Samuel U. Nummela

The hippocampus comprises two neural signals—place cells and θ oscillations—that contribute to facets of spatial navigation. Although their complementary relationship has been well established in rodents, their respective contributions in the primate brain during free navigation remains unclear. Here, we recorded neural activity in the hippocampus of freely moving marmosets as they naturally explored a spatial environment to more explicitly investigate this issue. We report place cells in marmoset hippocampus during free navigation that exhibit remarkable parallels to analogous neurons in other mammalian species. Although θ oscillations were prevalent in the marmoset hippocampus, the patterns of activity were notably different than in other taxa. This local field potential oscillation occurred in short bouts (approximately .4 s)—rather than continuously—and was neither significantly modulated by locomotion nor consistently coupled to place-cell activity. These findings suggest that the relationship between place-cell activity and θ oscillations in primate hippocampus during free navigation differs substantially from rodents and paint an intriguing comparative picture regarding the neural basis of spatial navigation across mammals.

Ferrets have become a standard animal model for the development of early visual stages. Less is known about higher-level vision in ferrets, both during development and in adulthood. Here, as a step towards establishing higher-level vision research in ferrets, we used behavioral experiments to test the motion and form integration capacity of adult ferrets. Motion integration was assessed by training ferrets to discriminate random dot kinematograms (RDK) based on their direction. Task difficulty was varied systematically by changing RDK coherence levels, which allowed the measurement of motion integration thresholds. Form integration was measured analogously by training ferrets to discriminate linear Glass patterns of varying coherence levels based on their orientation. In all experiments, ferrets proved to be good psychophysical subjects that performed tasks reliably. Crucially, the behavioral data showed clear evidence of perceptual motion and form integration. In the monkey, motion and form integration are usually associated with processes occurring in higher-level visual areas. In a second set of experiments, we therefore tested whether PSS, a higher-level motion area in the ferret, could similarly support motion integration behavior in this species. To this end, we measured responses of PSS neurons to RDK of different coherence levels. Indeed, neurometric functions for PSS were in good agreement with the behaviorally derived psychometric functions. In conclusion, our experiments demonstrate that ferrets are well suited for higher-level vision research.

Communication is an inherently interactive process that weaves together the fabric of both human and nonhuman primate societies. To investigate the properties of the primate brain during active social signaling, we recorded the responses of frontal cortex neurons as freely moving marmosets engaged in conversational exchanges with a visually occluded virtual marmoset. We found that small changes in firing rate (∼1 Hz) occurred across a broadly distributed population of frontal cortex neurons when marmosets heard a conspecific vocalization, and that these changes corresponded to subjects9 likelihood of producing or withholding a vocal reply. Although the contributions of individual neurons were relatively small, large populations of neurons were able to clearly distinguish between these social contexts. Most significantly, this social context-dependent change in firing rate was evident even before subjects heard the vocalization, indicating that the probability of a conversational exchange was determined by the state of the frontal cortex at the time a vocalization was heard, and not by a decision driven by acoustic characteristics of the vocalization. We found that changes in neural activity scaled with the length of the conversation, with greater changes in firing rate evident for longer conversations. These data reveal specific and important facets of this neural activity that constrain its possible roles in active social signaling, and we hypothesize that the close coupling between frontal cortex activity and this natural, active primate social-signaling behavior facilitates social-monitoring mechanisms critical to conversational exchanges. SIGNIFICANCE STATEMENT We provide evidence for a novel pattern of neural activity in the frontal cortex of freely moving, naturally behaving, marmoset monkeys that may facilitate natural primate conversations. We discovered small (∼1 Hz), but reliable, changes in neural activity that occurred before marmosets even heard a conspecific vocalization that, as a population, almost perfectly predicted whether subjects would produce a vocalization in response. The change in the state of the frontal cortex persisted throughout the conversation and its magnitude scaled linearly with the length of the interaction. We hypothesize that this social context-dependent change in frontal cortex activity is supported by several mechanisms, such as social arousal and attention, and facilitates social monitoring critical for vocal coordination characteristic of human and nonhuman primate conversations.

