Making appropriate decisions relies on the brain's capacity to evaluate the expected outcomes of available options and select the most rewarding action. The ventral striatum and midbrain dopamine neurons have been implicated in the option valuation process, consistent with the brain's reinforcement learning theory in which these brain structures encode and update value representations of expected outcomes. Extending beyond this framework, we found that the dopamine-ventral striatum system plays a more proactive role in action selection. We recorded single-unit activity from ventral striatum neurons in macaque monkeys as they sequentially evaluated an option, decided whether to perform an action to choose it, and expressed that motor action. The activity of these neurons initially reflected the value of the option but gradually shifted to reflect monkey's action selection, as if the ventral striatum translates the value information into the action. Moreover, optogenetic facilitation of dopamine input to the ventral striatum as well as electrical stimulation of this region altered monkey's action selection. Our findings reveal a previously unappreciated function of the ventral striatum as a neural hub that bridges option valuation and action selection, and demonstrate the contribution of dopamine in the process leading to action selection within this region.

The striatum comprises a network characterized by a highly shared feedforward inhibition (FFI) mediated by fast-spiking interneurons (FSI), which constitute only 1% of the striatal population. We investigated the dynamical consequences of this extensively shared FFI beyond inducing synchrony in a local striatal microcircuit. Our findings reveal that increased FFI sharing enhances the across-trial variability of striatal responses, activity of medium spiny neurons (MSNs), to cortical inputs, and endows the striatal network with the capacity to modulate output correlations in a bidirectional manner. Specifically, weakly shared cortical inputs become more correlated, whereas strongly shared cortical inputs are decorrelated in the presence of FSIs. These dynamic modulatory effects on MSNs, in turn, substantially alter the spiking statistics of downstream neurons in the globus pallidus, regarding across-trial variability and burstiness.

Parkinson's disease (PD) is a movement disorder caused by the loss of dopaminergic innervation, particularly to the striatum. PD patients often exhibit sensory impairments, yet the underlying network mechanisms are unknown. Here we examined how dopamine (DA) depletion affects sensory processing in the mouse striatum. We used the optopatcher for online identification of direct and indirect pathway projection neurons (MSNs) during in vivo whole-cell recordings. In control mice, MSNs encoded the laterality of sensory inputs with larger and earlier responses to contralateral than ipsilateral whisker deflection. This laterality coding was lost in DA-depleted mice due to adaptive changes in the intrinsic and synaptic properties, mainly, of direct pathway MSNs. L-DOPA treatment restored laterality coding by increasing the separation between ipsilateral and contralateral responses. Our results show that DA depletion impairs bilateral tactile acuity in a pathway-dependent manner, thus providing unexpected insights into the network mechanisms underlying sensory deficits in PD. VIDEO ABSTRACT.

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

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

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.

Advances in optical techniques and two-photon (2P) sensitive genetic voltage indicators (GEVIs) enabled in-depth voltage imaging at single-spike and single-cell resolution. These results were achieved using ASAP-type sensors, while rhodopsin-based GEVIs were mainly used with one-photon (1P) illumination. Here, we demonstrate compatibility of rhodopsin-based GEVIs with 2P illumination. We rationally engineer a fully genetically encoded, rhodopsin-based GEVI, just another voltage indicating sensor (Jarvis), and demonstrate its utility under 1P and 2P illumination. We further show 2P usability of the fluorescence resonance energy transfer (FRET)-opsin GEVIs pAce and Voltron2. Comparing 2P scanless with fast 2P scanning illumination revealed that responses are resolved with both approaches, but FRET-opsin GEVIs show improved signal-to-noise ratio (SNR) with low irradiance, inherent to scanless illumination. Utilizing Jarvis and pAce, we establish high-SNR action potential detection at kilohertz imaging rates in mouse hippocampal slices, zebrafish larvae, and the cortex of awake mice, demonstrating high-contrast action potential detection under 2P illumination with rhodopsin-based GEVIs in vitro and in vivo.

Risk estimation is key for primary prevention of cardiovascular diseases (CVD). The European Society of Cardiology recommends SCORE2, SCORE2-OP (Older Persons), and SCORE2-Diabetes (collectively, the SCORE2 family-of-models (FOMs)) for 10-year CVD-risk estimation. As the COVID-19 pandemic was associated with higher CVD incidences, we externally validated the SCORE2-FOMs using contemporary nationwide data and assessed the need for adaptation.