A few functional imaging studies in older humans have shown compensatory recruitment of certain auditory, frontal, and temporoparietal brain regions when older people listen to human speech, even in subjects with clinically normal hearing thresholds (85⇓⇓⇓–89). Brain stimulation device lets monkeys 'see' shapes without using eyes. To do so, they designed a stimulation method that mimicked the way brain cells act in the central lateral thalamus during the waking state. Animals. Examining the relationship between auditory function and cognitive decline in aging macaque monkeys, PhD dissertation, The University of Arizona, Tucson, AZ (2019). (C) Magnified images of CA3 and PRC SOM inhibitory neurons. The results discussed here call for a shift in focus in cognitive aging research toward understanding how different brain functions impact one another across a lifespan. We thank Michelle Albert for assistance with the graphics. 2C). In awake macaques, prefrontal cortical neurons show reduced firing rates (42), whereas temporal lobe neurons recorded in the CA3 region show increased excitability (27), but hippocampal granule cells recorded in vitro show no change in firing rate (43). The brain remains the most mysterious organ in the human body. 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. Both of these points emphasize how nonhuman primates can provide a fundamental link between nonprimate laboratory animals and humans. Michelle Redinbaugh, the first author of the new study and a graduate student at the University of Wisconsin-Madison, said the primary goal of the experiment was to locate NCCs in the brain. What that in mind, the new research could result in effective new therapies to treat disorders of consciousness, improved deep brain stimulation as a surgical technique, and better drugs for anesthesia. These data also provide a possible mechanistic explanation for the excitability observed at the single-cell level in aged rats and in fMRI studies in older humans. This circuitry is described here in the context of a two-level model that distinguishes between feedforward and feedback connections. What’s more, the findings could take us closer to understanding consciousness itself. 104. Macaque monkeys, in particular, have been the predominant nonhuman primate model in neuroscience, although relatively recent advances in transgenic technologies for use in marmosets (99⇓–101) have rapidly established this anthropoid as a promising additional nonhuman primate tool. Adult and aged monkeys underwent a test of object recognition memory. 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. Interspecies differences in the chemical composition of different brain regions highlight that not all aspects of brain physiology are the same across species. (Bottom) Rats, on the other hand, have a drastically expanded LSO relative to humans and macaques, as well as a significantly reduced MSO. 2A). Animal models of cognitive and sensory aging have enriched our understanding of the mechanisms that contribute to different aspects of healthy brain aging. Audiometric deficits can result from various insults to the cochlea that diminish this sensory organ’s capacity to transduce acoustic information (44⇓⇓–47). Insights into these basic questions are critical for devising strategies to maintain cognitive health in older individuals who fall along all points of the sensory and cognitive aging spectrum. (B) Boxplots of pyramidal neuron baseline firing rates recorded from the perirhinal cortex (PRC) and CA3 in adult and aged monkeys. 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. By prodding a tiny brain region linked to consciousness, scientists caused anesthetized monkeys to suddenly become awake and alert. While fMRI technologies can detect broad changes in activity, they do not provide detailed circuit-level insights into such changes. 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 . These observations indicate that the neurobiological processes driving functional changes in aged cognitive circuits (e.g., hyperexcitability) likely occur at subcellular levels. In short, Little Dog says, macaque monkeys “employ memory … Baseline firing rates were significantly greater in the CA3 of aged animals relative to the adults. Copyright © 2021 National Academy of Sciences. 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). Our purpose is to bring all daily monkey activities such as monkey giving birth, cute baby monkeys, monkey playing etc . Embedded within this basic framework is a more complex organization. Nobody likes the idea of experimenting on animals. These observations indicate that the brains of older people functionally reorganize themselves to preserve auditory perception. Under this hypothesis, the efficacy of neural circuits in relatively close proximity might become similarly impacted by vascular aging. Baseline firing rates were significantly higher in the CA3 region, but not in the perirhinal cortex, of the older monkeys compared with the adults, consistent with the regional specificity of the age-associated hyperactivity observed in aged humans (Fig. 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. 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. 2E). 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). (Scale bar, 100 μm.) 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). This finding indicates a cross-species similarity in this age-associated hyperexcitability between rats and humans (15, 16). Leslie G. Ungerleider, NIMH-NIH "This is an extraordinarily detailed and comprehensive atlas of the macaque monkey brain. Second, differential patterns of age-related neurovascular dysfunction between different brain regions also could bias circuits contained within a lobe to experience comparable physiological consequences associated with poorer vascular health. Visual information processing and auditory thresholds were not associated with any aspect of cognition tested. The scientists also monitored their EEG responses to both common and unusual sounds, “which can distinguish consciousness from unconscious subjects,” she added. The 23 species of macaques inhabit ranges throughout Asia, North Africa, and Gibraltar. 