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Selvanayagam, J.

Publications and source records attributed to Selvanayagam, J..

11 recordsLinked to original sources

Influence of distractors on spatial working memory and neural activity in marmoset prefrontal cortex

The prefrontal cortex (PFC) plays a critical role in maintaining working memory (WM) representations while filtering irrelevant distractors. In macaques, PFC neurons exhibit persistent delay period activity that is robust to distractor interference. The common marmoset has emerged recently as a complementary primate model for investigating the neural basis of cognitive processes including WM, in part because the relatively lissencephalic cortex of this species enables laminar recordings which could provide substantial insight into the microcircuit basis of these functions. It remains unknown however, whether marmoset WM performance is robust to distractors presented during delay periods of WM tasks, and how such distractor filtering may be implemented in PFC circuits. Here, we addressed this gap by conducting wireless recordings of PFC in freely moving marmosets performing a touchscreen-based delayed-match-to-location (DML) task in which a salient visual distractor was presented during the delay period on a subset of trials. Marmosets maintained WM performance on distractor trials, showing a decrease in accuracy of only 5%. Consistent with prior observations in both the macaque and marmoset models, we found that many PFC neurons exhibited activity related to the stimulus sample, during the delay period, and around the time of the behavioural response. In a subset of neurons, we observed distractor-mediated modulations of persistent delay period activity which were associated with a greater incidence of performance errors on the DML task. These findings reveal that marmoset WM is robust to distractor interference, and that the PFC mechanisms instantiating WM and distractor filtering are conserved in this primate species. Taken together, they support the common marmoset as a complementary model for investigating the contribution of PFC circuits to mnemonic and attentional processes.

neuroscience↗

Neural activity for complex sounds in the marmoset medial prefrontal cortex

Vocalizations play an important role in the daily life of nonhuman primates and are likely precursors of human language. Recent functional imaging studies in the highly vocal common marmoset (Callithrix jacchus) have suggested that medial prefrontal cortex area 32 may be a part of a vocalization-processing network but the response properties of area 32 neurons to auditory stimuli remain unknown. Here, we performed electrophysiological recordings in area 32 with high-density Neuropixels probes and characterized neuronal responses to a variety of sounds including conspecific vocalizations. More than half of the neurons in area 32 responded to conspecific vocalizations and other complex auditory stimuli. These responses exhibited dynamics consisting of an initially non-selective reduction in neural activity, followed by an increase in activity that immediately conveyed sound selectivity. Our findings demonstrate that primate mPFC area 32 plays a critical role in processing species-specific and biologically relevant sounds.

neuroscience↗

Functional Specialization and Distributed Processing across Marmoset Lateral Prefrontal Subregions

A prominent aspect of the organization of primate lateral prefrontal cortex (lPFC) is its division into a number of cytoarchitecturally distinct subregions. Investigations in macaque lPFC using neurophysiological approaches have provided much insight into the functions associated with these subregions; however, our understanding is based largely on a patchwork of findings from many studies and across many animals, rarely covering the entire lPFC in individual subjects. Here, we leveraged the small size and lissencephalic cortex of the common marmoset (Callithrix jacchus) to characterize the responses of large numbers of single lPFC neurons to a diverse collection of test stimuli recorded across sets of lPFC subregions using high-density microelectrode arrays. Untethered extracellular electrophysiological recordings were obtained from two adult marmosets with 4 x 4 mm 96-channel Utah arrays implanted in lPFC, covering areas 8aD, 8aV, 9, 10, 46D, 46V and 47. We employed a test battery comprised of a variety of visual stimuli including faces and body parts, auditory stimuli including marmoset calls, and a spatial working memory task. Task-modulated units and units responsive to different stimulus modalities were distributed throughout the lPFC. Visual, auditory and call-selective units were distributed across all lPFC subregions. Neurons with contralateral visual receptive fields were found in 8aV and 8aD. Neurons responsive to faces and saccade-related units were found in 8aV, 8aD, 10, 46V and 47. These findings demonstrate that responses to some stimuli are relatively restricted within specific lPFC subregions, while others are more distributed throughout the marmoset lPFC.

