Acetylcholine (ACh) signaling in the basolateral amygdala (BLA) has been implicated in salience-related processing and associative learning, yet the circuit mechanisms that regulate its dynamics remain poorly understood. Here we show that BLA ACh dynamically represented salience. In the mouse nucleus accumbens (NAc), D1-expressing medium spiny neurons (MSNs) selectively promote, whereas D2-expressing MSNs selectively suppress, ACh release in the BLA but not in the cortex or hippocampus. NAc D1 and D2 MSNs regulate BLA ACh by disinhibiting and inhibiting cholinergic neurons in the substantia innominata (SI), respectively. Axon terminals of D1 and D2 MSNs in the SI exhibit differential responses to salient stimuli and modulate BLA ACh dynamics. Closed-loop optogenetic manipulations of NAc D1 and D2 projections to the SI have opposing effects on associative learning. Our findings uncover an unconventional role of striatal MSNs in modulating behavioral significance through the regulation of salience-related amygdalar ACh activity.

Everyday decisions depend on linking sensory stimuli with actions and outcomes. The striatum supports these sensorimotor associations through dopamine-dependent plasticity. Thus, the timing and magnitude of dopamine release is critical for learning. Recent work has characterized a local striatal microcircuit in which cholinergic interneurons (CINs) modulate dopamine release via acetylcholine activation of nicotinic receptors on dopamine axons. Here, we show that visual stimuli evoke dopamine responses in the dorsomedial striatum through this cholinergic-dependent mechanism. Using anatomical and functional methods to identify which pathways elicit these signals, we found that primary visual cortex and early sensory areas that project to the striatum exhibited only weak connectivity to CINs, despite robust connectivity to projection neurons, and were unable to drive dopamine release. In contrast, frontal cortical regions, including the prelimbic and anterior cingulate cortices, strongly recruited CINs and acetylcholine, producing robust dopamine release both and . These findings reveal a fundamental distinction between sensory and frontal cortical inputs to the striatum, demonstrating that only the latter provide effective access to cholinergic-dependent dopamine signaling. This work establishes a framework for understanding how cortical circuits shape striatal dopamine to support reinforcement learning.

The striatum is a major cortical input site of the basal ganglia and plays a critical role in the control of orofacial movements such as licking. However, how striatal activity relates to the spatial features of licking behavior remains unclear. In this study, we examined whether neural activity in the striatal matrix and striosomal compartments is associated with the spatial position of a licking target during an operant task. Head-fixed male mice performed a licking task in which the target positions were varied across three spatial dimensions. Using fiber photometry in Calb1-IRES-Cre (n = 7) and Pdyn-IRES-Cre (n = 6) mice, we recorded calcium signals from matrix and striosomal neurons. Associations between neural activity, target position, and behavioral variables were quantified using linear mixed-effects modeling with cross-validation. Matrix activity prior to the first detected lick was associated with reaction time and the dorsal-ventral target position. During licking, matrix activity was associated with the anterior-posterior and medial-lateral positions, independent of reaction time and lick count, whereas striosomal activity was associated with the dorsal-ventral position. These associations were correlational and differed in strength. The association between matrix activity and the anterior-posterior and medial-lateral positions was the most robust. The present findings are limited to male mice and to the hemisphere ipsilateral to the spout.

Recent advances in the field of Voltage Imaging, with a special focus on new constructs and novel implementations.

Basal Ganglia Advances is a collection highlighting research on the structure, function, and disorders of the basal ganglia. It features studies spanning neuroscience, clinical insights, and computational models, serving as a hub for advances in movement, cognition, and behavior.

Work related to place tuning, spatial navigation, orientation and direction. Mainly includes articles on connectivity in the hippocampus, retrosplenial cortex, and related areas.

The striatum is a major cortical input site of the basal ganglia and plays a critical role in the control of orofacial movements such as licking. However, how striatal activity relates to the spatial features of licking behavior remains unclear. In this study, we examined whether neural activity in the striatal matrix and striosomal compartments is associated with the spatial position of a licking target during an operant task. Head-fixed male mice performed a licking task in which the target positions were varied across three spatial dimensions. Using fiber photometry in Calb1-IRES-Cre (n = 7) and Pdyn-IRES-Cre (n = 6) mice, we recorded calcium signals from matrix and striosomal neurons. Associations between neural activity, target position, and behavioral variables were quantified using linear mixed-effects modeling with cross-validation. Matrix activity prior to the first detected lick was associated with reaction time and the dorsal-ventral target position. During licking, matrix activity was associated with the anterior-posterior and medial-lateral positions, independent of reaction time and lick count, whereas striosomal activity was associated with the dorsal-ventral position. These associations were correlational and differed in strength. The association between matrix activity and the anterior-posterior and medial-lateral positions was the most robust. The present findings are limited to male mice and to the hemisphere ipsilateral to the spout.

Neurons interact in networks distributed throughout the brain. While much effort has focused on whole-brain calcium imaging, advances in genetically encoded voltage indicators raise the question of whether it might be possible to image neuronal voltage across entire brains. Achieving this requires a microscope with high volumetric imaging rates and signal-to-noise ratio. Here we present a remote-scanning light-sheet microscope capable of imaging genetically encoded voltage indicator-expressing neurons distributed throughout much of the brain of larval zebrafish at a volumetric rate of 200.8 Hz. We measured voltage traces from approximately one-quarter of all brain neurons. We found that neurons firing at different times during a sequence occupied different locations: visually evoked sequences mapped across the optic tectum, whereas stimulus-independent bursts were mapped across the cerebellum and medulla. Imaging voltage of neurons distributed in many brain regions may open new frontiers for understanding fundamental neural system operations.

The integration of synaptic inputs is a fundamental function of neurons. In the traditional model, excitatory inputs are summed at the soma to generate action potentials. However, how synaptic inputs are integrated by dendrites in vivo remains poorly explored. We used intravital two-photon dendritic imaging with a genetically encoded voltage indicator (accelerated sensor of action potentials 5) together with somatic whole-cell patch clamp recordings to investigate how synaptic depolarizations are transferred to the soma in pyramidal neurons of the mouse somatosensory cortex. We studied the integration of synaptic inputs under spontaneous and sensory-evoked conditions, as well as following electrical and optogenetic stimulation. In all cases, while multiple inputs evoked measurable depolarizations in the cell body, isolated synaptic potentials were strongly attenuated. Our results suggest that isolated synaptic inputs have a minimal contribution to somatic depolarization, whereas coincident inputs within short temporal windows are more effective, indicating a regime of dendritic integration that favors coincident or clustered neuronal activity in cortical networks.