Search

Cues that signal the possibility of receiving an electric shock reliably induce defensive activation. To determine whether cues can also easily reverse defensive reactions, a threat reversal paradigm was developed in which a cue signaling threat of shock reversed its meaning across the course of the study. This allowed us to contrast defensive reactions to threat cues that became safe cues, with responses to cues that continued to signal threat or safety. Results showed that, when participants were instructed that a previously threatening cue now signaled safety, there was an immediate and complete attenuation of defensive reactions compared to threat cues that maintained their meaning. These findings highlight the role that language can play both in instantiating and attenuating defensive reactions, with implications for understanding emotion regulation, social communication, and clinical phenomena. [ABSTRACT FROM AUTHOR]

Human and non-human primates rely on the ability to perceive and interpret facial expressions to guide effective social interactions. The neuropeptide oxytocin (OT) has been shown to have a critical role in the perception of social cues, and in humans to increase the number of saccades to the eye region. To develop a useful primate model for the effects of OT on information processing, we investigated the influence of OT on gaze behavior during face processing in rhesus macaques. Forty-five minutes after a single intranasal dose of either 24IU OT or saline, monkeys completed a free-viewing task during which they viewed pictures of conspecifics displaying one of three facial expressions (neutral, open-mouth threat or bared-teeth) for 5 s. The monkey was free to explore the face on the screen while the pattern of eye movements was recorded. OT did not increase overall fixations to the face compared to saline. Rather, when monkeys freely viewed conspecific faces, OT increased fixations to the eye region relative to the mouth region. This effect of OT was particularly pronounced when face position on the screen was manipulated so that the eye region was not the first facial feature seen by the monkeys. Together these findings are consistent with prior evidence in humans that intranasal administration of OT specifically enhances visual attention to the eye region compared to other informative facial features, thus validating the use of non-human primates to mechanistically explore how OT modulates social information processing and behavior. [ABSTRACT FROM AUTHOR]

Models of visual emotional perception suggest a reentrant organization of the ventral visual system with the amygdala. Using focused functional magnetic resonance imaging in humans with a sampling rate of 100 ms, here we determine the relative timing of emotional discrimination in amygdala and ventral visual cortical structures during emotional perception. Results show that amygdala and infero-temporal visual cortex differentiate emotional from nonemotional scenes ∼1 s before extrastriate occipital cortex, whereas primary occipital cortex shows consistent activity across all scenes. This pattern of discrimination is consistent with a reentrant organization of emotional perception in visual processing, in which transaction between rostral ventral visual cortex and amygdala originates the identification of emotional relevance. [ABSTRACT FROM AUTHOR]

The ventral pallidum (VP) is critical for motivated behaviors. While contemporary work has begun to elucidate the functional diversity of VP neurons, the molecular heterogeneity underlying this functional diversity remains incompletely understood. We used single-nucleus RNA sequencing and in situ hybridization to define the transcriptional taxonomy of VP cell types in mice, macaques, and baboons. We found transcriptional conservation between all three species, within the broader neurochemical cell types. Unique dopaminoceptive and cholinergic subclusters were identified and conserved across both primate species but had no homolog in mice. This harmonized consensus VP cellular atlas will pave the way for understanding the structure and function of the VP and identified key neuropeptides, neurotransmitters, and neurotransmitter receptors that could be targeted within specific VP cell types for functional investigations. [ABSTRACT FROM AUTHOR]

The amygdaloid complex mediates learning, memory, and emotions. Understanding the cellular and anatomical features that are specialized in the amygdala of primates versus other vertebrates requires a systematic, anatomically-resolved molecular analysis of constituent cell populations. We analyzed five nuclear subdivisions of the primate amygdala with single-nucleus RNA sequencing in macaques, baboons, and humans to examine gene expression profiles for excitatory and inhibitory neurons and confirmed our results with single-molecule FISH analysis. We identified distinct subtypes of FOXP2 + interneurons in the intercalated cell masses and protein-kinase C-δ interneurons in the central nucleus. We also establish that glutamatergic, pyramidal-like neurons are transcriptionally specialized within the basal, lateral, or accessory basal nuclei. Understanding the molecular heterogeneity of anatomically-resolved amygdalar neuron types provides a cellular framework for improving existing models of how amygdalar neural circuits contribute to cognition and mental health in humans by using nonhuman primates as a translational bridge., Competing Interests: CONFLICT OF INTEREST No conflicts of interest to declare.