neuroscience↗

Laminar Dynamics of Target Selection in the Posterior Parietal Cortex of the Common Marmoset

The lateral intraparietal area (LIP) plays a crucial role in target selection and attention in primates, but the laminar microcircuitry of this region is largely unknown. To address this, we used ultra-high density laminar electrophysiology with Neuropixels probes to record neural activity in the posterior parietal cortex (PPC) of two adult marmosets while they performed a simple visual target selection task. Our results reveal neural correlates of visual target selection in the marmoset, similar to those observed in macaques and humans, with distinct timing and profiles of activity across cell types and cortical layers. Notably, a greater proportion of neurons exhibited stimulus related activity in superficial layers whereas a greater proportion of infragranular neurons exhibited significant post-saccadic activity. Stimulus-related activity was first observed in granular layer putative interneurons, whereas target discrimination activity emerged first in supragranular layers putative pyramidal neurons, supporting a canonical laminar circuit underlying visual target selection in marmoset PPC. These findings provide novel insights into the neural basis of visual attention and target selection in primates.

neuroscience↗

Gaze patterns and brain activations in humans and marmosets in the Frith-Happe; theory-of-mind animation task

Theory of Mind (ToM) refers to the ability to ascribe mental states to other individuals. This process is so strong that it extends even to the attribution of mental states to animations depicting interacting simple geometric shapes, such as in the Frith-Happe animations in which two triangles move either purposelessly (Random condition), or as if one triangle is reacting to the other triangles mental state (ToM condition). Currently, there is no evidence that nonhuman primates attribute mental states to moving abstract shapes. Here we investigated whether highly social marmosets (Callithrix jacchus) process ToM and Random Frith-Happe animations differently. Our results show that marmosets and humans (1) follow more closely one of the triangles during the observation of ToM compared to Random animations, and (2) activate large and comparable brain networks when viewing ToM compared to Random animations. These findings indicate that marmosets, like humans, process ToM animations differently from Random animations.

neuroscience↗

Delay-related activity in marmoset prefrontal cortex

Persistent delay-period activity in prefrontal cortex (PFC) has long been regarded as a neural signature of working memory (WM). Electrophysiological investigations in macaque PFC have provided much insight into WM mechanisms, however a barrier to understanding is the fact that a portion of PFC lies buried within the principal sulcus in this species and is inaccessible for laminar electrophysiology or optical imaging. The relatively lissencephalic cortex of the New World common marmoset (Callithrix jacchus) circumvents such limitations. It remains unknown however, whether marmoset PFC neurons exhibit persistent activity. Here, we addressed this gap by conducting wireless electrophysiological recordings in PFC of marmosets performing a delayed-match-to-location task on a home cage-based touchscreen system. As in macaques, marmoset PFC neurons exhibited sample, delay, and response-related activity that was directionally tuned and linked to correct task performance. Models constructed from population activity consistently and accurately predicted stimulus location throughout the delay period, supporting a framework of delay activity in which mnemonic representations are relatively stable in time. Taken together, our findings support the existence of common neural mechanisms underlying WM performance in PFC of macaques and marmosets, and thus validate the marmoset as a suitable model animal for investigating the microcircuitry underlying WM.

