People attend not only to their own experiences, but also to the experiences of those around them. Such social awareness profoundly influences human behavior by enabling observational learning, as ...well as by motivating cooperation, charity, empathy, and spite. Oxytocin (OT), a neurosecretory hormone synthesized by hypothalamic neurons in the mammalian brain, can enhance affiliation or boost exclusion in different species in distinct contexts, belying any simple mechanistic neural model. Here we show that inhaled OT penetrates the CNS and subsequently enhances the sensitivity of rhesus macaques to rewards occurring to others as well as themselves. Roughly 2 h after inhaling OT, monkeys increased the frequency of prosocial choices associated with reward to another monkey when the alternative was to reward no one. OT also increased attention to the recipient monkey as well as the time it took to render such a decision. In contrast, within the first 2 h following inhalation, OT increased selfish choices associated with delivery of reward to self over a reward to the other monkey, without affecting attention or decision latency. Despite the differences in species typical social behavior, exogenous, inhaled OT causally promotes social donation behavior in rhesus monkeys, as it does in more egalitarian and monogamous ones, like prairie voles and humans, when there is no perceived cost to self. These findings potentially implicate shared neural mechanisms.
The enormous influence of hierarchical rank on social interactions 1 suggests that neural mechanisms exist to process status-related information 2 and ascribe value to it. The ventral striatum is ...prominently implicated in processing value and salience, independent of hedonic properties 3, 4, and a functional magnetic resonance imaging (fMRI) study of social status perception in humans demonstrated that viewing higher-ranked compared to lower-ranked individuals evokes a ventral striatal response 5, indicative of a greater assignment of value/salience to higher status. Consistent with this interpretation, nonhuman primates value information associated with higher-ranked conspecifics more than lower-ranked, as illustrated using a choice paradigm in which monkeys preferentially take the opportunity to view high-status monkeys 6. Interestingly, this status-related value assignment in nonhuman primates is influenced by one's own hierarchical rank: high-status monkeys preferentially attend to conspecifics of high status, whereas low-status monkeys will also attend to other low-status monkeys 7. Complementary to these findings, using fMRI and a social status judgment task in humans, we suggest a neurobiological mechanism by which one's own relative hierarchical rank influences the value attributed to particular social status information by demonstrating that one's subjective socioeconomic status differentially influences ventral striatal activity during processing of status-related information.
► One's socioeconomic status influences ventral striatal responses to social rank cues ► In high-status subjects, exposure to higher-rank information engages ventral striatum ► In low-status subjects, exposure to lower-rank information engages ventral striatum ► Results suggest biological mechanism by which one's rank influences status cue value
The compatibility of
W
-boson mass measurements performed by the ATLAS, LHCb, CDF, and D0 experiments is studied using a coherent framework with theory uncertainty correlations. The measurements are ...combined using a number of recent sets of parton distribution functions (PDF), and are further combined with the average value of measurements from the Large Electron–Positron collider. The considered PDF sets generally have a low compatibility with a suite of global rapidity-sensitive Drell–Yan measurements. The most compatible set is CT18 due to its larger uncertainties. A combination of all
m
W
measurements yields a value of
m
W
=
80
,
394.6
±
11.5
MeV with the CT18 set, but has a probability of compatibility of 0.5% and is therefore disfavoured. Combinations are performed removing each measurement individually, and a 91% probability of compatibility is obtained when the CDF measurement is removed. The corresponding value of the
W
boson mass is
80
,
369.2
±
13.3
MeV, which differs by
3.6
σ
from the CDF value determined using the same PDF set.
To understand the neural basis of behavior, it is necessary to record brain activity in freely moving animals. Advances in implantable multi-electrode array technology have enabled researchers to ...record the activity of neuronal ensembles from multiple brain regions. The full potential of this approach is currently limited by reliance on cable tethers, with bundles of wires connecting the implanted electrodes to the data acquisition system while impeding the natural behavior of the animal. To overcome these limitations, here we introduce a multi-channel wireless headstage system designed for small animals such as rats and mice. A variety of single unit and local field potential signals were recorded from the dorsal striatum and substantia nigra in mice and the ventral striatum and prefrontal cortex simultaneously in rats. This wireless system could be interfaced with commercially available data acquisition systems, and the signals obtained were comparable in quality to those acquired using cable tethers. On account of its small size, light weight, and rechargeable battery, this wireless headstage system is suitable for studying the neural basis of natural behavior, eliminating the need for wires, commutators, and other limitations associated with traditional tethered recording systems.
Luminopsins are fusion proteins of luciferase and opsin that allow interrogation of neuronal circuits at different temporal and spatial resolutions by choosing either extrinsic physical or intrinsic ...biological light for its activation. Building on previous development of fusions of wild-type Gaussia luciferase with channelrhodopsin, here we expanded the utility of luminopsins by fusing bright Gaussia luciferase variants with either channelrhodopsin to excite neurons (luminescent opsin, LMO) or a proton pump to inhibit neurons (inhibitory LMO, iLMO). These improved LMOs could reliably activate or silence neurons in vitro and in vivo. Expression of the improved LMO in hippocampal circuits not only enabled mapping of synaptic activation of CA1 neurons with fine spatiotemporal resolution but also could drive rhythmic circuit excitation over a large spatiotemporal scale. Furthermore, virus-mediated expression of either LMO or iLMO in the substantia nigra in vivo produced not only the expected bidirectional control of single unit activity but also opposing effects on circling behavior in response to systemic injection of a luciferase substrate. Thus, although preserving the ability to be activated by external light sources, LMOs expand the use of optogenetics by making the same opsins accessible to noninvasive, chemogenetic control, thereby allowing the same probe to manipulate neuronal activity over a range of spatial and temporal scales.
