Munetaka Shidara

Role of Purkinje Cells in the Ventral Paraflocculus in Short-latency Ocular Following Responses

We describe the simple-spike activity of Purkin je cells (P cells) in the ventral paraflocculus (VPFL) of behaving monkeys in association with movements of the visual scene that evoke short-latency ocular following re sponses. One group of P cells discharged maximally for downward motion, and the other for motion toward the side of the recording. The onset of the simple-spike re sponse was measured in relation to the onset of ocular following in 24 P cells. The majority of P cells (79%) led by 1–9 ms. At the site of each recording, electrical stimuli (single negative pulses, 1.5–45 μA; 0.2 ms in width) were applied and 60% (18/30) of the sites elicited eye movements in the preferred direction of the P cells. The latency of the single-pulse-evoked response in the ipsilateral eye ranged from 8.6 to 10.9 ms. These data suggest that the P cells in the VPFL play a role in ocular following; some discharge early enough to generate the very earliest eye movements.

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.

Changes in sodium channels during neural differentiation in the isolated blastomere of the ascidian embryo.

1. The current density and the kinetics of voltage‐sensitive sodium channels during neural differentiation were examined in the isolated, cleavage‐arrested blastomere of ascidian embryos which contains presumptive neural regions. The macroscopic sodium current were measured with the two‐microelectrode voltage‐clamp technique and the single sodium channel currents were recorded with the patch‐clamp technique under the cell‐attached configuration. 2. The entire time course of sodium channel development could be divided into three phases from the current density and channel gating properties. 3. In the first phase, from fertilization to about 40 h, the density of the sodium channel current was from 8 to 50 microA cm‐2. The channel gating properties were similar to those of the sodium channel in the egg cell except for a negative shift in the voltage dependence of the peak inward current, the steady‐state inactivation, and the decay time constant. The sodium channels in this phase were classified as ‘type‐I’ channels. 4. In the second phase (40‐60 h after fertilization), the density of the sodium channel current increased from 20 to 800 microA cm‐2. The curves of the I‐V relationship and of the steady‐state inactivation shifted in the positive direction by 5‐10 mV. 5. At 45‐55 h, when the rate of increase in the sodium current was greatest, as much as 40 microA cm‐2 h‐1, the decay time course of the sodium current became slowest. The time for the current to decline from the peak to the one‐tenth of the peak (t 1/10) increased to about five times that in the first phase. After 55 h t 1/10 gradually decreased. 6. In this phase, steady‐state inactivation curves showed two inflexion points at different levels of membrane potential and were fitted with a sum of two Boltzmann distribution curves with distinct parameters. The relative contribution of the component with its voltage dependence shifted in the positive direction tended to decrease with development. 7. On examining single‐channel recordings, two types of sodium channel were identified in this phase. One type (type‐II) showed frequent repetitions of open‐to‐shut states throughout a voltage step. The ensemble current of the type‐II channel showed a slow decay, suggesting that this type of channel may underlie the markedly slow decay of the macroscopic current in this phase. The second type (type‐III) had more late openings than the type‐I channel but fewer than the type‐II channel.(ABSTRACT TRUNCATED AT 400 WORDS)

A comparison of reward-contingent neuronal activity in monkey orbitofrontal cortex and ventral striatum: guiding actions toward rewards.

Abstract:  We have investigated how neuronal activity in the orbitofrontal‐ventral striatal circuit is related to reward‐directed behavior by comparing activity in these two regions during a visually guided reward schedule task. When a set of visual cues provides information about reward contingency, that is, about whether or not a trial will be rewarded, significant subpopulations of neurons in both orbitofrontal cortex and ventral striatum encode this information. Orbitofrontal and ventral striatal neurons also differentiate between rewarding and non‐rewarding trial outcomes, whether or not those outcomes were predicted. The size of the neuronal subpopulation encoding reward contingency is twice as large in orbitofrontal cortex (50% of neurons) as in ventral striatum (26%). Reward‐contingency‐dependent activity also appears earlier during a trial in orbitofrontal cortex than in ventral striatum. The peak reward‐contingency representation in orbitofrontal cortex (31% of neurons), occurs during the wait period, a period of high anticipation prior to any action. The peak ventral striatal representation of reward contingency (18%) occurs during the go period, a time of action. We speculate that signals from orbitofrontal cortex bias ventral striatal activity, and that a flow of reward‐contingency information from orbitofrontal cortex to ventral striatum serves to guide actions toward rewards.