2D). and C.A.B. Once the stimulation was turned off, the macaques returned to an unconscious state. Adapted by permission from ref. Brain atlases, and particularly those based on magnetic resonance imaging (MRI), have become important tools for understanding normal brain structure, and for identifying structural abnormalities resulting from disease states, exposures, and/or aging. Recent work utilizing aging macaques provides a perspective on the association between auditory and cognitive function across the lifespan ( 90 ). (B) Age is significantly associated with greater numbers of auditory neurons expressing parvalbumin in the core of the inferior colliculus (IC). Monkeys with greater fractional anisotropy in the fimbria-fornix (Fig. A major goal within the field of the neuroscience of aging is to determine what factors allow certain individuals to evade neurodegenerative disease, while others succumb to them. 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). The rhesus macaque (Macaca mulatta) is the most widely used non-human primate for modeling the structure and function of the brain. 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. George is a senior staff reporter at Gizmodo. The brains were extracted and … Lifespan extensions reflect one of humanity’s most remarkable and underappreciated cultural accomplishments as the growing group of older individuals is one of few natural resources not diminishing. On average, southern pig-tailed macaques in Malaysia eat about 70 large rats each per Macaque brain. (B) Coronal Nissl-stained sections of hippocampus-containing tissue in the 3 species. Preserved specimen of the brain of a long-tailed macaque (Macaca fascicularis). An absolute must for all neuroscientists navigating the rhesus monkey brain."--Dr. We estimate that the relative rate of neurogenesis is approximately 10 times less than that reported in the adult rodent dentate gyrus. An important clue to a critical brain change that occurs in aging came from a study that used functional magnetic resonance imaging (fMRI) to demonstrate that the CA3/dentate gyrus region of the hippocampus is more active in older individuals than in younger adults as they attempt to discriminate increasingly overlapping visual stimuli (15). 2018-06: Visualize your own data inside a brain atlas with SBA Composer. 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. These anatomical differences between species are thought to reflect the drastically different acoustic sensitivities of primates and rodents. (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). 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). Evidence from an animal model of normal aging, Hilar interneuron vulnerability distinguishes aged rats with memory impairment, Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment, Memory impairment in aged primates is associated with region-specific network dysfunction, Neurobiological bases of age-related cognitive decline in the rhesus monkey, The effects of aging on area 46 of the frontal cortex of the rhesus monkey, The effects of age on the cells in layer 1 of primate cerebral cortex, Morphological analyses of the brains of behaviorally characterized aged nonhuman primates, Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys, Preservation of hippocampal neuron numbers in aged rhesus monkeys, Age-related changes in prefrontal cortex of Macaca mulatta: Synaptic density, Synapses are lost during aging in the primate prefrontal cortex, Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment, Effects of age on axon terminals forming axosomatic and axodendritic inhibitory synapses in prefrontal cortex, Topographical organization of the entorhinal projection to the dentate gyrus of the monkey, Preservation into old age of synaptic number and size in the supragranular layer of the dentate gyrus in rhesus monkeys, Synaptic correlates of memory and menopause in the hippocampal dentate gyrus in rhesus monkeys, Increased action potential firing rates of layer 2/3 pyramidal cells in the prefrontal cortex are significantly related to cognitive performance in aged monkeys, Neuronal basis of age-related working memory decline, Aging alters dendritic morphology, input resistance, and inhibitory signaling in dentate granule cells of the rhesus monkey, Protection of auditory receptors and neurons: Evidence for interactive damage, The Aging Auditory System, Springer Handbook of Auditory Research, Further observations on the pathology of presbycusis, Age-related changes in the response properties of cartwheel cells in rat dorsal cochlear nucleus, Age-related changes in the inhibitory response properties of dorsal cochlear nucleus output neurons: Role of inhibitory inputs, Inhibitory neurotransmission, plasticity and aging in the mammalian central auditory system, Alterations of GABAA receptor subunit mRNA levels in the aging Fischer 344 rat inferior colliculus, GABAA receptor binding in the aging rat inferior colliculus, Responses of young and aged rat inferior colliculus neurons to sinusoidally amplitude modulated stimuli, Reduced GABA(A) receptor-mediated tonic inhibition in aged rat auditory thalamus, Stimulus-specific adaptation in auditory thalamus of young and aged awake rats, Diminished cortical inhibition in an aging mouse model of chronic tinnitus, Hierarchical and serial processing in the spatial auditory cortical pathway is degraded by natural aging, Age-related neurochemical changes in the rhesus macaque inferior colliculus, Age-related neurochemical changes in the rhesus macaque superior olivary complex, Auditory peripheral influences on calcium binding protein immunoreactivity in the cochlear nucleus during aging in the C57BL/6J mouse, Age-related increases in calcium-binding protein immunoreactivity in the cochlear nucleus of hearing impaired C57BL/6J mice, Presbyacusis and calcium-binding protein immunoreactivity in the cochlear nucleus of BALB/c mice, Age-related changes in calbindin and calretinin immunoreactivity in the central auditory system of the rat, Changes in parvalbumin immunoreactivity with aging in the central auditory system of the rat, Age-related neurochemical changes in the rhesus macaque cochlear nucleus, Parvalbumin increases in the medial and lateral geniculate nuclei of aged rhesus macaques, Calcium-binding proteins in the nervous system, Viewpoint: The core and matrix of thalamic organization, Calbindin D-28k and parvalbumin in the rat nervous system, Introduction to the superior olivary complex, The lateral superior olive: A functional role in sound source localization, Neural mechanisms of encoding binaural localization cues in the auditory brainstem, Integrative Functions in the Mammalian Auditory Pathway, Springer Handbook of Auditory Research, Interaural time sensitivity in medial superior olive of cat, Microelectrode study of superior olivary nuclei, Topographic organization of the olivocochlear projections from the lateral and medial zones of the superior olivary complex. 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