neuroscience↗

Ketamine disrupts gaze patterns during face viewing in the common marmoset

Faces are stimuli of critical importance for primates. The common marmoset (Callithrix jacchus) is a promising model for investigations of face processing, as this species possesses oculomotor and face processing networks resembling those of macaques and humans. Face processing is often disrupted in neuropsychiatric conditions such as schizophrenia (SZ) and thus it is important to recapitulate underlying circuitry dysfunction preclinically. The N-Methyl-D-aspartate (NMDA) non-competitive antagonist ketamine has been used extensively to model the cognitive symptoms of SZ. Here, we investigated the effects of a subanesthetic dose of ketamine on oculomotor behaviour in marmosets during face viewing. Four marmosets received systemic ketamine or saline injections while viewing phase-scrambled or intact videos of conspecifics faces. To evaluate effects of ketamine on scan paths during face viewing, we identified regions of interest in each face video, and classified locations of saccade onsets and landing positions within these areas. A preference for the snout over eye regions was observed following ketamine administration. In addition, regions in which saccades landed could be significantly predicted by saccade onset region in the saline but not the ketamine condition. No significant drug effects were observed for phase-scrambled videos. Effects on saccade control were limited to a reduction in saccade amplitudes during viewing of scrambled videos. Thus, ketamine induced a significant disruption of scan paths during viewing of conspecific faces but limited effects on saccade motor control. These findings support the use of ketamine in marmosets for investigating changes in neural circuits underlying social cognition in neuropsychiatric disorders.

neuroscience↗

Arabidopsis bZIP11 is a susceptibility factor during Pseudomonas syringae infection

AO_SCPLOWBSTRACTC_SCPLOWThe induction of plant nutrient secretion systems is critical for successful pathogen infection. Some bacterial pathogens, e.g. Xanthomonas species, use TAL (transcription activator-like) effectors to induce transcription of SWEET sucrose efflux transporters. Pseudomonas syringae pathovar (pv.) tomato strain DC3000 lacks TAL effectors, yet is able to induce multiple SWEETs in Arabidopsis thaliana by unknown mechanisms. Since bacteria require other nutrients besides sugars for efficient reproduction, we hypothesized that Pseudomonas may depend on host transcription factors involved in secretory programs to increase access to essential nutrients. Bioinformatic analyses identified the Arabidopsis basic-leucine zipper transcription factor bZIP11 as a potential regulator of nutrient transporters, including SWEETs and UmamiT amino acid transporters. Inducible downregulation of bZIP11 expression in Arabidopsis resulted in reduced growth of P. syringae pv. tomato strain DC3000, whereas inducible overexpression of bZIP11 resulted in increased bacterial growth, supporting the hypothesis that bZIP11 regulated transcription programs are essential for maximal pathogen titer in leaves. Our data are consistent with a model in which a pathogen alters host transcription factor expression upstream of secretory transcription networks to promote nutrient efflux from host cells.

plant biology↗

Face selective patches in marmoset frontal cortex

Primates have evolved the ability transmit important social information through facial expression. In humans and macaque monkeys, socially relevant face processing is accomplished via a distributed cortical and subcortical functional network that includes specialized patches in anterior cingulate cortex and lateral prefrontal cortex, regions usually associated with high-level cognition. It is unclear whether a similar network exists in New World primates, who diverged ~35 million years from Old World primates and have a less elaborated frontal cortex. The common marmoset (Callithrix jacchus) is a small New World primate that is ideally placed to address this question given the complex social repertoire inherent to this species (e.g., observational social learning; imitation; cooperative antiphonal calling). Here, we investigated the existence of a putative high-level face processing network in marmosets by employing ultra-high field (9.4 Tesla) task-based functional MRI (fMRI). We demonstrated that, like Old World primates, marmosets show differential activation in anterior cingulate cortex and lateral prefrontal cortex while they view socially relevant videos of marmoset faces. We corroborate the locations of these frontal regions by demonstrating both functional (via resting-state fMRI) and structural (via cellular-level tracing) connectivity between these regions and temporal lobe face patches. Given the evolutionary separation between macaques and marmosets, our results suggest this frontal network specialized for social face processing predates the separation between Platyrrhini and Catarrhine. These results give further credence to the marmoset as a viable preclinical modelling species for studying human social disorders.

