During an auditory discrimination task in rats, synaptic inputs representing either high or low sound frequencies from the cortex to the striatum are specifically strengthened, depending on reward contingencies. Much research has been aimed at dissecting the neural circuitry underlying perceptual decision making, but how our perception of the environment and sensory input is transformed into action is unclear. Anthony Zador and colleagues find that during an auditory discrimination task in mice, synaptic inputs representing either high or low sound frequencies from the cortex to the striatum are specifically strengthened, depending on reward contingencies. The authors speculate that selective strengthening of appropriate corticostriatal synapses during learning may allow animals to categorize a variety of sensory stimuli and may reflect a general mechanism through which sensory representations guide the selection of motor responses. Perceptual decisions are based on the activity of sensory cortical neurons, but how organisms learn to transform this activity into appropriate actions remains unknown. Projections from the auditory cortex to the auditory striatum carry information that drives decisions in an auditory frequency discrimination task1. To assess the role of these projections in learning, we developed a channelrhodopsin-2-based assay to probe selectively for synaptic plasticity associated with corticostriatal neurons representing different frequencies. Here we report that learning this auditory discrimination preferentially potentiates corticostriatal synapses from neurons representing either high or low frequencies, depending on reward contingencies. We observe frequency-dependent corticostriatal potentiation in vivo over the course of training, and in vitro in striatal brain slices. Our findings suggest a model in which the corticostriatal synapses made by neurons tuned to different features of the sound are selectively potentiated to enable the learned transformation of sound into action.

The dorsal striatum has emerged as a key region in sensory-guided, reward-driven decision making. A posterior sub-region of the dorsal striatum, the auditory striatum, receives convergent projections from both auditory thalamus and auditory cortex. How these pathways contribute to auditory striatal activity and function remains largely unknown. Here we show that chemogenetic inhibition of the projections from either the medial geniculate body (MGB) or primary auditory cortex (ACx) to auditory striatum in mice impairs performance in an auditory frequency discrimination task. While recording striatal sound responses, we find that transiently silencing the MGB projection reduced sound responses across a wide-range of frequencies in striatal medium spiny neurons. In contrast, transiently silencing the primary ACx projection diminish sound responses preferentially at the best frequencies in striatal medium spiny neurons. Together, our findings reveal that the MGB projection mainly functions as a gain controller, whereas the primary ACx projection provides tuning information for striatal sound representations.

Microglia are important for brain homeostasis and immunity, but their role in regulating vigilance remains unclear. We employed genetic, physiological, and metabolomic methods to examine microglial involvement in the regulation of wakefulness and sleep. Microglial depletion decreased stable nighttime wakefulness in mice by increasing transitions between wakefulness and non-rapid eye movement (NREM) sleep. Metabolomic analysis revealed that the sleep-wake behavior closely correlated with diurnal variation of the brain ceramide, which disappeared in microglia-depleted mice. Ceramide preferentially influenced microglia in the thalamic reticular nucleus (TRN), and local depletion of TRN microglia produced similar impaired wakefulness. Chemogenetic manipulations of anterior TRN neurons showed that they regulated transitions between wakefulness and NREM sleep. Their firing capacity was suppressed by both microglial depletion and added ceramide. In microglia-depleted mice, activating anterior TRN neurons or inhibiting ceramide production both restored stable wakefulness. These findings demonstrate that microglia can modulate stable wakefulness through anterior TRN neurons via ceramide signaling.

Dopamine (DA) is a behaviorally and clinically diverse neuromodulator that controls CNS function. DA plays major roles in many behaviors including locomotion, learning, habit formation, perception, and memory processing. Reflecting this, DA dysregulation produces a wide variety of cognitive symptoms seen in neuropsychiatric diseases such as Parkinson’s, Schizophrenia, addiction, and Alzheimer’s disease. Here, we review recent advances in the DA systems neuroscience field and explore the advancing hypothesis that DA’s behavioral function is linked to disease deficits in a neural circuit-dependent manner. We survey different brain areas including the basal ganglia’s dorsomedial/dorsolateral striatum, the ventral striatum, the auditory striatum, and the hippocampus in rodent models. Each of these regions have different reported functions and, correspondingly, DA’s reflecting role in each of these regions also has support for being different. We then focus on DA dysregulation states in Parkinson’s disease, addiction, and Alzheimer’s Disease, emphasizing how these afflictions are linked to different DA pathways. We draw upon ideas such as selective vulnerability and region-dependent physiology. These bodies of work suggest that different channels of DA may be dysregulated in different sets of disease. While these are great advances, the fine and definitive segregation of such pathways in behavior and disease remains to be seen. Future studies will be required to define DA’s necessity and contribution to the functional plasticity of different striatal regions.