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.

The dorsolateral striatum (DLS) receives excitatory inputs from both sensory and motor cortical regions. In the neocortex, sensory responses are affected by motor activity, however, it is not known whether such sensorimotor interactions occur in the striatum and how they are shaped by dopamine. To determine the impact of motor activity on striatal sensory processing, we performed in vivo whole-cell recordings in the DLS of awake mice during the presentation of tactile stimuli. Striatal medium spiny neurons (MSNs) were activated by both whisker stimulation and spontaneous whisking, however, their responses to whisker deflection during ongoing whisking were attenuated. Dopamine depletion reduced the representation of whisking in direct-pathway MSNs, but not in those of the indirect-pathway. Furthermore, dopamine depletion impaired the discrimination between ipsilateral and contralateral sensory stimulation in both direct and indirect pathway MSNs. Our results show that whisking affects sensory responses in DLS and that striatal representation of both processes is dopamine- and cell type-dependent.

Striatal cholinergic interneurons (CINs) can drive local dopamine release via nicotinic acetylcholine receptors (nAChRs) expressed on dopaminergic axons, but their role in modulating serotonin (5-HT) signaling is poorly understood. Here, we show that synchronous activation of CINs directly triggers local 5-HT release in the dorsal striatum via nAChRs expressed on serotonergic axons. This CIN-5-HT coupling is not detectable in the ventral striatum, despite its substantially denser serotonergic innervation. The nAChR-dependent release not only increases 5-HT levels in the dorsal striatum, but also expands the spatial footprint of serotonergic signaling. In Sapap3 mice, a model of obsessive-compulsive disorder (OCD)-like behavior, this mechanism is exaggerated due to a hypercholinergic state, selectively amplifying the nAChR-dependent component of monoamine release. These findings demonstrate a regionally confined form of acetylcholine-5-HT crosstalk in the striatum and identify CINs as regulators of 5-HT dynamics in both healthy and pathological states.

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.

This meta-analysis investigated the effects of yoga-based interventions on caregiver quality of life and psychosocial variables.

Screening for HIV and hepatitis C virus (HCV) are essential for identifying undiagnosed infections and linking individuals to care. We conducted a qualitative study to understand facilitators and barriers contributing to increased HIV and HCV infection screening and the linkage to care in Gilead's FOCUS HIV and HCV screening program in clinical settings. Individual in-depth interviews were conducted with nine clinical partners in FOCUS-supported sites and eight FOCUS regional leads who provided technical assistance to the sites. Content analysis was undertaken to identify key themes. Three themes emerged as facilitators: (a) "champions" to lead screening activities, (b) having support from clinic administrative leadership, and (c) coalescing staff support. Two themes emerged as barriers: (a) aligning institutional screening policies with local laws and (b) securing resources for screening implementation activities. Clinical settings implementing HIV or HCV infection screening programs may consider identifying a champion and consider legal and resource concerns to facilitate implementation of impactful programs.