Rafael S. Maior

Pulvinar neurons reveal neurobiological evidence of past selection for rapid detection of snakes

Significance The present study shows preferential activity of neurons in the medial and dorsolateral pulvinar to images of snakes. Pulvinar neurons responded faster and stronger to snake stimuli than to monkey faces, monkey hands, and geometric shapes, and were sensitive to unmodified and low-pass filtered images but not to high-pass filtered images. These results identify a neurobiological substrate for rapid detection of threatening visual stimuli in primates. Our findings are unique in providing neuroscientific evidence in support of the Snake Detection Theory, which posits that the threat of snakes strongly influenced the evolution of the primate brain. This finding may have great impact on our understanding of the evolution of primates. Snakes and their relationships with humans and other primates have attracted broad attention from multiple fields of study, but not, surprisingly, from neuroscience, despite the involvement of the visual system and strong behavioral and physiological evidence that humans and other primates can detect snakes faster than innocuous objects. Here, we report the existence of neurons in the primate medial and dorsolateral pulvinar that respond selectively to visual images of snakes. Compared with three other categories of stimuli (monkey faces, monkey hands, and geometrical shapes), snakes elicited the strongest, fastest responses, and the responses were not reduced by low spatial filtering. These findings integrate neuroscience with evolutionary biology, anthropology, psychology, herpetology, and primatology by identifying a neurobiological basis for primates’ heightened visual sensitivity to snakes, and adding a crucial component to the growing evolutionary perspective that snakes have long shaped our primate lineage.

Predatory stress as an experimental strategy to measure fear and anxiety-related behaviors in non-human primates.

Natural defense-inducing stimuli are being increasingly exploited as a means to investigate the neural mechanisms underlying normal and pathological anxiety, as well as for the screening of new compounds with potential therapeutic use in human anxiety disorders. Such an approach, frequently used in rodents, has recently been employed in the Marmoset Predator Confrontation Test (MPCT). In this method, marmoset monkeys are individually confronted with a taxidermized predator (wild oncilla cat) in a previously habituated maze environment, while several easily discernable fear/anxiety-related behaviors are measured. Confrontation with the cat stimulus significantly altered ongoing behaviors, each habituating distinctively during repeated exposures; e.g. complete rapid habituation (alarm call), complete slow habituation (exploration, vigilance) or only partial habituation (proximity avoidance). Pharmacological validating studies with diazepam and buspirone induced a significant dose-dependent reversal of the fear-induced proximic avoidance and scratching/scent-marking behaviors, while exploration (smell/lick the maze, leg stand) was found to increase. The neuropeptide substance P and the selective 5-HT1A receptor antagonist WAY100635 resulted in a similar anxiolytic-like profile. The response pattern observed was not influenced by social isolation, handling/manual restraint, novel environment exposure or habituation to the stimulus or its location. Persistent defensive behavior and response pattern to diazepam was observed when naive versus MPCT-experienced marmosets were tested following a recent predatory stress. Taken together, the results indicate that the MPCT is a valuable experimental procedure to measure fear and anxiety-related behaviors in nonhuman primates.

Neuronal responses to face-like and facial stimuli in the monkey superior colliculus.

The superficial layers of the superior colliculus (sSC) appear to function as a subcortical visual pathway that bypasses the striate cortex for the rapid processing of coarse facial information. We investigated the responses of neurons in the monkey sSC during a delayed non-matching-to-sample (DNMS) task in which monkeys were required to discriminate among five categories of visual stimuli [photos of faces with different gaze directions, line drawings of faces, face-like patterns (three dark blobs on a bright oval), eye-like patterns, and simple geometric patterns]. Of the 605 sSC neurons recorded, 216 neurons responded to the visual stimuli. Among the stimuli, face-like patterns elicited responses with the shortest latencies. Low-pass filtering of the images did not influence the responses. However, scrambling of the images increased the responses in the late phase, and this was consistent with a feedback influence from upstream areas. A multidimensional scaling (MDS) analysis of the population data indicated that the sSC neurons could separately encode face-like patterns during the first 25-ms period after stimulus onset, and stimulus categorization developed in the next three 25-ms periods. The amount of stimulus information conveyed by the sSC neurons and the number of stimulus-differentiating neurons were consistently higher during the 2nd to 4th 25-ms periods than during the first 25-ms period. These results suggested that population activity of the sSC neurons preferentially filtered face-like patterns with short latencies to allow for the rapid processing of coarse facial information and developed categorization of the stimuli in later phases through feedback from upstream areas.