Here, we use a mouse model (DBA/2J) to readdress the location of insult(s) to retinal ganglion cells (RGCs) in glaucoma. We localize an early sign of axon damage to an astrocyte-rich region of the ...optic nerve just posterior to the retina, analogous to the lamina cribrosa. In this region, a network of astrocytes associates intimately with RGC axons. Using BAX-deficient DBA/2J mice, which retain all of their RGCs, we provide experimental evidence for an insult within or very close to the lamina in the optic nerve. We show that proximal axon segments attached to their cell bodies survive to the proximity of the lamina. In contrast, axon segments in the lamina and behind the eye degenerate. Finally, the Wlds allele, which is known to protect against insults to axons, strongly protects against DBA/2J glaucoma and preserves RGC activity as measured by pattern electroretinography. These experiments provide strong evidence for a local insult to axons in the optic nerve.
A major output nucleus of the basal ganglia is the substantia nigra pars reticulata, which sends GABAergic projections to brainstem and thalamic nuclei. The GABAergic (GABA) neurons are reciprocally ...connected with nearby dopaminergic neurons, which project mainly to the basal ganglia, a set of subcortical nuclei critical for goal-directed behaviors. Here we examined the impact of motivational states on the activity of GABA neurons in the substantia nigra pars reticulata and the neighboring dopaminergic (DA) neurons in the pars compacta. Both types of neurons show short-latency bursts to a cue predicting a food reward. As mice became sated by repeated consumption of food pellets, one class of neurons reduced cue-elicited firing, whereas another class of neurons progressively increased firing. Extinction or pre-feeding just before the test session dramatically reduced the phasic responses and their motivational modulation. These results suggest that signals related to the current motivational state bidirectionally modulate behavior and the magnitude of phasic response of both DA and GABA neurons in the substantia nigra.
The basal ganglia (BG) are implicated in many movement disorders, yet how they contribute to movement remains unclear. Using wireless in vivo recording, we measured BG output from the substantia ...nigra pars reticulata (SNr) in mice while monitoring their movements with video tracking. The firing rate of most nigral neurons reflected Cartesian coordinates (either x- or y-coordinates) of the animal's head position during movement. The firing rates of SNr neurons are either positively or negatively correlated with the coordinates. Using an egocentric reference frame, four types of neurons can be classified: each type increases firing during movement in a particular direction (left, right, up, down), and decreases firing during movement in the opposite direction. Given the high correlation between the firing rate and the x and y components of the position vector, the movement trajectory can be reconstructed from neural activity. Our results therefore demonstrate a quantitative and continuous relationship between BG output and behavior. Thus, a steady BG output signal from the SNr (i.e., constant firing rate) is associated with the lack of overt movement, when a stable posture is maintained by structures downstream of the BG. Any change in SNr firing rate is associated with a change in position (i.e., movement). We hypothesize that the SNr output quantitatively determines the direction, velocity, and amplitude of voluntary movements. By changing the reference signals to downstream position control systems, the BG can produce transitions in body configurations and initiate actions.
The contribution of basal ganglia outputs to consummatory behavior remains poorly understood. We recorded from the substantia nigra pars reticulata (SNR), the major basal ganglia output nucleus, ...during self-initiated drinking in mice. The firing rates of many lateral SNR neurons were time-locked to individual licks. These neurons send GABAergic projections to the deep layers of the orofacial region of the lateral tectum (superior colliculus, SC). Many tectal neurons were also time-locked to licking, but their activity was usually in antiphase with that of SNR neurons, suggesting inhibitory nigrotectal projections. We used optogenetics to selectively activate the GABAergic nigrotectal afferents in the deep layers of the SC. Photo-stimulation of the nigrotectal projections transiently inhibited the activity of the lick-related tectal neurons, disrupted their licking-related oscillatory pattern and suppressed self-initiated drinking. These results demonstrate that GABAergic nigrotectal projections have a crucial role in coordinating drinking behavior.
Researchers have yet to apply a formal operationalized theory of motivation to neurobiology that would more accurately and precisely define neural activity underlying motivation. We overcome this ...challenge with the novel application of the Expectancy Theory of Motivation to human fMRI to identify brain activity that explicitly reflects motivation. Expectancy Theory quantitatively describes how individual constructs determine motivation by defining motivation force as the product of three variables: expectancy – belief that effort will better performance; instrumentality – belief that successful performance leads to particular outcome, and valence – outcome desirability. Here, we manipulated information conveyed by reward-predicting cues such that relative cue-evoked activity patterns could be statistically mapped to individual Expectancy Theory variables. The variable associated with activity in any voxel is only reported if it replicated between two groups of healthy participants. We found signals in midbrain, ventral striatum, sensorimotor cortex, and visual cortex that specifically map to motivation itself, rather than other factors. This is important because, for the first time, it empirically clarifies approach motivation neural signals during reward anticipation. It also highlights the effectiveness of the application of Expectancy Theory to neurobiology to more precisely and accurately probe motivation neural correlates than has been achievable previously.
•Expectancy Theory provides a formal operational definition of motivation.•For the first time, we apply Expectancy Theory to fMRI to study motivation signals precisely.•With Expectancy Theory, motivation fMRI signals are isolated from reward and other processes.•Signals in ventral striatum, midbrain, sensorimotor, and visual cortex scale specifically with evoked motivation.•This highlights the effectiveness of applying Expectancy Theory to probe motivation neurobiology.
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