neuroscience↗

Single unit activity in marmoset posterior parietal cortex in a gap saccade task

Abnormal saccadic eye movements can serve as biomarkers for patients with several neuropsychiatric disorders. To investigate cortical control mechanisms of saccadic responses, the common marmoset (Callithrix jacchus) is a promising non-human primate model. Their lissencephalic brain allows for accurate targeting of homologues of sulcal areas in the macaque brain. Here we recorded single unit activity in the posterior parietal cortex of two marmosets using chronic microelectrode arrays, while the monkeys performed a saccadic task with Gap trials (stimulus onset lagged fixation point offset by 200ms) interleaved with Step trials (fixation point disappeared when the peripheral stimulus appeared). Both marmosets showed a gap effect--shorter saccadic reaction times (SRTs) in Gap vs. Step trials. On average, stronger gap-period response across the entire neuronal population preceded shorter SRTs on trials with contralateral targets, although this correlation was stronger among the 15% gap neurons, which responded significantly during the gap. We also found 39% target neurons with significant visual target-related responses, which were stronger in Gap trials and correlated with the SRTs better than the remaining cells. Compared with slow saccades, fast saccades were preceded by both stronger gap-related and target-related response in all PPC neurons, regardless of whether such response reached significance. Our findings suggest that the PPC in the marmoset contains an area that is involved in the modulation of saccadic preparation and plays roles comparable to those of area LIP in macaque monkeys in eye movements.\n\nSIGNIFICANCE STATEMENTAbnormal saccadic eye movements can serve as biomarkers for different neuropsychiatric disorders. So far, processes of cerebral cortical control of saccades are not fully understood. Non-human primates are ideal models for studying such processes, and the marmoset is especially advantageous since their smooth cortex permits laminar analyses of cortical microcircuits. Using electrode arrays implanted in the posterior parietal cortex of marmosets, we found neurons responsive to key periods of a saccadic task in a manner that contribute to cortical modulation of saccadic preparation. Notably, this signal was correlated with subsequent saccadic reaction times and was present in the entire neuronal population. We suggest that the marmoset model will shed new light on the cortical mechanisms of saccadic control.

neuroscience↗

Functional localization of the frontal eye fields in the common marmoset using microstimulation

The frontal eye field (FEF) is a critical region for the deployment of overt and covert spatial attention. While investigations in the macaque continue to provide insight into the neural underpinnings of the FEF, due to its location within a sulcus the macaque FEF is virtually inaccessible to electrophysiological techniques such as high-density and laminar recordings. With a largely lissencephalic cortex, the common marmoset (Callithrix jacchus) is a promising alternative primate model for studying FEF microcircuitry. Putative homologies have been established with the macaque FEF on the basis of cytoarchitecture and connectivity, however physiological investigation in awake, behaving marmosets is necessary to physiologically locate this area. Here we addressed this gap using intracortical microstimulation in a broad range of frontal cortical areas in marmosets. We implanted marmosets with 96-channel Utah arrays and applied microstimulation trains while they freely viewed video clips. We evoked short-latency fixed vector saccades at low currents (<50 A) in areas 45, 8aV, 8C and 6DR. We observed a topography of saccade direction and amplitude consistent with findings in macaques and humans; we observed small saccades in ventrolateral FEF and large saccades combined with contralateral neck and shoulder movements encoded in dorsomedial FEF. Our data provide compelling evidence supporting homology between marmoset and macaque FEF and suggest the marmoset is a useful primate model for investigating FEF microcircuitry and its contributions to oculomotor and cognitive functions.\n\nSignificance StatementThe frontal eye field (FEF) is a critical cortical region for overt and covert spatial attention. The microcircuitry of this area remains poorly understood, as in the macaque, the most commonly used model, it is embedded within a sulcus and is inaccessible to modern electrophysiological and optical imaging techniques. The common marmoset is a promising alternative primate model due to its lissencephalic cortex and potential for genetic manipulation. However, evidence for homologous cortical areas in this model remains limited and unclear. Here we applied microstimulation in frontal cortical areas in marmosets to physiologically identify the FEF. Our results provide compelling evidence for a frontal eye field in the marmoset, and suggest that the marmoset is a useful model for FEF microcircuitry.

neuroscience↗