Koji Toda

Neural mechanisms of social decision-making in the primate amygdala

Significance Making social decisions requires evaluation of benefits and costs to self and others. Long associated with emotion and vigilance, neurons in primate amygdala also signal reward and punishment as well as information about the faces and eyes of others. Here we show that neurons in the basolateral amygdala signal the value of rewards for self and others when monkeys make social decisions. These value-mirroring neurons reflected monkeys’ tendency to make prosocial decisions on a momentary as well as long-term basis. We also found that delivering the social peptide oxytocin into basolateral amygdala enhances both prosocial tendencies and attention to the recipients of prosocial decisions. Our findings endorse the amygdala as a critical neural nexus regulating social decisions. Social decisions require evaluation of costs and benefits to oneself and others. Long associated with emotion and vigilance, the amygdala has recently been implicated in both decision-making and social behavior. The amygdala signals reward and punishment, as well as facial expressions and the gaze of others. Amygdala damage impairs social interactions, and the social neuropeptide oxytocin (OT) influences human social decisions, in part, by altering amygdala function. Here we show in monkeys playing a modified dictator game, in which one individual can donate or withhold rewards from another, that basolateral amygdala (BLA) neurons signaled social preferences both across trials and across days. BLA neurons mirrored the value of rewards delivered to self and others when monkeys were free to choose but not when the computer made choices for them. We also found that focal infusion of OT unilaterally into BLA weakly but significantly increased both the frequency of prosocial decisions and attention to recipients for context-specific prosocial decisions, endorsing the hypothesis that OT regulates social behavior, in part, via amygdala neuromodulation. Our findings demonstrate both neurophysiological and neuroendocrinological connections between primate amygdala and social decisions.

Neurons in Monkey Dorsal Raphe Nucleus Code Beginning and Progress of Step-by-Step Schedule, Reward Expectation, and Amount of Reward Outcome in the Reward Schedule Task

The dorsal raphe nucleus is the major source of serotonin in the brain. It is connected to brain regions related to reward processing, and the neurons show activity related to predicted reward outcome. Clinical observations also suggest that it is important in maintaining alertness and its apparent role in addiction seems to be related to reward processing. Here, we examined whether the neurons in dorsal raphe carry signals about reward outcome and task progress during multitrial schedules. We recorded from 98 single neurons in dorsal raphe of two monkeys. The monkeys perform one, two, or three visual discrimination trials (schedule), obtaining one, two, or three drops of liquid. In the valid cue condition, the length and brightness of a visual cue indicated schedule progress and reward amount, respectively. In the random cue condition, the visual cue was randomly presented with respect to schedule length and reward amount. We found information encoded about (1) schedule onset, (2) reward expectation, (3) reward outcome, and (4) reward amount in the mean firing rates. Information theoretic analysis showed that the temporal variation of the neuronal responses contained additional information related to the progress of the schedule toward the reward rather than only discriminating schedule onset or reward/no reward. When considered in light of all that is known about the raphe in anatomy, physiology, and behavior, the rich encoding about both task progress and predicted reward outcome makes the raphe a strong candidate for providing signals throughout the brain to coordinate persistent goal-seeking behavior.

Animal cognition: Monkeys pass the mirror test

A new study finds that rhesus monkeys display self-recognition behaviors toward a mirror after multimodal sensory-motor training. This finding closes a prior gap in the evolutionary continuity of animal cognition and opens new frontiers for exploring the neurobiological basis of self-awareness.

Differential Encoding of Factors Influencing Predicted Reward Value in Monkey Rostral Anterior Cingulate Cortex

Background The value of a predicted reward can be estimated based on the conjunction of both the intrinsic reward value and the length of time to obtain it. The question we addressed is how the two aspects, reward size and proximity to reward, influence the responses of neurons in rostral anterior cingulate cortex (rACC), a brain region thought to play an important role in reward processing. Methods and Findings We recorded from single neurons while two monkeys performed a multi-trial reward schedule task. The monkeys performed 1–4 sequential color discrimination trials to obtain a reward of 1–3 liquid drops. There were two task conditions, a valid cue condition, where the number of trials and reward amount were associated with visual cues, and a random cue condition, where the cue was picked from the cue set at random. In the valid cue condition, the neuronal firing is strongly modulated by the predicted reward proximity during the trials. Information about the predicted reward amount is almost absent at those times. In substantial subpopulations, the neuronal responses decreased or increased gradually through schedule progress to the predicted outcome. These two gradually modulating signals could be used to calculate the effect of time on the perception of reward value. In the random cue condition, little information about the reward proximity or reward amount is encoded during the course of the trial before reward delivery, but when the reward is actually delivered the responses reflect both the reward proximity and reward amount. Conclusions Our results suggest that the rACC neurons encode information about reward proximity and amount in a manner that is dependent on utility of reward information. The manner in which the information is represented could be used in the moment-to-moment calculation of the effect of time and amount on predicted outcome value.

