Critically, there was a selective decrease in somatostatin-positive interneuron density in the stratum oriens layer of CA3 (Fig. Older monkeys were impaired relative to adults on some, but not all, of the cognitive functions tested in the battery, indicating that distinct aspects of cognition operate partially independent of one another in aged macaques, as is the case in older humans (91⇓⇓⇓–95). NAS colloquia began in 1991 and have been published in PNAS since 1995. Biomedical communities and journals need to standardize nomenclature of gene products to enhance accuracy in scientific and public communication. As a result, histological experiments aimed at quantifying the number of neurons expressing calcium binding proteins (CaBPs) were conducted throughout the central auditory system. (A) Proportion of correct responses made by adult and aged rhesus macaques performing a delayed nonmatching-to-sample task at different delays. Nobody likes the idea of experimenting on animals. In fact, the density of CaBP-expressing neurons has been found to be significantly associated with higher acoustic thresholds and fewer inner and outer hair cells at the level of the cochlea in macaques (58, 59, 65) (Fig. These characteristics allow different aspects of brain function to be tested with similar or even identical tests as those used in humans. The present review will highlight how nonhuman primates provide a critical bridge between experiments conducted in rodents and development of therapeutics for humans. Additionally, fewer somatostatin-positive interneurons and higher CA3 firing rates were associated with poorer cognition (Fig. We present evidence for continuous generation of neurons, oligodendrocytes, and astrocytes in the hippocampal dentate gyrus of adult macaque monkeys, using immunohistochemical double labeling for bromodeoxyuridine and cell-type-specific markers. George is a senior staff reporter at Gizmodo. An absolute must for all neuroscientists navigating the rhesus monkey brain."--Dr. 3 B–D). What’s more, the findings could take us closer to understanding consciousness itself. Image credit: Shutterstock/greenbutterfly. That said, the scientists used a dozen ceramic skull screws and dental acrylic to “affix head implants” on the monkeys, among other severely invasive measures required for the experiment, some of which were designed to immobilize the heads of the monkeys during EEG readings. The calcium hypothesis of brain aging posits that excess intracellular calcium levels in aging hippocampal cells result in altered cellular metabolism, gene expression, and neurotransmitter release that may ultimately result in mnemonic impairment (18, 23, 24). Non-human primates like the macaque are able to communicate about such things as food, identity or danger with vocalizations that are interpreted by others of their species and acted upon. The authors declare no conflict of interest. These anatomical differences between species are thought to reflect the drastically different acoustic sensitivities of primates and rodents. 1). E.A.B. The data discussed here do not focus on age-associated changes in the cochlea, but rather on the central auditory system’s response to a weakened drive from the periphery. In particular, superior auditory processing was associated with better performance on tests of concurrent reversal learning, object recognition memory, and discrimination of objects with high feature overlap, but not with performance on tests of reward devaluation, spatial short-term memory, or object discrimination. Here we report techniques for long-term two-photon imaging in awake macaque monkeys. The rich literature in histological connectivity analysis studies in the macaque monkey enables quantitative evaluation of the performance of tractography algorithms. Baseline firing rates were significantly greater in the CA3 of aged animals relative to the adults. It becomes especially critical to use animal models that possess brains with chemical compositions similar to those of humans when potential therapies depend on targeting genetically defined cell types. D, dorsal; L, lateral; M, medial; V, ventral. I mean, side-effects aside, of course. 59, which is published under CC BY 3.0. The brain of four adult male Rhesus macaque monkeys (Macaca mulatta, M1-4) (~10–15 y old,~9 kg) were used in this study. This might be achieved either by finding a means to abolish hyperexcitability or by enhancing built-in cellular mechanisms that aged auditory neurons appear to employ to help maintain a healthier intracellular state in the face of pathophysiology elsewhere in the system. Functional anatomical work has shown that neurons belonging to each pathway participate in vastly different aspects of acoustic processing, with the parvalbumin-rich direct pathway primarily acting as an information-relay system and the calbindin-rich indirect pathway acting more as a modulator (68). Consistent with this prediction, normalizing excess neural activity in human participants using an anticonvulsant medication does partially rescue cognitive performance in patients with mild cognitive impairment (26). I’d absolutely be down for a brain implant that I could switch myself off like a light by stimulating the thalamus at a different frequency, then waking myself up. It seems like the definition of inhumanity,…. SOM interneuron densities were reduced in the stratum oriens layer of CA3 in aged animals, but not in the stratum radiatum or in the PRC. Note the qualitatively greater density of parvalbumin-positive cells in the older animal. Recent public concern about nonhuman primate research has made it imperative to attempt to clearly articulate the potential benefits to human health that this model enables. The study was conducted