Highlights d Striatal MSNs release GABA to activate astrocyte Gi-coupled GABA B receptors d Astrocyte Gi pathway activation results in hyperactivity with disrupted attention d Astrocyte Gi pathway activation increases fast synaptic excitation and MSN firing d Behavioral and synaptic effects are due to reactivation of TSP1 in astrocytes
Midbrain dopamine (DA) neurons encode both reward and movement-related events, and are implicated in disorders of reward processing as well as movement. Consequently, disentangling the contribution of DA neurons in reinforcing versus generating movements is challenging and has led to lasting controversy. We dissociated these functions by parametrically varying the timing of optogenetic manipulations in a Pavlovian conditioning task, and examining the influence on anticipatory licking prior to reward delivery. Inhibiting both ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) DA neurons in the post-reward period had a significantly greater behavioral effect than inhibition in the pre-reward period of the task. Furthermore, the contribution of DA neurons to behavior decreased linearly as a function of elapsed time after reward. Together, the results indicate a temporally restricted role of DA neurons primarily related to reinforcing stimulus-reward associations, and suggest that directly generating movements is a comparatively less important function.
Visual cortical neurons encode the position and motion direction of specific stimuli retrospectively, without any locomotion or task demand 1 . Hippocampus, a part of visual system, is hypothesized to require self-motion or cognitive task to generate allocentric spatial selectivity that is scalar, abstract 2,3 , and prospective 4-7 . To bridge these seeming disparities, we measured rodent hippocampal selectivity to a moving bar of light in a body-fixed rat. About 70% of dorsal CA1 neurons showed stable activity modulation as a function of the bar's angular position, independent of behavior and rewards. A third of tuned cells also encoded the direction of revolution. In other experiments, neurons encoded the distance of bar, with preference for approaching motion. Collectively, these demonstrate visually evoked vectorial selectivity (VEVS). Unlike place cells, VEVS was retrospective. Changes in the visual stimulus or its trajectory did not cause remapping but only caused gradual changes. Most VEVS tuned neurons behaved like place cells during spatial exploration and the two selectivity were correlated. Thus, VEVS could form the basic building block of hippocampal activity. When combined with self-motion, reward, or multisensory stimuli 8 , it can generate the complexity of prospective representations including allocentric space 9 , time 10,11 , and episodes 12 .
Visual cortical neurons encode the position and motion direction of specific stimuli retrospectively, without any locomotion or task demand. Hippocampus, a part of visual system, is hypothesized to require self-motion or cognitive task to generate allocentric spatial selectivity that is scalar, abstract, and prospective. To bridge these seeming disparities, we measured rodent hippocampal selectivity to a moving bar of light in a body-fixed rat. About 70% of dorsal CA1 neurons showed stable activity modulation as a function of the bar angular position, independent of behavior and rewards. A third of tuned cells also encoded the direction of revolution. In other experiments, neurons encoded the distance of the bar, with preference for approaching motion. Collectively, these demonstrate visually evoked vectorial selectivity (VEVS). Unlike place cells, VEVS was retrospective. Changes in the visual stimulus or its trajectory did not cause remapping but only caused gradual changes. Most VEVS-tuned neurons behaved like place cells during spatial exploration and the two selectivities were correlated. Thus, VEVS could form the basic building block of hippocampal activity. When combined with self-motion, reward, or multisensory stimuli, it can generate the complexity of prospective representations including allocentric space, time, and episodes.
Targeting neurons with light-driven opsins is widely used to investigate cell-specific responses. We transfected midbrain dopamine neurons with the excitatory opsin Chrimson. Extracellular basal and stimulated neurotransmitter levels in the dorsal striatum were measured by microdialysis in awake mice. Optical activation of dopamine cell bodies evoked terminal dopamine release in the striatum. Multiplexed analysis of dialysate samples revealed that the evoked dopamine was accompanied by temporally coupled increases in striatal 3-methoxytyramine, an extracellular dopamine metabolite, and in serotonin. We investigated a mechanism for dopamine−serotonin interactions involving striatal dopamine receptors. However, the evoked serotonin associated with optical stimulation of dopamine neurons was not abolished by striatal D1-or D2-like receptor inhibition. Although the mechanisms underlying the coupling of striatal dopamine and serotonin remain unclear, these findings illustrate advantages of multiplexed measurements for uncovering functional interactions between neurotransmitter systems. Furthermore, they suggest that the output of optogenetic manipulations may extend beyond opsin-expressing neuronal populations.
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