investigated in the marmoset monkey (Callithrix jacchus) in association with cooling-induced, reversible inactivation of the primary somatosensory area, SI. The aims were to determine whether thalamocortical systems in this primate species are organized according to a serial scheme in which tactile information is conveyed from the thalamus to SI and thence to SII as the next hierarchical level of processing and to establish whether primates are fundamentally different, in this respect, from mammals in which tactile information is conveyed in parallel from the thalamus to both SI and SII. 2. Inactivation of the SI had area was achieved when the temperature at the face of the silver cooling block over this SI region was lowered to < or = 13 degrees C. Inactivation was confirmed by abolition of the SI surface potential evoked by a brief tap stimulus to the hand and by the abolition of responsiveness in single SI neurons located beneath and around the edge of the block. 3. The effect of SI inactivation on SII-evoked potentials was investigated in 20 experiments by simultaneous recording of the SI- and SII-evoked potentials. The SII response was never abolished and was unchanged in the majority (12/20) of experiments. In the remainder, the SII-evoked potentials underwent a reduction in amplitude that was usually < 30% but never > 50%. 4. Tactile responsiveness was examined quantitatively in 47 individual SII neurons of different functional classes before, during, and after the inactivation of SI. Controlled tactile stimuli consisted of trains of sinusoidal vibration or rectangular pulses delivered to the glabrous or hairy skin of the hand. 5. Thirteen of the 47 SII neurons (28%) were unaffected in their response levels in association with SI inactivation. The remaining 34 SII neurons underwent some reduction in responsiveness, but in only 6% (3/47) was responsiveness abolished by SI inactivation. As the same range of functional classes of tactile neurons were represented among the affected and unaffected SII neurons, there was no evidence for a differential susceptibility among SII tactile neurons to the effect of SI inactivation. 6. Where reductions in amplitude of the SII-evoked potential or in response levels of SII neurons were observed, the effects were not attributable to direct spread of cooling from SI to the SII hand area as there was no cooling-induced prolongation of either the evoked potential or spike waveform in SII, an effect that is known to precede cooling-induced reductions in responsiveness. 7. These lines of evidence indicate that reductions in SII responsiveness in association with SI inactivation may be attributable to a loss of a background facilitatory influence rather than to a blockage of a component of peripheral input that comes over a putative serial path to SII via SI. First, as SI was cooled, there was a progressive increase in latency and time course of the SI responses before their disappearance, but no comparable delay in the SII responses as might be expected if SI were placed earlier than SII in a strict hierarchical scheme of thalamocortical processing. Second, SI inactivation failed to bring about a tightening in the phase-locking of SII responses to vibrotactile stimuli as might have been expected if the inputs to the SII neurons come via both a direct path from the thalamus and an indirect intracortical path via SI. Blockage of the indirect intracortical pathway through SI might be expected to reduce temporal dispersion in the input to SII neurons and result in an improvement in phase-locking in the SII responses to skin vibration. Third, the background activity of some SII neurons was reduced during SI inactivation along with the reduction in their responses to tactile stimulation.

Animals↗