The optic tectum (called superior colliculus in mammals) is critical for eye-head gaze shifts as we navigate in the terrain and need to adapt our movements to the visual scene. The neuronal mechanisms underlying the tectal contribution to stimulus selection and gaze reorientation remains, however, unclear at the microcircuit level. To analyze this complex-yet phylogenetically conservedsensorimotor system, we developed a novel in vitro preparation in the lamprey that maintains the eye and midbrain intact and allows for whole-cell recordings from prelabeled tectal gaze-controlling cells in the deep layer, while visual stimuli are delivered. We found that receptive field activation of these cells provide monosynaptic retinal excitation followed by local GABAergic inhibition (feedforward). The entire remaining retina, on the other hand, elicits only inhibition (surround inhibition). If two stimuli are delivered simultaneously, one inside and one outside the receptive field, the former excitatory response is suppressed. When local inhibition is pharmacologically blocked, the suppression induced by competing stimuli is canceled. We suggest that this rivalry between visual areas across the tectal map is triggered through long-range inhibitory tectal connections. Selection commands conveyed via gazecontrolling neurons in the optic tectum are, thus, formed through synaptic integration of local retinotopic excitation and global tectal inhibition. We anticipate that this mechanism not only exists in lamprey but is also conserved throughout vertebrate evolution.optic tectum | superior colliculus | GABAergic inhibition | gaze control | evolution V isual scenes are composed of abundant stimuli, and the gaze needs continuously to be redirected toward different objectsan important task for the brain. Current models postulate that stimulus selection occurs through a process involving competitive interaction between different visual stimuli, resulting in the appropriate eye-head movement (1-5). The optic tectum (superior colliculus in mammals) has a causal role in the stimulus selection process (6-12) and not only in the control of saccades and eyehead gaze shifts (13-16). Although the collicular contribution to the selection process is of central importance, the underlying neuronal processes have remained elusive due to methodological limitations. It is our aim here to address this issue in a novel experimental model.The optic tectum is well developed in the lamprey, belonging to the oldest extant vertebrate group that evolved 560 million years ago (17), and it has remained conserved throughout vertebrate phylogeny (18)(19)(20)(21)(22). Afferents from retina provide a direct input to the superficial layers of the optic tectum, where a retinotopic map is formed (23-26). The intermediate and deep layers give rise to projections to brainstem areas and a motor map is formed that is responsible for the coordination of eye, head, and body movements (22,(27)(28)(29).To uncover the mechanisms underlying visual stimulus selection for gaz...

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. The GPh neurons are glutamatergic and can drive the activity of the lateral habenula, which, in turn, provides an indirect inhibitory influence on midbrain dopamine neurons. We show that GPh neurons receive inhibitory input from the striosomal compartment of the striatum. The striosomal input can reduce the excitatory drive to the lateral habenula and, consequently, decrease the inhibition onto the dopaminergic system. Dopaminergic neurons, in turn, provide feedback that inhibits the GPh. In addition, GPh neurons receive direct projections from the pallium (cortex in mammals), which can increase the GPh activity to drive the lateral habenula to increase the inhibition of the neuromodulatory systems. This circuitry, thus, differs markedly from the "direct" and "indirect" pathways that regulate the pallidal (e.g., globus pallidus) output nuclei involved in the control of motion. Our results show that a distinct reward-evaluation circuit exists within the basal ganglia, in parallel to the direct and indirect pathways, which select actions. Our results suggest that these circuits are part of the fundamental blueprint that all vertebrates use to select actions and evaluate their outcome.striosomes | reward/aversion | pallium/cortex | evolution T o achieve a goal, animals need to select actions and evaluate their outcome to determine whether their goal was achieved. In mammals, the basal ganglia play a key role in the selection of actions (1-3) and have more recently been suggested to additionally contribute to predicting and evaluating the outcome of the selected actions (4-8).The so-called "direct" and "indirect" pathways through the basal ganglia are present in all vertebrates and act together to select actions by decreasing tonic inhibition of the basal ganglia output nuclei [globus pallidus interna (GPi) and substantia nigra pars reticulata (SNr)] on a selected motor program and increasing the inhibition onto other competing actions. The output of these selection circuits target brainstem and thalamic motor areas, and neurons within this circuit are modulated by various aspect of movement kinetics related to the initiation and modulation of ongoing actions.In addition to the output neurons that project to motor areas, a separate subpopulation of pallidal neurons projects to the lateral habenula (9-12), a structure involved in evaluating and predicting the motivational value of actions. Recent in vivo recordings in primates have shown that the activity of these habenula-projecting pallidal neurons is modulated by the cues that predict the availability of reward (13,14) and not by aspects of movements. The majority of these pallidal neurons, as with latera...

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.

Dopamine neurons in the SNc play a pivotal role in modulating motor behavior via striatum. Here, we show that the same dopamine neuron that targets striatum also sends a direct branch to the optic tectum (superior colliculus). Whenever SNc neurons are activated, both targets will therefore be affected. Visual stimuli (looming or bars) activate the dopamine neurons coding saliency and also elicit distinct motor responses mediated via tectum (eye, orienting or evasive), which are modulated by the dopamine input. Whole-cell recordings from tectal projection neurons and interneurons show that dopamine, released by SNc stimulation, increases or decreases the excitability depending on whether they express the dopamine D1 or the D2 receptor. SNc thus exerts its effects on the visuomotor system through a combined effect directly on tectum and also via striatum. This direct SNc modulation will occur regardless of striatum and represents a novel mode of motor control.

Animals integrate the different senses to facilitate event-detection for navigation in their environment. In vertebrates, the optic tectum (superior colliculus) commands gaze shifts by synaptic integration of different sensory modalities. Recent works suggest that tectum can elaborate gaze reorientation commands on its own, rather than merely acting as a relay from upstream/forebrain circuits to downstream premotor centers. We show that tectal circuits can perform multisensory computations independently and, hence, configure final motor commands. Single tectal neurons receive converging visual and electrosensory inputs, as investigated in the lamprey - a phylogenetically conserved vertebrate. When these two sensory inputs overlap in space and time, response enhancement of output neurons occurs locally in the tectum, whereas surrounding areas and temporally misaligned inputs are inhibited. Retinal and electrosensory afferents elicit local monosynaptic excitation, quickly followed by inhibition via recruitment of GABAergic interneurons. Multisensory inputs can thus regulate event-detection within tectum through local inhibition without forebrain control.DOI: http://dx.doi.org/10.7554/eLife.16472.001