Neural Networks With Motivation.

Animals rely on internal motivational states to make decisions. The role of motivational salience in decision making is in early stages of mathematical understanding. Here, we propose a reinforcement learning framework that relies on neural networks to learn optimal ongoing behavior for dynamically changing motivation values.

Opposing Contributions of GABAergic and Glutamatergic Ventral Pallidal Neurons to Motivational Behaviors.

The ventral pallidum (VP) is critical for invigorating reward seeking and is also involved in punishment avoidance, but how it contributes to such opposing behavioral actions remains unclear. Here, we show that GABAergic and glutamatergic VP neurons selectively control behavior in opposing motivational contexts. In vivo recording combined with optogenetics in mice revealed that these two populations oppositely encode positive and negative motivational value, are differentially modulated by animal's internal state, and determine the behavioral response during motivational conflict.

The Lateral Habenula Circuitry: Reward Processing and Cognitive Control.

There has been a growing interest in understanding the role of the lateral habenula (LHb) in reward processing, affect regulation, and goal-directed behaviors. The LHb gets major inputs from the habenula-projecting globus pallidus and the mPFC, sending its efferents to the dopaminergic VTA and SNc, serotonergic dorsal raphe nuclei, and the GABAergic rostromedial tegmental nucleus. Recent studies have made advances in our understanding of the LHb circuit organization, yet the precise mechanisms of its involvement in complex behaviors are largely unknown.

A basal ganglia circuit for evaluating action outcomes.

The basal ganglia, a group of subcortical nuclei, play a crucial role in decision-making by selecting actions and evaluating their outcomes. While much is known about the function of the basal ganglia circuitry in selection, how these nuclei contribute to outcome evaluation is less clear. Here we show that neurons in the habenula-projecting globus pallidus (GPh) in mice are essential for evaluating action outcomes and are regulated by a specific set of inputs from the basal ganglia.

The lamprey blueprint of the mammalian nervous system.

The basic features of the vertebrate nervous system are conserved throughout vertebrate phylogeny to a much higher degree than previously thought. In this mini-review, we show that not only the organization of the different motor programs underlying eye, orienting, locomotor, and respiratory movements are similarly organized, but also that the basic structure of the forebrain engaged in the control of movement is conserved. In the lamprey, which diverged already 560 million years ago from the vertebrate line of evolution leading up to primates, the basic components of the basal ganglia are similar to those of mammals in considerable detail.

Evolutionarily conserved organization of the dopaminergic system in lamprey: SNc/VTA afferent and efferent connectivity and D2 receptor expression.

The dopaminergic system influences motor behavior, signals reward and novelty, and is an essential component of the basal ganglia in all vertebrates including the lamprey, one of the phylogenetically oldest vertebrates. The intrinsic organization and function of the lamprey basal ganglia is highly conserved. For instance, the direct and indirect pathways are modulated through dopamine D1 and D2 receptors in lamprey and in mammals.

Independent circuits in the basal ganglia for the evaluation and selection of actions.

The basal ganglia are critical for selecting actions and evaluating their outcome. Although the circuitry for selection is well understood, how these nuclei evaluate the outcome of actions is unknown. Here, we show in lamprey that a separate evaluation circuit, which regulates the habenula-projecting globus pallidus (GPh) neurons, exists within the basal ganglia.

Dopamine differentially modulates the excitability of striatal neurons of the direct and indirect pathways in lamprey.

The functions of the basal ganglia are critically dependent on dopamine. In mammals, dopamine differentially modulates the excitability of the direct and indirect striatal projection neurons, and these populations selectively express dopamine D1 and D2 receptors, respectively. Although the detailed organization of the basal ganglia is conserved throughout the vertebrate phylum, it was unknown whether the differential dopamine modulation of the direct and indirect pathways is present in non-mammalian species.

The evolutionary origin of the vertebrate basal ganglia and its role in action selection.

The group of nuclei within the basal ganglia of the forebrain is central to the control of movement. We present data showing that the structure and function of the basal ganglia have been conserved throughout vertebrate evolution over some 560 million years. The interaction between the different nuclei within the basal ganglia is conserved as well as the cellular and synaptic properties and transmitters.

Evolutionarily conserved differences in pallial and thalamic short-term synaptic plasticity in striatum.

The striatum of the basal ganglia is conserved throughout the vertebrate phylum. Tracing studies in lamprey have shown that its afferent inputs are organized in a manner similar to that of mammals. The main inputs arise from the thalamus (Th) and lateral pallium (LPal; the homologue of cortex) that represents the two principal excitatory glutamatergic inputs in mammals.

The dopamine D2 receptor gene in lamprey, its expression in the striatum and cellular effects of D2 receptor activation.

All basal ganglia subnuclei have recently been identified in lampreys, the phylogenetically oldest group of vertebrates. Furthermore, the interconnectivity of these nuclei is similar to mammals and tyrosine hydroxylase-positive (dopaminergic) fibers have been detected within the input layer, the striatum. Striatal processing is critically dependent on the interplay with the dopamine system, and we explore here whether D2 receptors are expressed in the lamprey striatum and their potential role.

Evolution of the basal ganglia: dual-output pathways conserved throughout vertebrate phylogeny.

The basal ganglia, including the striatum, globus pallidus interna and externa (GPe), subthalamic nucleus (STN), and substantia nigra pars compacta, are conserved throughout vertebrate phylogeny and have been suggested to form a common vertebrate mechanism for action selection. In mammals, this circuitry is further elaborated by the presence of a dual-output nucleus, the substantia nigra pars reticulata (SNr), and the presence of modulatory input from the cholinergic pedunculopontine nucleus (PPN). We sought to determine whether these additional components of the mammalian basal ganglia are also present in one of the phylogenetically oldest vertebrates, the lamprey.

Evolutionary conservation of the habenular nuclei and their circuitry controlling the dopamine and 5-hydroxytryptophan (5-HT) systems.

The medial (MHb) and lateral (LHb) habenulae are a small group of nuclei that regulate the activity of monoaminergic neurons. Disruptions to these nuclei lead to deficits in a range of cognitive and motor functions from sleep to decision making. Interestingly, the habenular nuclei are present in all vertebrates, suggesting that they provide a common neural mechanism to influence these diverse functions.

Evolutionary conservation of the basal ganglia as a common vertebrate mechanism for action selection.

Background: Although the basal ganglia are thought to play a key role in action selection in mammals, it is unknown whether this mammalian circuitry is present in lower vertebrates as a conserved selection mechanism. We aim here, using lamprey, to elucidate the basal ganglia circuitry in the phylogenetically oldest group of vertebrates (cyclostomes) and determine how this selection architecture evolved to accommodate the increased behavioral repertoires of advanced vertebrates.

Results: We show, using immunohistochemistry, tract tracing, and whole-cell recordings, that all parts of the mammalian basal ganglia (striatum, globus pallidus interna [GPi] and externa [GPe], and subthalamic nucleus [STN]) are present in the lamprey forebrain.