The influence of passband limitation on the waveform of extracellular action potential

The duration of the extracellular action potential (EAP) in single neuronal recording has often been used as a clue to infer biochemical, physiological or functional substrate of the recorded neurons, e.g. neurochemical type. However, when recording a neuronal activity, the high-pass filter is routinely used to achieve higher signal-to-noise ratio. Signal processing theory predicts that passband limitation stretches the waveform of discrete brief impulse. To examine whether the duration of filtered EAP could be the reliable measure, we investigated the influence of high-pass filter both by simulation and unfiltered unit recording data from monkey dorsal raphe. Consistent with the findings in recent theoretical study, the unfiltered EAPs displayed the sharp wave without following bumps. The duration of unfiltered EAP was not correlated with that of filtered EAP. Thus the duration of original EAP cannot be estimated from filtered EAP. It is needed to reexamine the EAP duration measured for classifying the neurons whose activities were recorded under the passband limitation in the related studies.

A craniofacial-specific monosynaptic circuit enables heightened affective pain

Humans often rank craniofacial pain as more severe than body pain. Evidence suggests that a stimulus of the same intensity induces stronger pain in the face than in the body. However, the underlying neural circuitry for the differential processing of facial versus bodily pain remains unknown. Interestingly, the lateral parabrachial nucleus (PBL), a critical node in the affective pain circuit, is activated more strongly by noxious stimulation of the face than of the hindpaw. Using a novel activity-dependent technology called CANE developed in our laboratory, we identified and selectively labeled noxious-stimulus-activated PBL neurons and performed comprehensive anatomical input–output mapping. Surprisingly, we uncovered a hitherto uncharacterized monosynaptic connection between cranial sensory neurons and the PBL-nociceptive neurons. Optogenetic activation of this monosynaptic craniofacial-to-PBL projection induced robust escape and avoidance behaviors and stress calls, whereas optogenetic silencing specifically reduced facial nociception. The monosynaptic circuit revealed here provides a neural substrate for heightened craniofacial affective pain.The authors show that unlike body sensory neurons, craniofacial nociceptive neurons directly synapse with noxious-stimulus-activated lateral parabrachial neurons (PBL), which in turn project to multiple limbic centers processing emotions and affects. This monosynaptic pathway is both sufficient and necessary for craniofacial-pain-activated aversive behaviors.

Publisher Correction: A craniofacial–specific monosynaptic circuit enables heightened affective pain

In the version of this article initially published, ORCID links were missing for authors Erica Rodriguez, Koji Toda and Fan Wang. The error has been corrected in the HTML and PDF versions of the article.

Measuring the actual timing of liquid-reward delivery using a thermistor.

BACKGROUND Determining the exact timing of reward delivery is critical in neurophysiological experiments. Despite the importance of this parameter, techniques for precisely measuring the exact delivery time of a liquid reward have been underdeveloped. Although there is always some latency between the computer command and reward delivery, the former has been used routinely to mark reward onset time. NEW METHOD To address this issue, we developed two methods of estimating the time of liquid reward delivery. First, electrical conduction between two contacts at the outlet of a pipe was detected. This technique was impractical during normal experiments but was a direct and reliable method of measuring the precise timing of water outflow. Second, a self-heating thermistor inside the fluid delivery pipe was used. The thermistor detected a decrease in temperature upon commencement of water flow. RESULTS The electrical contact began 50-80ms after the computer command. The thermistor-based delivery timing estimation was ∼40ms later than that measured by the electrical contact. The time lag was constant with minimal variance between trials within the same experimental setup. COMPARISON WITH EXISTING METHOD As far as the time difference between the two methods is measured, the timing of water outflow can be estimated using the thermistor-based device. This is the first method of estimating the onset time of water flow during experiments. CONCLUSIONS Our new system could be used to quantify setup-dependent changes in the timing of reward delivery, improving the sophistication of reward assessments in neurophysiological experiments.

Single neurons in monkey dorsal raphe nucleus responded in multi-trial reward schedule task with different reward amount

We studied the axonal morphology of single presubicular neurons in the rat, with a viral vector expressing membrane-targeted GFP. A single pyramidal neuron in layer III of the presubiculum (PreS) had six axon collaterals, three of which reached layer III of the medial entorhinal area (MEA), one passed through the dorsal hippocampal commissure, and two recurrently reached layers V and VI of PreS. Another single pyramidal neuron in layer V had four axon collaterals that projected to layers V and VI of the retrosplenial cortex and one recurrent collateral that reached layer VI of PreS. A single non-pyramidal layer VI neuron had four axon collaterals; one innervated layers V and VI of MEA, one entered the white matter, and two recurrently reached layers V and VI of PreS. Our data demonstrate for the first time some characteristic patterns of axonal collateralization of single corticocortical projection neurons in each layer of the rat presubiculum.

Effects of reward proximity and amount on neural activity in the rostral anterior cingulate cortex

We studied the axonal morphology of single presubicular neurons in the rat, with a viral vector expressing membrane-targeted GFP. A single pyramidal neuron in layer III of the presubiculum (PreS) had six axon collaterals, three of which reached layer III of the medial entorhinal area (MEA), one passed through the dorsal hippocampal commissure, and two recurrently reached layers V and VI of PreS. Another single pyramidal neuron in layer V had four axon collaterals that projected to layers V and VI of the retrosplenial cortex and one recurrent collateral that reached layer VI of PreS. A single non-pyramidal layer VI neuron had four axon collaterals; one innervated layers V and VI of MEA, one entered the white matter, and two recurrently reached layers V and VI of PreS. Our data demonstrate for the first time some characteristic patterns of axonal collateralization of single corticocortical projection neurons in each layer of the rat presubiculum.