in macaque monkeys. First, monkeys possess cognitive and sensory repertoires that more closely resemble those of humans compared with other animal models (7). Macaque brain. Reprinted with permission from refs. A critical aspect of the experiment was to correctly evaluate wakefulness in the two monkeys used in the experiment, dubbed Monkey R and Monkey W. “We modeled our assessment of wakefulness in monkeys on clinical measures that are used to assess coma patients or patients that are undergoing anesthesia,” Redinbaugh told Gizmodo. Source memory in older adults: An encoding or retrieval problem? Schematic depiction of the relative size of auditory nuclei within the SOC of humans, macaques, and rats. Consequently, age-related deficits in human episodic memory are thought to largely result from structural and functional alterations in these structures, although the precise neurobiological mechanisms involved have been difficult to pinpoint. One often misunderstood aspect of the normative brain aging process is that while an enormous absolute number of individuals present with a dementing neurodegenerative disease at some time in their life (14% of people over the age of 70 y), the vast majority of people (86%) take healthier cognitive trajectories (2). Jaan Aru, a neuroscientist at Humboldt University in Berlin, said researchers in the 1990s began to think that the thalamus was important for consciousness—a belief predicated on the fact that the thalamus is located in a central position for control and that it can change how other brain regions process information. Animals were euthanized first by sedation using ketamine and dexdomitor, followed by deep anesthetization using pentobarbital and phenytoin, and then were perfused transcardially with 4% (wt/vol) paraformaldehyde in phosphate buffer. The basic laminar organization of excitatory local circuitry in the primary visual cortex of the macaque monkey is similar to that described previously in the cat's visual cortex . Critically, rodents do not appear to have these chemically defined parallel auditory pathways since the auditory thalamus of rats is almost completely devoid of parvalbumin and lacks calbindin in many areas where it is clearly expressed in primates (69, 70). Emergence of a powerful connection between sensory and cognitive functions across the adult life span: A new window to the study of cognitive aging? The brain was removed, and cortex was separated from subcortical structures and cryoprotected in 30% sucrose. In this study, we applied both histone demethylase Kdm4d mRNA and histone deacetylase inhibitor trichostatin A (TSA) to the cloning of macaque monkeys. When contemplating the coos and screams of a fellow member of its species, the macaque uses brain regions that correspond to the two principal language centers in the human brain. Shutterstock / Blueton. Face recognition and the interpretation of facial expressions and gaze direction play a key role in guiding the social behavior of human beings, and new study results point to similar mechanisms in macaques. “This study is significant,” said Earl Miller, a professor of neuroscience from the Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology, in an email to Gizmodo. Neuroscientists had previously pegged the central lateral thalamus as an NCC, but this latest research adds more credence to the claim. “This study puts thalamus back to the picture,” Aru, who is not affiliated with the new study, told Gizmodo. Furthermore, given the rich literature base on cognitive and sensory aging in the macaque that does not yet exist in the marmoset, combined with major advances in fast gene-editing technologies such as the CRISPR/Cas9 system (103), a parallel approach may be to expand the suite of tools available in the marmoset to macaques in order to take advantage of these past advances. 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Finally, animal models help control for generational effects that sometimes influence human aging research (6) since young and aged animals can be exposed to similar testing and living conditions over the course of their lifespans. Materials and Methods. Regardless, there was a strong negative correlation between the density of somatostatin-positive CA3 interneurons and principal neuron firing rates (Fig. A rhesus macaque. This article is a PNAS Direct Submission. We do not capture any email address. Comparison of human, macaque, and mouse brains. Lewis, J.W., Van Essen, D.C.: Corticocortical connections of visual, sensorimotor, and multimodal processing areas in the parietal lobe of the macaque monkey. 2018-06: Visualize your own data inside a brain atlas with SBA Composer. Preserved specimen of the brain of a long-tailed macaque (Macaca fascicularis). From February 2001 through May 2019 colloquia were supported by a generous gift from The Dame Jillian and Dr. Arthur M. Sackler Foundation for the Arts, Sciences, & Humanities, in memory of Dame Sackler's husband, Arthur M. Sackler. Unfortunately, public awareness of the importance of nonhuman primates in neuroscience research as a whole, and their importance in aging research in particular, is limited. Adapted by permission from ref. Conversely, parvalbumin-positive interneuron numbers did not change with age, and they were not associated with firing rates or object recognition memory abilities. … Reprinted with permission from ref. This paper results from the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Using Monkey Models to Understand and Develop Treatments for Human Brain Disorders,” held January 7–8, 2019, at the Arnold and Mabel Beckman Center of the National Academies of Sciences and Engineering in Irvine, CA. Whether the reduction observed reflects cellular degeneration or a biochemical down-regulation of the neuropeptide somatostatin remains an open question. Unlike in the prefrontal cortex, the density of axospinous synapses, which are the predominant synapse type in the dentate gyrus, remains stable across the macaque lifespan (39, 40). 