The basal ganglia play an important role in decision making and selection of action primarily based on input from cortex, thalamus, and the dopamine system. Their main input structure, striatum, is central to this process. It consists of two types of projection neurons, together representing 95% of the neurons, and 5% of interneurons, among which are the cholinergic, fast-spiking, and low threshold-spiking subtypes. The membrane properties, soma–dendritic shape, and intrastriatal and extrastriatal synaptic interactions of these neurons are quite well described in the mouse, and therefore they can be simulated in sufficient detail to capture their intrinsic properties, as well as the connectivity. We focus on simulation at the striatal cellular/microcircuit level, in which the molecular/subcellular and systems levels meet. We present a nearly full-scale model of the mouse striatum using available data on synaptic connectivity, cellular morphology, and electrophysiological properties to create a microcircuit mimicking the real network. A striatal volume is populated with reconstructed neuronal morphologies with appropriate cell densities, and then we connect neurons together based on appositions between neurites as possible synapses and constrain them further with available connectivity data. Moreover, we simulate a subset of the striatum involving 10,000 neurons, with input from cortex, thalamus, and the dopamine system, as a proof of principle. Simulation at this biological scale should serve as an invaluable tool to understand the mode of operation of this complex structure. This platform will be updated with new data and expanded to simulate the entire striatum.

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. The nucleus of the tuberculum posterior, a homologue of the substantia nigra pars compacta (SNc)/ventral tegmental area (VTA) is present in lamprey, but only scarce data exist about its connectivity. Likewise, the D2 receptor is expressed in the striatum, but little is known about its localization in other brain areas. We used in situ hybridization and tracer injections, both in combination with tyrosine hydroxylase immunohistochemistry, to characterize the SNc/VTA efferent and afferent connectivity, and to relate its projection pattern with D2 receptor expression in particular. We show that most features of the dopaminergic system are highly conserved. As in mammals, the direct pallial (cortex in mammals) input and the basal ganglia connectivity with the SNc/VTA are present as part of the evaluation system, as well as input from the tectum as the evolutionary basis for salience/novelty detection. Moreover, the SNc/VTA receives sensory information from the olfactory bulbs, optic tectum, octavolateral area, and dorsal column nucleus, and it innervates, apart from the nigrostriatal pathway, several motor-related areas. This suggests that the dopaminergic system also contributes to the control of different motor centers at the brainstem level.

Amniotes, such as mammals and reptiles have vision and other senses represented in pallium, whereas anamniotes like amphibians, fish and cyclostomes (including lamprey) that diverged much earlier, were historically thought to process predominantly or even exclusively olfactory information in pallium. Here, we show here that there is a separate visual area with retinotopic representation and that somatosensory information from the head and trunk is represented in an adjacent area in the lamprey pallial cortex (lateral pallium). These cortical sensory areas flank a non-primary-sensory motor area. Both vision and somatosensation are relayed via the thalamus. These findings suggest that the basic sensorimotor representation of the mammalian neocortex, as well as the sensory thalamocortical relay had already evolved in the last common ancestor of cyclostomes and gnathostomes around 560 million years ago.The lamprey represents the oldest group of extant vertebrates 1 . It is an eel-like creature with a well-developed vision that lives a predatory parasitic life 2,3 . Here, we investigate the sensory representation (visual and somatosensory) in the lateral pallium (LPal; cortex) of lamprey, and to what degree it resembles that of mammals. The mammalian neocortex is organised into distinct sensory areas, including retinotopic visual and somatotopic somatosensory areas, as well as motor areas. This has been thought to be unique and an evolutionarily recent innovation in mammals [4][5][6][7] . The primary visual area in mammals receives input from the retina, relayed via the lateral geniculate nucleus. In addition, visual information from the superior colliculus is relayed via thalamus to neocortex 8,9 . Somatosensory information is mediated through the lemniscal input to cortical somatosensory areas via the ventral posterior nucleus of thalamus [10][11][12] .In non-mammalian amniotes (reptiles and birds), pallium receives visual, somatosensory and auditory inputs relayed via thalamus 5,6 . In turtles, the three-layered dorsal cortex has a visual representation, however, reported not to be organised in a retinotopic fashion 13 . Much less is known about the somatosensory organisation in the reptilian dorsal cortex 14 . In birds, visual

The basic architecture of the mammalian neocortex is remarkably similar across species. Pallial structures in the reptilian brain are considered amniote precursors of mammalian neocortex, whereas pallia of anamniotes ("lower" vertebrates) have been deemed largely insignificant with respect to homology. Here, we examine the cytoarchitecture of the lateral pallium in the lamprey, the phylogenetically oldest group of extant vertebrates. We reveal a three-layered structure with similar excitatory cell types as in the mammalian cortex and GABAergic interneurons. The ventral parts are sensory areas receiving monosynaptic thalamic input that can be activated from the optic nerve, whereas the dorsal parts contain motor areas with efferent projections to the brainstem, receiving oligosynaptic thalamic input. Both regions receive monosynaptic olfactory input. This three-layered "primordial" lamprey lateral pallium has evolved most features of the three-layered reptilian cortices and is thereby a precursor of the six-layered "neo" cortex with a long-standing evolutionary precedent (some 500 million years ago).

Our results demonstrate marked similarities in the efferent functional connectivity and control of motor behavior between the lamprey pallium and mammalian neocortex. Thus, the lamprey motor pallium/cortex represents an evolutionary blueprint of the corresponding mammalian system.