Developmental changes in delayed rectifier K+ currents in the muscular- and neural-type blastomere of ascidian embryos

1. Developmental changes in the amplitude, kinetic properties, tetraethyl‐ammonium (TEA) sensitivity, and ion selectivity of the delayed rectifier K+ currents were investigated in differentiating muscular‐type (M) and neural‐type (N) blastomeres isolated from the early cleavage‐arrested ascidian embryos, using conventional two‐microelectrode voltage clamp techniques. 2. No voltage‐sensitive outward K+ currents were found in either type of blastomere during the first 35 h of development at 9 degrees C. Thereafter the delayed rectifier K+ current became apparent. The peak amplitude of the K+ current in the M‐blastomere increased abruptly from 50 to 60 h and tended to plateau after 60 h, while in the N‐blastomere it continued to increase after initial emergence at around 35 h. 3. The threshold potential level of the K+ current in the M‐blastomere was initially about ‐10 mV in a standard external solution (1 mM‐K+ solution), but shifted towards the hyperpolarized direction until it reached a steady level at 45 h after fertilization. At the fully differentiated stages, the threshold was around ‐32 mV and ‐26 mV in the M‐ and N‐blastomeres, respectively. 4. Throughout development, the reversal potential of the tail current changed with the external K+ concentration in both M‐ and N‐blastomeres as expected for a K(+)‐electrode. There was no significant difference in the selectivity ratios for the K+ channel between the two types of blastomeres. The relative selectivities were K+ (1.000): Rb+ (0.774): NH4+ (0.122): Na+ (0.074) and K+ (1.000): Rb+ (0.724): NH4+ (0.155): Na+ (0.074) in the M‐ and N‐blastomeres, respectively. 5. Modified Scatchard plots of TEA‐sensitivity data indicated a one‐to‐one reaction between TEA and the K+ channel. These plots revealed the presence of TEA‐resistant K+ channels in addition to TEA‐sensitive K+ channels in the M‐blastomere, but revealed only TEA‐sensitive K+ channels in the N‐blastomere. The dissociation constant (Ki) values of these three types of K+ channel did not change during development. In the M‐blastomere, the Ki of the TEA‐sensitive K+ channel was 1.29 +/‐ 0.05 mM (mean +/‐ S.E.M., n = 31) and that of the TEA‐resistant K+ channel was 1.4 +/‐ 0.1 M (mean +/‐ S.E.M., n = 31) at a test potential of 45 mV. The Ki value of the neural‐type K+ current was 1.38 +/‐ 0.03 mM (mean +/‐ S.E.M., n = 20) at 45 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Encoding of reward expectation by monkey anterior insular neurons

The insula, a cortical brain region that is known to encode information about autonomic, visceral, and olfactory functions, has recently been shown to encode information during reward-seeking tasks in both single neuronal recording and functional magnetic resonance imaging studies. To examine the reward-related activation, we recorded from 170 single neurons in anterior insula of 2 monkeys during a multitrial reward schedule task, where the monkeys had to complete a schedule of 1, 2, 3, or 4 trials to earn a reward. In one block of trials a visual cue indicated whether a reward would or would not be delivered in the current trial after the monkey successfully detected that a red spot turned green, and in other blocks the visual cue was random with respect to reward delivery. Over one-quarter of 131 responsive neurons were activated when the current trial would (certain or uncertain) be rewarded if performed correctly. These same neurons failed to respond in trials that were certain, as indicated by the cue, to be unrewarded. Another group of neurons responded when the reward was delivered, similar to results reported previously. The dynamics of population activity in anterior insula also showed strong signals related to knowing when a reward is coming. The most parsimonious explanation is that this activity codes for a type of expected outcome, where the expectation encompasses both certain and uncertain rewards.

