Efficient foraging requires an ability to coordinate discrete reward-seeking and reward-retrieval behaviors. We used pathway-specific chemogenetic inhibition to investigate how rats' mesolimbic and mesocortical dopamine circuits contribute to the expression and modulation of reward seeking and retrieval. Inhibiting ventral tegmental area dopamine neurons disrupted the tendency for reward-paired cues to motivate reward seeking, but spared their ability to increase attempts to retrieve reward. Similar effects were produced by inhibiting dopamine inputs to nucleus accumbens, but not medial prefrontal cortex. Inhibiting dopamine neurons spared the suppressive effect of reward devaluation on reward seeking, an assay of goal-directed behavior. Attempts to retrieve reward persisted after devaluation, indicating they were habitually performed as part of a fixed action sequence. Our findings show that complete bouts of reward seeking and retrieval are behaviorally and neurally dissociable from bouts of reward seeking without retrieval. This dichotomy may prove useful for uncovering mechanisms of maladaptive behavior.
All data generated and analyzed during this study are included in supporting files. Source data files have been provided for Figures 1, 3, 4 and 5, as well as their respective supplemental figures.
- Kate M Wassum
- Sean B Ostlund
- Sean B Ostlund
- Sean B Ostlund
- Sean B Ostlund
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All experimental procedures that involved rats were approved by the UC Irvine Institutional Animal Care and Use Committee (protocol AUP-17-68) and were in accordance with the National Research Council Guide for the Care and Use of Laboratory Animals.
- Naoshige Uchida, Harvard University, United States
© 2019, Halbout et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
The presynaptic protein α-synuclein (αSyn) has been suggested to be involved in the pathogenesis of Parkinson’s disease (PD). In PD, the amygdala is prone to develop insoluble αSyn aggregates, and it has been suggested that circuit dysfunction involving the amygdala contributes to the psychiatric symptoms. Yet, how αSyn aggregates affect amygdala function is unknown. In this study, we examined αSyn in glutamatergic axon terminals and the impact of its aggregation on glutamatergic transmission in the basolateral amygdala (BLA). We found that αSyn is primarily present in the vesicular glutamate transporter 1-expressing (vGluT1+) terminals in mouse BLA, which is consistent with higher levels of αSyn expression in vGluT1+ glutamatergic neurons in the cerebral cortex relative to the vGluT2+ glutamatergic neurons in the thalamus. We found that αSyn aggregation selectively decreased the cortico-BLA, but not the thalamo-BLA, transmission; and that cortico-BLA synapses displayed enhanced short-term depression upon repetitive stimulation. In addition, using confocal microscopy, we found that vGluT1+ axon terminals exhibited decreased levels of soluble αSyn, which suggests that lower levels of soluble αSyn might underlie the enhanced short-term depression of cortico-BLA synapses. In agreement with this idea, we found that cortico-BLA synaptic depression was also enhanced in αSyn knockout mice. In conclusion, both basal and dynamic cortico-BLA transmission were disrupted by abnormal aggregation of αSyn and these changes might be relevant to the perturbed cortical control of the amygdala that has been suggested to play a role in psychiatric symptoms in PD.
Animals can evolve dramatic sensory functions in response to environmental constraints, but little is known about the neural mechanisms underlying these changes. The Mexican tetra, Astyanax mexicanus, is a leading model to study genetic, behavioral, and physiological evolution by comparing eyed surface populations and blind cave populations. We compared neurophysiological responses of posterior lateral line afferent neurons and motor neurons across A. mexicanus populations to reveal how shifts in sensory function may shape behavioral diversity. These studies indicate differences in intrinsic afferent signaling and gain control across populations. Elevated endogenous afferent activity identified a lower response threshold in the lateral line of blind cavefish relative to surface fish leading to increased evoked potentials during hair cell deflection in cavefish. We next measured the effect of inhibitory corollary discharges from hindbrain efferent neurons onto afferents during locomotion. We discovered that three independently derived cavefish populations have evolved persistent afferent activity during locomotion, suggesting for the first time that partial loss of function in the efferent system can be an evolutionary mechanism for neural adaptation of a vertebrate sensory system.