In vivo whole-cell membrane potential recordings, simultaneous monitoring and bidirectional manipulation of dopamine signaling in awake, behaving mice to examine how dopamine shapes corticostriatal circuits and identify learning related plasticity as its principal mechanism for shaping striatal circuits in vivo.
Abstract
Dopamine signaling in the striatum is essential for a wide range of functions, from reward learning to motor vigor and behavioral flexibility. Although dopamine signals fluctuate on sub-second timescales, how these signals are translated into lasting changes in striatal circuit function remains unknown. Resolving this requires cell-type-specific measurements of synaptic and intrinsic properties during behavior, a longstanding technical challenge. Here, we combined in vivo whole-cell membrane potential recordings, simultaneous monitoring and bidirectional manipulation of dopamine signaling in awake, behaving mice to examine how dopamine shapes corticostriatal circuits. Acute manipulations of dopamine over seconds to minutes produced only modest effects on corticostriatal synaptic transmission and no detectable changes in membrane potential dynamics or intrinsic excitability. By contrast, associative learning robustly strengthened identified corticostriatal synapses onto both D1- and D2-expressing spiny projection neurons, yet only D1-SPN plasticity required dopamine signaling. These findings challenge models in which dopamine acts rapidly to tune striatal excitability and identify learning related plasticity as its principal mechanism for shaping striatal circuits in vivo.
The neuromodulator dopamine is essential for voluntary movement and learning from experience. While these behaviors often occur simultaneously and rely on overlapping nigrostriatal dopamine circuits, they are also separable and can manifest independently. How a single neuromodulatory system controls such disparate aspe...
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Brain plasticity enables adaptive learning, memory, and behavior, yet it is neither unconstrained nor automatic. Emerging evidence indicates that synaptic change occurs within a hierarchy of interacting regulatory layers that collectively determine when, where, and how plasticity is expressed. We propose a four‐layer h...
Neural plasticity enables the nervous system to adapt its structure and function in response to experience. Although synaptic plasticity is a central cellular mechanism underlying learning and memory, action potential propagation along axons is also subject to plastic regulation and critically shapes neural computation...
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