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Biomedical subjects

Michael L Platt

Publications and source records attributed to Michael L Platt.

8 recordsLinked to original sources

Age and early life adversity shape heterogeneity of the epigenome across tissues in macaques.

Age and early life adversity (ELA) are key determinants of health, but whether they affect similar physiological mechanisms across tissues is unknown. We generated DNA methylation (DNAm) profiles across 14 tissues in 237 semi-free-ranging rhesus macaques with naturally occurring ELA. Age-associated DNAm was predominantly tissue dependent, yet tissue-specific epigenetic clocks showed that epigenetic aging was relatively consistent within individuals. ELA effects were adversity dependent, but each ELA exerted coordinated effects across tissues. Although ELA targeted many of the same loci as age, the directions of effects differed, which indicates that ELA does not uniformly increase epigenetic age. Instead, ELA leaves a coordinated, cross-tissue epigenetic signature that is distinct from-yet intertwined with-age-related differences, which advances our understanding of how early environments sculpt the molecular foundations of aging and disease.

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Visual and saccade-related activity in macaque posterior cingulate cortex.

Previous neurophysiological studies have reported that neurons in posterior cingulate cortex (PCC) respond after eye movements, and that these responses may vary with ambient illumination. In monkeys, PCC neurons also respond after the illumination of large visual patterns but not after the illumination of small visual targets on either reflexive saccade tasks or peripheral attention tasks. These observations suggest that neuronal activity in PCC is modulated by behavioral context, which varies with the timing and spatial distribution of visual and oculomotor events. To test this hypothesis, we measured the spatial and temporal response properties of single PCC neurons in monkeys performing saccades in which target location and movement timing varied unpredictably. Specifically, an unsignaled delay between target onset and movement onset permitted us to temporally dissociate changes in PCC activity associated with either event. Response fields constructed from these data demonstrated that many PCC neurons were activated after the illumination of small contralateral visual targets, as well as after the onset of contraversive saccades guided by those targets. In addition, the PCC population maintained selectivity for small contralateral targets during delays of up to 600 ms. Overall, PCC activation was highly variable trial to trial and selective for a broad range of directions and amplitudes. Planar functions described response fields nearly as well as broadly tuned 2-dimensional Gaussian functions. Additionally, the overall responsiveness of PCC neurons decreased during delays when both a fixation stimulus and a saccade target were visible, suggesting a modulation by divided attention. Finally, the strength of the neuronal response after target onset was correlated with saccade accuracy on delayed-saccade trials. Thus PCC neurons may signal salient visual and oculomotor events, consistent with a role in visual orienting and attention.

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Saccade reward signals in posterior cingulate cortex.

Movement selection depends on the outcome of prior behavior. Posterior cingulate cortex (CGp) is strongly connected with both limbic and oculomotor circuitry, and CGp neurons respond following saccades, suggesting a role in signaling the motivational outcome of gaze shifts. To test this hypothesis, single CGp neurons were studied in monkeys while they shifted gaze to visual targets for liquid rewards that varied in size or were delivered probabilistically. CGp neurons responded following saccades as well as following reward delivery, and these responses were correlated with reward size. CGp neurons also responded following the omission of predicted rewards. The timing of CGp activation and its modulation by reward could provide signals useful for updating representations of expected saccade value.

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Reflexive social attention in monkeys and humans.

For humans, social cues often guide the focus of attention. Although many nonhuman primates, like humans, live in large, complex social groups, the extent to which human and nonhuman primates share fundamental mechanisms of social attention remains unexplored. Here, we show that, when viewing a rhesus macaque looking in a particular direction, both rhesus macaques and humans reflexively and covertly orient their attention in the same direction. Specifically, when performing a peripheral visual target detection task, viewing a monkey with either its eyes alone or with both its head and eyes averted to one side facilitated the detection of peripheral targets when they randomly appeared on the same side. Moreover, viewing images of a monkey with averted gaze evoked small but systematic shifts in eye position in the direction of gaze in the image. The similar magnitude and temporal dynamics of response facilitation and eye deviation in monkeys and humans suggest shared neural circuitry mediating social attention.

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Caudate clues to rewarding cues.

Behavioral studies indicate that prior experience can influence discrimination of subsequent stimuli. The mechanisms responsible for highlighting a particular aspect of the stimulus, such as motion or color, as most relevant and thus deserving further scrutiny, however, remain poorly understood. In the current issue of Neuron, demonstrate that neurons in the caudate nucleus of the basal ganglia signal which dimension of a visual cue, either color or location, is associated with reward in an eye movement task. These findings raise the possibility that this structure participates in the reward-based control of visual attention.

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Neural correlates of decisions.

Once considered the province of philosophy and the behavioral sciences, the process of making decisions has received increasing scrutiny from neurobiologists. Recent research suggests that sensory judgements unfold through the gradual accumulation of neuronal signals in sensory-motor pathways, favoring one alternative over others. Stored representations of the outcome of prior actions activate neurons in many of these same areas during decision-making. The challenge for neurobiologists lies in deciphering how signals from these disparate areas are integrated to form a single behavioral choice and the mechanisms responsible for selecting the appropriate information upon which decisions should be informed in particular contexts.

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