Decreased methylation of the NK3 receptor coding gene (TACR3) after cocaine-induced place preference in marmoset monkeys

Epigenetic processes have been implicated in neuronal plasticity following repeated cocaine application. Here we measured DNA methylation at promoter CpG sites of the dopamine transporter (DAT1) and serotonin transporter (SERT) and neurokinin3‐receptor (NK3‐R)‐receptor (TACR3) coding genes in marmoset monkeys after repeated cocaine injections in a conditioned place preference paradigm. We found a decrease in DNA methylation at a specific CpG site in TACR3, but not DAT1 or SERT. Thus, TACR3 is a locus for DNA methylation changes in response to repeated cocaine administration and its establishment as a reinforcer, in support of other evidence implicating the NK3‐R in reinforcement‐ and addiction‐related processes.

Superior colliculus lesions impair threat responsiveness in infant capuchin monkeys.

The ability to react fast and efficiently in threatening situations is paramount for the survival of organisms and has been decisive in our evolutionary history. Defense mechanisms in primates rely on the fast recognition of potential predators and facial expressions of conspecifics. The neural circuitry responsible for the detection of threat is generally thought to be centered on the amygdala. Although it is a pivotal structure in the processing of emotional stimuli, the amygdala does not seem necessary for the early stages of this process. Here we show that bilateral neurotoxic lesions of the superior colliculus in infant capuchins monkeys impaired the recognition of a rubber-snake in a threat-reward conflict task. Lesioned monkeys were uninhibited by a snake in a food-reward retrieval task. Lack of inhibition in the task was observed over the course of 15 weeks. The long lasting recognition impairment of a natural predator observed here is similar to the tameness aspects of Kluver-Bucy syndrome, indicating an important role of this structure in threat recognition.

Neural correlates to seen gaze-direction and head orientation in the macaque monkey amygdala.

Human neuropsychological studies suggest that the amygdala is implicated in social cognition, in which cognition of seen gaze-direction, especially the direct gaze, is essential, and that the perception of gaze direction is modulated by the head orientation of the facial stimuli. However, neural correlates to these issues remain unknown. In the present study, neuronal activity was recorded from the macaque monkey amygdala during performance of a sequential delayed non-matching-to-sample task based on gaze direction. The facial stimuli consisted of two head orientations (frontal; straight to the monkey, profile; 30 degrees rightwards from the front) with different gaze directions (directed toward and averted to the left or right of the monkey). Of the 1091 neurons recorded, 61 responded to more than one facial stimulus. Of these face-responsive neurons, 44 displayed responses selective to the facial stimuli (face neurons). Most amygdalar face neurons discriminated both gaze direction and head orientation, and exhibited a significant interaction between the two types about information. Furthermore, factor analysis on the response magnitudes of the face neurons to the facial stimuli revealed that two factors derived from these facial stimuli were correlated with two head orientations. The overall responses of the face neurons to direct gazes in the profile and frontal faces were significantly larger than that to averted gazes. The results suggest that information of both gaze and head direction is integrated in the amygdala, and that the amygdala is implicated in detection of direct gaze.

Interaction of the tachykinin NK3 receptor agonist senktide with behavioral effects of cocaine in marmosets (Callithrix penicillata)