Neuronal firing in anterior cingulate neurons changes modes across trials in single states of multitrial reward schedules

The recorded responses of single neurons often vary considerably in the numbers of spikes emitted across repeats of a single experimental condition. Because of this irregularity and for theoretical convenience the responses are often approximated using a Poisson process. However, it has been frequently pointed out that many details of the responses, including the distribution of spike counts across similar trials, are not consistent with a Poisson process, even an inhomogeneous one. Wiener and Richmond (2003, J Neurosci 23:2394–2406) showed that the spike count distributions could usually be fitted nicely by mixtures of a few (1–3) Poisson distributions, a step they regarded as a computational convenience. Now, we find that a substantial proportion (47%) of the neuronal responses from anterior cingulate cortex, which we conceptualize as part of a system related to the balance between work and reward, have responses with multimodal firing rate distributions. When these distributions are modeled as mixtures of Poisson distributions, the proportions of the different Poisson distributions are related to behavioral state, and might be related to cognitive factors. This suggests that the neurons undergo behaviorally-related mode changes.

Differential encoding of information about progress through multi-trial reward schedules by three groups of ventral striatal neurons.

In the course of daily activity we continually judge whether the goal sought is worth the work that must be done to obtain it. The ventral striatum is thought to play a central role in making such judgments. When reward schedules are used to investigate these judgments ventral striatum neurons show responses near the time of the cue, the bar-release, and/or the reward delivery. We evaluated the type of coding that occurs at these three time points by using codes or factorizations with: (1) two states for reward versus non-reward, (2) four states for the progress in the reward schedule, and (3) six states for all of the states of the schedule, quantified using information theory and ANOVA. For the bar-release- and reward-related responses the percent variance explained was as high for the two states code as with the six states code. The information for the four state code rose slightly but significantly for the bar-release-related neurons. For the cue-related neurons the code with six states carried more information than the simpler codes. Thus, responses at different times appear to play different roles. Responses occurring early in trials differentiate all states, i.e., the path to a reward, whereas those late in trials code knowledge of impending reward.

Stimulus-Related Activity during Conditional Associations in Monkey Perirhinal Cortex Neurons Depends on Upcoming Reward Outcome

Acquiring the significance of events based on reward-related information is critical for animals to survive and to conduct social activities. The importance of the perirhinal cortex for reward-related information processing has been suggested. To examine whether or not neurons in this cortex represent reward information flexibly when a visual stimulus indicates either a rewarded or unrewarded outcome, neuronal activity in the macaque perirhinal cortex was examined using a conditional-association cued-reward task. The task design allowed us to study how the neuronal responses depended on the animals prediction of whether it would or would not be rewarded. Two visual stimuli, a color stimulus as Cue1 followed by a pattern stimulus as Cue2, were sequentially presented. Each pattern stimulus was conditionally associated with both rewarded and unrewarded outcomes depending on the preceding color stimulus. We found an activity depending upon the two reward conditions during Cue2, i.e., pattern stimulus presentation. The response appeared after the response dependent upon the image identity of Cue2. The response delineating a specific cue sequence also appeared between the responses dependent upon the identity of Cue2 and reward conditions. Thus, when Cue1 sets the context for whether or not Cue2 indicates a reward, this region represents the meaning of Cue2, i.e., the reward conditions, independent of the identity of Cue2. These results suggest that neurons in the perirhinal cortex do more than associate a single stimulus with a reward to achieve flexible representations of reward information.

Effect of visual noise on pattern recognition

We recognize objects even when they are partially degraded by visual noise. Using monkeys performing a sequential delayed match-to-sample task, we studied the relation between the amount of visual noise (5, 10, 15, 20 or 25%) degrading the eight black and white stimuli used here, and the accuracy and speed with which matching stimuli were identified. The correct response rate decreased slightly as the amount of visual noise increased for both monkeys. Even at the 25% noise level, the correct response rate was more than 80%, indicating that the monkeys can recognize the pattern they are trying to match when the pattern is masked with visual noise. In contrast, the reaction time to the match stimulus increased substantially as the amount of visual noise increased. Thus, the monkeys appear to be trading time to maintain accuracy, suggesting that the monkeys are accumulating information and/or testing hypotheses about whether the test stimulus is likely to be a match for the sample being held in short-term memory.