2C). To do so, they designed a stimulation method that mimicked the way brain cells act in the central lateral thalamus during the waking state. Adult and aged macaques completed a battery of behavioral tests designed to probe the function of distinct aspects of frontal and temporal lobe-dependent cognition. The anterior insular cortex is a small brain region that plays a crucial role in human self-awareness and in related neuropsychiatric disorders. 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These observations indicate that neurochemical changes occur within the central auditory system in response to a reduced acoustic drive from the periphery. The older animals were shown to be significantly impaired relative to the younger animals (Fig. CRISPR-Cas9 gene editing can improve the effectiveness of spermatogonial stem cell transplantation in mice and livestock, a study finds. During the experiments, for example, a clinical anesthesiologist was to present to make sure the monkeys “received the same level of care as human patients in the hospital,” said Redinbaugh, and the animals were monitored both during and after the experiments to “ensure their health and wellbeing,” among other measures, she said. Recordings obtained from awake-behaving dorsolateral prefrontal cortex are inconsistent with these findings in that the firing rates in older monkeys performing a spatial working memory task have been observed to be reduced (42). The calcium hypothesis suggests that rebalancing intracellular calcium levels, and perhaps hyperexcitability, by increasing inhibition to control excess neural activity may rebalance circuit activity and help preserve memory function in aging. Distinguishing similar, but nonidentical, experiences is a critical aspect of episodic memory that commonly becomes impaired in older individuals (16). Finally, another possibility is that the extent of neuronal connectivity between regions may determine the degree to which brain functions covary across the lifespan through mechanisms associated with hyperexcitability or changes in synaptic function. Macaque Monkey is a YouTube channel that upload everyday about MONKEY. Three rhesus macaques (1 male, 2 females, 4–6 kg, 8–9 years of age) were tested. Diffusion tensor … “Thousands of people are given general anesthesia each year. This fascinating result is providing new clues about the brain and how it produces conscious awareness—insights that could potentially lead to therapies for patients trapped in a coma. The SOC is the first site of binaural integration in the auditory system, and is critical in computing the interaural time, intensity, and phase differences necessary for sound source localization in azimuth (72, 73). Some species, such as the crab-eating macaque, subsist on a diet of invertebrates and occasionally small vertebrates. Each voxel in the atlas is a cube 150 um on a side. Understanding the primate brain at a similar level of detail is facilitated by optogenetics in the macaque monkey—a model organism with a brain structure similar to humans that can be trained to perform complex behavioral tasks. The technology could one day make artificial eyesight possible in humans. 58; and 59, which is published under CC BY 3.0. Furthermore, these electrophysiological changes were significantly associated with performance on an object recognition task (41). The brains of the monkeys are considered a delicacy, and they are thought to be a cure for impotence. This is largely due to the availability of technologies in animals that provide a means of dissecting neuronal circuits with superior temporal, spatial, and genetic precision than is possible in humans. Since the 2000s, however, neuroscientists have focused primarily on the cortex to find the mechanisms of consciousness, he said. 104. Among others, 2 differences will be discussed here: 1) distinct CaBP expression patterns of auditory neurons and 2) distinct hearing ranges between rodents and macaques. Hippocampal synapse density has also been carefully examined across the macaque lifespan, with the bulk of this work focusing on synapses formed by perforant path input from the superficial layers of the entorhinal cortex to the inner and outer molecular layers of the dentate gyrus (38). This circuitry is described here in the context of a two-level model that distinguishes between feedforward and feedback connections. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. Because the impact that age will have on a specific neural network cannot necessarily be predicted a priori, it is essential to examine regions independently as age-related changes in one circuit may not generalize to those observed in another. Note that lower values indicate better function for both auditory measures. Together, these observations indicate that auditory processing abilities functionally covary specifically with aspects of cognition driven by medial temporal lobe networks, regardless of auditory acuity. Because cognitive problems arise relatively late in the progression of these diseases, some participants considered to be aging normally may actually have undetected pathophysiological brain markers during the period when behavioral testing is conducted (5). Additionally, the shape and organization of the other olivary nuclei are very different in the rat compared with monkeys and humans. Hearing impairment and incident dementia and cognitive decline in older adults: The health ABC study, Hearing loss and cognition