Brain neuropeptide transmitters of the tachykinin family are involved in the organization of many behaviors. However, little is known about their contribution to the behavioral effects of drugs of abuse. Recently, antagonism of the tachykinin NK3-receptor (NK3-R), one of the three tachykinin receptors in the brain, was shown to attenuate the acute and chronic behavioral effects of cocaine in rats and the acute effects in non-human primates. In order to expand these findings we investigated the effects of the NK3-R agonist, succinyl-[Asp6, Me-Phe8]SP(6-11) (senktide), on the acute behavioral effects of cocaine in marmoset monkeys (Callithrix penicillata) using a figure-eight maze procedure. Animals were pretreated with senktide (0, 0.1, 0.2, 0.4 mg/kg, s.c.), and received either a treatment with cocaine (10 mg/kg) or saline (i.p.). Cocaine increased locomotor activity and the duration of aerial scanning behavior, but reduced exploratory activity, bodycare activity, the frequency of aerial scanning, and terrestrial glance behavior. Senktide blocked the effects of cocaine on locomotor activity, but enhanced the cocaine effects on exploratory activity, aerial scanning frequency, and terrestrial glance behavior. Senktide alone did not significantly influence monkey behavior in this study. These data expand previous findings suggesting a complex role of the NK3-R in the acute behavioral effects of cocaine in non-human primates.

A role for the superior colliculus in the modulation of threat responsiveness in primates: toward the ontogenesis of the social brain.

Abstract Defense and social mechanisms in primates seem to share, at least in infancy, common neural substrata. Among these, recent research has implicated the primate superior colliculus (SC) on tasks involving visual detection and recognition of threatening stimuli, such as snakes and faces with emotional expressions. There is also evidence that both kinds of stimuli share specific characteristics and command special attention in the primate visual system. The present review focuses on the role of the SC in these seemingly overlapping functions. We present social behavioral data from capuchin monkeys in which the bilateral lesion of the SC induced a transitory impairment of social behaviors. The findings presented here are compared with previous studies, our own and others, on social behaviors and threat detection. We argue that, although the SC may participate in both systems, its role is more prominent in the detection/recognition of threat. Social interactions more likely depend on larger and more complex neural systems, where the SC may play a key role in early infancy. The implications of these recent findings are discussed under an evolutionary perspective.

Fast detector/first responder : interactions between the superior colliculus-pulvinar pathway and stimuli relevant to primates

Primates are distinguished from other mammals by their heavy reliance on the visual sense, which occurred as a result of natural selection continually favoring those individuals whose visual systems were more responsive to challenges in the natural world. Here we describe two independent but also interrelated visual systems, one cortical and the other subcortical, both of which have been modified and expanded in primates for different functions. Available evidence suggests that while the cortical visual system mainly functions to give primates the ability to assess and adjust to fluid social and ecological environments, the subcortical visual system appears to function as a rapid detector and first responder when time is of the essence, i.e., when survival requires very quick action. We focus here on the subcortical visual system with a review of behavioral and neurophysiological evidence that demonstrates its sensitivity to particular, often emotionally charged, ecological and social stimuli, i.e., snakes and fearful and aggressive facial expressions in conspecifics. We also review the literature on subcortical involvement during another, less emotional, situation that requires rapid detection and response—visually guided reaching and grasping during locomotion—to further emphasize our argument that the subcortical visual system evolved as a rapid detector/first responder, a function that remains in place today. Finally, we argue that investigating deficits in this subcortical system may provide greater understanding of Parkinsons disease and Autism Spectrum disorders (ASD).

Snakes elicit earlier, and monkey faces, later, gamma oscillations in macaque pulvinar neurons

Gamma oscillations (30–80 Hz) have been suggested to be involved in feedforward visual information processing, and might play an important role in detecting snakes as predators of primates. In the present study, we analyzed gamma oscillations of pulvinar neurons in the monkeys during a delayed non-matching to sample task, in which monkeys were required to discriminate 4 categories of visual stimuli (snakes, monkey faces, monkey hands and simple geometrical patterns). Gamma oscillations of pulvinar neuronal activity were analyzed in three phases around the stimulus onset (Pre-stimulus: 500 ms before stimulus onset; Early: 0–200 ms after stimulus onset; and Late: 300–500 ms after stimulus onset). The results showed significant increases in mean strength of gamma oscillations in the Early phase for snakes and the Late phase for monkey faces, but no significant differences in ratios and frequencies of gamma oscillations among the 3 phases. The different periods of stronger gamma oscillations provide neurophysiological evidence that is consistent with other studies indicating that primates can detect snakes very rapidly and also cue in to faces for information. Our results are suggestive of different roles of gamma oscillations in the pulvinar: feedforward processing for images of snakes and cortico-pulvinar-cortical integration for images of faces.