Intrinsic uncertainty in the reward environment requires the brain to run multiple models simultaneously to predict outcomes based on preceding cues or actions, commonly referred to as stimulus- and action-based learning. Ultimately, the brain also must adopt appropriate choice behavior using reliability of these models. Here, we combined multiple experimental and computational approaches to quantify concurrent learning in monkeys performing tasks with different levels of uncertainty about the model of the environment. By comparing behavior in control monkeys and monkeys with bilateral lesions to the amygdala or ventral striatum, we found evidence for dynamic, competitive interaction between stimulus-based and action-based learning, and for a distinct role of the amygdala. Specifically, we demonstrate that the amygdala adjusts the initial balance between the two learning systems, thereby altering the interaction between arbitration and learning that shapes the time course of both learning and choice behaviors. This novel role of the amygdala can account for existing contradictory observations and provides testable predictions for future studies into circuit-level mechanisms of flexible learning and choice under uncertainty.

Human and non-human primate data clearly implicate the dorsolateral prefrontal cortex (dlPFC) as critical for advanced cognitive functions 1,2 . It is thought that intracortical synaptic architectures within dlPFC are the integral neurobiological substrate that gives rise to these processes, including working memory, inferential reasoning, and decision-making 3-7 . In the prevailing model, each cortical column makes up one fundamental processing unit composed of dense intrinsic connectivity, conceptualized as the 'canonical' cortical microcircuit 3,8 . Each cortical microcircuit receives sensory and cognitive information from a variety of sources which are represented by sustained activity within the microcircuit, referred to as persistent or recurrent activity 4,9 . Via recurrent connections within the microcircuit, activity can propagate for a variable length of time, thereby allowing temporary storage and computations to occur locally before ultimately passing a transformed representation to a downstream output 4,5,10 . Competing theories regarding how microcircuit activity is coordinated have proven difficult to reconcile in vivo where intercortical and intracortical computations cannot be fully dissociated 5,9,11,12 . Here, we interrogated the intrinsic features of isolated microcircuit networks using high-density calcium imaging of macaque dlPFC ex vivo . We found that spontaneous activity is intrinsically maintained by microcircuit architecture, persisting at a high rate in the absence of extrinsic connections. Further, using perisulcal stimulation to evoke persistent activity in deep layers, we found that activity propagates through stochastically assembled intracortical networks, creating predictable population-level events from largely non-overlapping ensembles. Microcircuit excitability covaried with individual cognitive performance, thus anchoring heuristic models of abstract cortical functions within quantifiable constraints imposed by the underlying synaptic architecture.

Genetically encoded synthetic receptors, such as the chemogenetic and optogenetic proteins, are powerful tools for functional brain studies in animals. In the primate brain, with its comparatively large, intricate anatomical structures, it can be challenging to express transgenes, such as the hM4Di chemogenetic receptor, in a defined anatomical structure with high penetrance. Here, we compare parameters for lentivirus vector injections in the rhesus monkey amygdala. We find that four injections of 20 μl, infused at 0.5 μl/min, can achieve neuronal hM4Di expression in 50-100% of neurons within a 60 mm 3 volume, without observable damage from overexpression. Increasing the number of hM4Di_CFP lentivirus injections to up to 12 sites per hemisphere, resulted in 30%-40% neuronal coverage of the overall amygdala volume, with coverage reaching 60% in some subnuclei. Manganese Chloride was mixed with lentivirus and used as an MRI marker to verify targeting accuracy and correct unsuccessful injections in these experiments. In a separate monkey we visualized, in vivo , viral expression of the hM4Di receptor protein in the amygdala, using Positron Emission Tomography. Together, these data show efficient and verifiable expression of a chemogenetic receptor in old-world monkey amygdala., Competing Interests: None., (© 2023 The Authors. Published by Elsevier B.V.)