Electrical Stimulation of the Primate Lateral Habenula Suppresses Saccadic Eye Movement through a Learning Mechanism

The lateral habenula (LHb) is a brain structure which represents negative motivational value. Neurons in the LHb are excited by unpleasant events such as reward omission and aversive stimuli, and transmit these signals to midbrain dopamine neurons which are involved in learning and motivation. However, it remains unclear whether these phasic changes in LHb neuronal activity actually influence animal behavior. To answer this question, we artificially activated the LHb by electrical stimulation while monkeys were performing a visually guided saccade task. In one block of trials, saccades to one fixed direction (e.g., right direction) were followed by electrical stimulation of the LHb while saccades to the other direction (e.g., left direction) were not. The direction-stimulation contingency was reversed in the next block. We found that the post-saccadic stimulation of the LHb increased the latencies of saccades in subsequent trials. Notably, the increase of the latency occurred gradually as the saccade was repeatedly followed by the stimulation, suggesting that the effect of the post-saccadic stimulation was accumulated across trials. LHb stimulation starting before saccades, on the other hand, had no effect on saccade latency. Together with previous studies showing LHb activation by reward omission and aversive stimuli, the present stimulation experiment suggests that LHb activity contributes to learning to suppress actions which lead to unpleasant events

Causal Role of Neural Signals Transmitted From the Frontal Eye Field to the Superior Colliculus in Saccade Generation

The frontal eye field (FEF) and superior colliculus (SC) are major and well-studied components of the oculomotor system. The FEF sends strong projections to the SC directly, and neurons in these brain regions transmit a variety of signals related to saccadic eye movements. Electrical microstimulation and pharmacological manipulation targeting the FEF or SC affect saccadic eye movements. These data suggest the causal contribution of each region to saccade generation. To understand how the brain generates behavior, however, it is critical not only to identify the structures and functions of individual regions, but also to elucidate how they interact with each other. In this review article, we first survey previous works that aimed at investigating whether and how the FEF and SC interact to regulate saccadic eye movements using electrophysiological and pharmacological techniques. These works have reported what signals FEF neurons transmit to the SC and what roles such signals play in regulating oculomotor behavior. We then highlight a recent attempt of our own that has applied an optogenetic approach to stimulate the neural pathway from the FEF to the SC in nonhuman primates. This study has shown that optogenetic stimulation of the FEF-SC pathway is sufficiently effective not only to modulate SC neuron activity, but also to evoke saccadic eye movements. Although the oculomotor system is a complex neural network composed of numbers of cortical and subcortical regions, the optogenetic approach will provide a powerful strategy for elucidating the role of each neural pathway constituting this network

Dopamine in Motivational Control: Rewarding, Aversive, and Alerting

Midbrain dopamine neurons are well known for their strong responses to rewards and their critical role in positive motivation. It has become increasingly clear, however, that dopamine neurons also transmit signals related to salient but nonrewarding experiences such as aversive and alerting events. Here we review recent advances in understanding the reward and nonreward functions of dopamine. Based on this data, we propose that dopamine neurons come in multiple types that are connected with distinct brain networks and have distinct roles in motivational control. Some dopamine neurons encode motivational value, supporting brain networks for seeking, evaluation, and value learning. Others encode motivational salience, supporting brain networks for orienting, cognition, and general motivation. Both types of dopamine neurons are augmented by an alerting signal involved in rapid detection of potentially important sensory cues. We hypothesize that these dopaminergic pathways for value, salience, and alerting cooperate to support adaptive behavior

The Formation of Population III Binaries

We explore the possibility for the formation of Population III binaries. The collapse of a rotating cylinder is simulated with a three-dimensional, high-resolution nested grid, assuming the thermal history of primordial gas. The simulations are done with dimensionless units, and the results are applicable to low-mass as well as massive systems by scaling with the initial density. We find that if the initial angular momentum is as small as $\beta \approx 0.1$, where $\beta$ is the ratio of centrifugal force to pressure force, then the runaway collapse of the cloud stops to form a rotationally-supported disk. After the accretion of the envelope, the disk undergoes a ring instability, eventually fragmenting into a binary. If the initial angular momentum is relatively large, a bar-type instability arises, resulting in the collapse into a single star through rapid angular momentum transfer. The present results show that a significant fraction of Pop III stars are expected to form in binary systems, even if they are quite massive or less massive. The cosmological implications of Population III binaries are briefly discussed.Comment: Astrophysical Journal Letter, in press. 10 pages, 2 color figures, (full paper with high-resolution figures available at http://yso.mtk.nao.ac.jp/~saigo/papers/saigo2004a/saigo2004.pdf

Coreference based event-argument relation extraction on biomedical text

This paper presents a new approach to exploit coreference information for extracting event-argument (E-A) relations from biomedical documents. This approach has two advantages: (1) it can extract a large number of valuable E-A relations based on the concept of salience in discourse; (2) it enables us to identify E-A relations over sentence boundaries (cross-links) using transitivity of coreference relations. We propose two coreference-based models: a pipeline based on Support Vector Machine (SVM) classifiers, and a joint Markov Logic Network (MLN). We show the effectiveness of these models on a biomedical event corpus. Both models outperform the systems that do not use coreference information. When the two proposed models are compared to each other, joint MLN outperforms pipeline SVM with gold coreference information