among older adults in the United States, Hearing loss in older adults affects neural systems supporting speech comprehension, Neural processing during older adults’ comprehension of spoken sentences: age differences in resource allocation and connectivity, Functional changes in the human auditory cortex in ageing, Language and the aging brain: Patterns of neural compensation revealed by functional brain imaging. For example, a generational effect sometimes encountered in human cognitive neuroscience is differential exposure to technology, such as expertise with computers, between generations that can cause older individuals to perform more poorly than younger people on tasks, regardless of their actual cognitive status (6). and C.A.B. For … With respect specifically to a calcium homeostasis approach, there is evidence that CaBP expression differs considerably between the auditory systems of primates and rodents. On average, southern pig-tailed macaques in Malaysia eat about 70 large rats each per Over the past several decades, neuroscientists have teased apart the various regions and networks in the brain to better understand how they contribute to normal cognitive function, but huge questions remain about consciousness and which parts of the brain can be described as the neural correlates of consciousness (NCCs)—that is, the specific brain regions that allow us to experience the smell of burnt toast, the redness of a blooming rose, or the richness of our internal thoughts. Aged animals were significantly impaired relative to adult animals at the 600-s delay condition. Diffusion tensor imaging analyses of frontal cortex- and medial temporal lobe-associated white matter microstructural condition were performed in the same monkeys to determine whether sensory and cognitive processing abilities are associated with the structural composition of these cognitive circuits. (D) Representative probability map of the right hemisphere frontal thalamic radiation overlaid upon T1-weighted MRI (Top) and an FA map pseudocolored in copper (Bottom). The ability to uncover the neurobiological changes responsible for dementing neurodegenerative disease requires knowledge of the “normal” trajectory that brain function takes across the lifespan. More recently, the impact that hearing loss, in particular, has on cognition has reemerged as a topic of research interest. Localization of higher frequency sounds occurs primarily through interaural intensity difference calculations in the lateral superior olivary (LSO) nucleus (74⇓⇓⇓–78). Using electrode arrays, the scientists were able to record brain activity from multiple brain areas, allowing them to monitor consciousness in the macaques while they were awake, sleeping, and under anesthesia. This similarity in cortical function between humans and old-world monkeys suggests that brain networks supporting volitional communication have a common evolutionary origin that arose well prior to the hominin radiation. Based on acoustic sensitivity, the auditory system of mice should utilize calculations of interaural intensity differences in the LSO more so than the primate auditory system, which should utilize interaural time difference calculations in the MSO to a greater extent. Stimulating this small brain region, which is located deep in the forebrain, caused anesthetized monkeys to suddenly wake up and be alert, despite the fact that anesthetic drugs were still being administered. In support of this idea, there is evidence that occlusions of distinct cerebral arteries result in different patterns of cognitive dysfunction, indicating that there is some level of regional specificity in the impact of a given vascular insult (98). 2018-05: After 9 years of operation, ran broken link detector on the Scalable Brain Atlas ecosystem and fixed 40 issues. Reproduced with permission from ref. Interaural time differences are the primary cue used to localize lower frequency sounds, and these computations primarily involve the medial superior olivary (MSO) nucleus (74, 75). In terms of the ethics involved, “University of Wisconsin-Madison Institutional Animal Care and Use Committee approved all procedures, which conformed to the National Institutes of Health Guide for the Care and Use of Laboratory Animals,” the authors wrote in the paper. Reproduced with permission from ref. Little Dog claims that the brain of a macaque monkey is closer to a human brain than any other living mammal, and he claims that the macaques are capable of critical thought and problem solving, and that they have the ability to recall past events. (A) Images of the dorsal surface of a human brain, macaque brain, and mouse brain. Conversely, the domestic mouse cannot hear 60-dB tones below 2.3 kHz and can hear up to 85.5 kHz (71). This suggests that the relationships between the fractional anisotropy of hippocampus-associated white matter tracts and hearing function were not due to general changes in white matter systems across the aging brain. (D) CA3 SOM neuron densities were significantly negatively correlated with CA3 baseline firing rates. Recent work utilizing aging macaques provides a perspective on the association between auditory and cognitive function across the lifespan (90). One location along the ascending auditory pathway where these interspecies differences are clear is within the superior olivary complex (SOC) in the ventral brainstem. Importantly, the number of a specific type of interneuron expressing the neuropeptide somatostatin was positively associated with memory function in aged rats (25). Shapeshifting designs could have wide-ranging pharmaceutical and biomedical applications in coming years. and by the McKnight Brain Research Foundation. 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