Summary Concrete examples of computation and implementation of cost-benefit decisions at the level of neuronal circuits are largely lacking. Such decisions are based on appetitive state, which is the integration of sensation, internal state and memory. Value-based decisions are accessible in neuronal circuitry of simple systems [1]. In one such, the predatory sea-slug Pleurobranchaea, appetite is readily quantified in behavior [2] and related to approach-avoidance decision [3]. Moreover, motor aspects of feeding and turning can be observed as fictive motor output in the isolated CNS [4,5]. Here we found that the excitation state of the feeding motor network both manifested appetitive state and controlled expression of orienting vs. avoidance. In isolated CNS’s spontaneous feeding network activity varied proportionally to donor feeding thresholds. CNS’s from low and high feeding threshold donors expressed fictive orienting or avoidance, respectively, in response to brief stimulation of sensory nerves. Artificially exciting the feeding network converted fictive avoidance to orienting. Thus, the feeding network embodied appetitive state and toggled approach-avoidance decision by configuring response symmetry of the premotor turn network. A resulting model suggests a basic cost-benefit decision module from which to consider evolutionary elaboration of the circuitry to serve more intricate valuation processes in complex animals.

Many cost-benefit decisions reduce to simple choices between approach or avoidance (or active disregard) to salient stimuli. Physiologically, critical factors in such decisions are modulators of the homeostatic neural networks that bias decision processes from moment to moment. For the predatory sea-slug Pleurobranchaea, serotonin (5-HT) is an intrinsic modulatory promoter of general arousal and feeding. We correlated 5-HT actions on appetitive state with its effects on the approach-avoidance decision in Pleurobranchaea. 5-HT and its precursor 5-hydroxytryptophan (5-HTP) augmented general arousal state and reduced feeding thresholds in intact animals. Moreover, 5-HT switched the turn response to chemosensory stimulation from avoidance to orienting in many animals. In isolated CNSs, bath application of 5-HT both stimulated activity in the feeding motor network and switched the fictive turn response to unilateral sensory nerve stimulation from avoidance to orienting. Previously, it was shown that increasing excitation state of the feeding network reversibly switched the turn motor network response from avoidance to orienting, and that 5-HT levels vary inversely with nutritional state. A simple model posits a critical role for 5-HT in control of the turn network response by corollary output of the feeding network. In it, 5-HT acts as an intrinsic neuromodulatory factor coupled to nutritional status and regulates approach-avoidance via the excitation state of the feeding network. Thus, the neuromodulator is a key organizing element in behavioral choice of approach or avoidance through its actions in promoting appetitive state, in large part via the homeostatic feeding network.

A simple circuit for cost-benefit decision derived from behavioral and neural studies of the predatory sea-slug Pleurobranchaea may closely resemble that upon which the more complex valuation and decision processes of the social vertebrates are built. The neuronal natures of the pathways in the connectionist model comprise classic central pattern generators, bipolar switch mechanisms, and neuromodulatory state regulation. Marked potential exists for exploring more complex neuroeconomic behavior by appending appropriate circuitry in simulo.

Left–right asymmetry is a fundamental feature of higher-order brain structure; however, the molecular basis of brain asymmetry remains unclear. We recently identified structural and functional asymmetries in mouse hippocampal circuitry that result from the asymmetrical distribution of two distinct populations of pyramidal cell synapses that differ in the density of the NMDA receptor subunit GluRε2 (also known as NR2B, GRIN2B or GluN2B). By examining the synaptic distribution of ε2 subunits, we previously found that β2-microglobulin-deficient mice, which lack cell surface expression of the vast majority of major histocompatibility complex class I (MHCI) proteins, do not exhibit circuit asymmetry. In the present study, we conducted electrophysiological and anatomical analyses on the hippocampal circuitry of mice with a knockout of the paired immunoglobulin-like receptor B (PirB), an MHCI receptor. As in β2-microglobulin-deficient mice, the PirB-deficient hippocampus lacked circuit asymmetries. This finding that MHCI loss-of-function mice and PirB knockout mice have identical phenotypes suggests that MHCI signals that produce hippocampal asymmetries are transduced through PirB. Our results provide evidence for a critical role of the MHCI/PirB signaling system in the generation of asymmetries in hippocampal circuitry.