The common marmoset has attracted increasing interest as a model for visual neuroscience. A measurement of fundamental importance to ensure the validity of visual studies is spatial acuity. The marmoset has excellent acuity that has been reported at the fovea to be nearly half that of the human (Ordy and Samorajski []: Vision Res 8:1205–1225), a value that is consistent with them having similar photoreceptor densities combined with their smaller eye size (Troilo et al. []: Vision Res 33:1301–1310). Of interest, the marmoset exhibits a higher proportion of cones than rods in peripheral vision than human or macaque, which in principle could endow them with better peripheral acuity depending on how those signals are pooled in subsequent processing. Here, we introduce a simple behavioral paradigm to measure acuity and then test how acuity in the marmoset scales with eccentricity. We trained subjects to fixate a central point and detect a peripheral Gabor by making a saccade to its location. First, we found that accurate assessment of acuity required correction for myopia in all adult subjects. This is an important point because marmosets raised in laboratory conditions often have mild to severe myopia (Graham and Judge []: Vision Res 39:177–187), a finding that we confirm, and that would limit their utility for studies of vision if uncorrected. With corrected vision, we found that their acuity scales with eccentricity similar to that of humans and macaques, having roughly half the value of the human and with no clear departure for higher acuity in the periphery. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 300–313, 2017

Optogenetics has revolutionized the study of functional neuronal circuitry (Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K. Nat Neurosci 8: 1263–1268, 2005; Deisseroth K. Nat Methods 8: 26–29, 2011). Although these techniques have been most successfully implemented in rodent models, they have the potential to be similarly impactful in studies of nonhuman primate brains. Common marmosets (Callithrix jacchus) have recently emerged as a candidate primate model for gene editing, providing a potentially powerful model for studies of neural circuitry and disease in primates. The application of viral transduction methods in marmosets for identifying and manipulating neuronal circuitry is a crucial step in developing this species for neuroscience research. In the present study we developed a novel, chronic method to successfully induce rapid photostimulation in individual cortical neurons transduced by adeno-associated virus to express channelrhodopsin (ChR2) in awake marmosets. We found that large proportions of neurons could be effectively photoactivated following viral transduction and that this procedure could be repeated for several months. These data suggest that techniques for viral transduction and optical manipulation of neuronal populations are suitable for marmosets and can be combined with existing behavioral preparations in the species to elucidate the functional neural circuitry underlying perceptual and cognitive processes.

The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors.

The primate superior colliculus (SC) is important for the winner-take-all selection of targets for orienting movements. Such selection takes time, however, and the earliest motor responses typically are guided by a weighted vector average of the visual stimuli, before the winner-take-all selection of a single target. We tested whether SC activity plays a role in this initial stage of orienting by inactivating the SC in two macaques (Macaca mulatta) with local muscimol injections. After SC inactivation, initial orienting responses still followed a vector average, but the contribution of the visual stimulus inside the affected field was decreased, and the contribution of the stimulus outside the affected field was increased. These results demonstrate that the SC plays an important role in the weighted integration of visual signals for orienting, in addition to its role in the winner-take-all selection of the target.

In addition to its well-known role in the control of saccades, the primate superior colliculus (SC) has been implicated in the processes of target choice for overt orienting movements and for covert spatial attention. We focally inactivated the SC, by muscimol injection, while monkeys selected the target of a smooth pursuit, saccade, or button press response from two competing stimuli. The choice stimuli were placed so that one appeared within and the other appeared outside the affected visual field. SC inactivation biased the subject to choose stimuli out of the affected visual field for all three types of responses, although the effects on target choice were significantly smaller for button presses. Inactivation caused no changes in the selection of single stimuli within or out of the affected visual field, indicating the choice bias was not caused by deficits in response execution. The inactivation-induced bias for smooth pursuit and button press responses indicates SC activity is important for selecting the target, independent of any role in saccade preparation.

Markov chains (stochastic processes where probabilities are assigned based on the previous outcome) are commonly used to examine the transitions between behavioral states, such as those that occur during foraging or social interactions. However, relatively little is known about how well primates can incorporate knowledge about Markov chains into their behavior. Saccadic eye movements are an example of a simple behavior influenced by information about probability, and thus are good candidates for testing whether subjects can learn Markov chains. In addition, when investigating the influence of probability on saccade target selection, the use of Markov chains could provide an alternative method that avoids confounds present in other task designs. To investigate these possibilities, we evaluated human behavior on a task in which stimulus reward probabilities were assigned using a Markov chain. On each trial, the subject selected one of four identical stimuli by saccade; after selection, feedback indicated the rewarded stimulus. Each session consisted of 200–600 trials, and on some sessions, the reward magnitude varied. On sessions with a uniform reward, subjects (n = 6) learned to select stimuli at a frequency close to reward probability, which is similar to human behavior on matching or probability classification tasks. When informed that a Markov chain assigned reward probabilities, subjects (n = 3) learned to select the greatest reward probability more often, bringing them close to behavior that maximizes reward. On sessions where reward magnitude varied across stimuli, subjects (n = 6) demonstrated preferences for both greater reward probability and greater reward magnitude, resulting in a preference for greater expected value (the product of reward probability and magnitude). These results demonstrate that Markov chains can be used to dynamically assign probabilities that are rapidly exploited by human subjects during saccade target selection.