Functional diversity of midbrain dopamine (DA) neurons ranges across multiple scales, from differences in intrinsic properties and connectivity to selective task engagement in behaving animals. Distinct in vitro biophysical features of DA neurons have been associated with different axonal projection targets. However, it is unknown how this translates to different firing patterns of projection-defined DA subpopulations in the intact brain. We combined retrograde tracing with single-unit recording and labelling in mouse brain to create an in vivo functional topography of the midbrain DA system. We identified differences in burst firing among DA neurons projecting to dorsolateral striatum. Bursting also differentiated DA neurons in the medial substantia nigra (SN) projecting either to dorsal or ventral striatum. We found differences in mean firing rates and pause durations among ventral tegmental area (VTA) DA neurons projecting to lateral or medial shell of nucleus accumbens. Our data establishes a high-resolution functional in vivo landscape of midbrain DA neurons.

Purpose Based on findings of the Asian low-concentration atropine for myopia progression study, a concentration of 0.05% has been proposed as a good compromise between safety and efficacy for myopia control. However, no data on side effects have been published so far in Caucasian children receiving this dose. Methods Prior to commencement of bilateral atropine treatment with 0.05% atropine, 19 myopic children aged 5 to 15 years were treated in only one eye at bedtime leaving the other eye as a control. Pupil size, accommodation amplitude and near visual acuity were measured at 10:00 a.m. the next day and compared to the untreated contralateral control eye. The results were then compared to a cohort of 18 children whose treatment with 0.01% atropine commenced in a similar fashion. Results Twelve children (63%) reported visual impairment or reading difficulties. Anisocoria was 2.9 ± 1.1 mm. In comparison, 0.01% atropine led to a significantly less anisocoria of 0.8 ± 0.7 mm (p < 0.0001). Accommodation was decreased by − 4.2 ± 3.8 D in 0.05% atropine treated eyes, whereas 0.01% atropine induced hypoaccommodation of − 0.05 ± 2.5 D (p < 0.01). Near visual acuity was not significantly reduced in eyes treated with 0.05% atropine compared to 0.01% atropine (p = 0.26). Conclusion Compared to 0.01%, our data indicate stronger more relevant side effects of 0.05% topical atropine in young Caucasian children with progressive myopia as recently reported in Asian children, potentially compromising acceptance and compliance.

The firing activity of ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) dopaminergic (DA) neurons is an important factor in shaping DA release and its role in motivated behavior. Dendrites in DA neurons are the main postsynaptic compartment and, along with cell body and axon initial segment, contribute to action potential generation and firing pattern. In this study, the organization of the dendritic domain in individual VTA and SNc DA neurons of adult male mice, and their relationship to in vivo spontaneous firing, are described. In comparison with dorsal VTA DA neurons, ventrally located VTA neurons (as measured by cell body location) possess a shorter total dendritic length and simpler dendritic architecture, and exhibit the most irregular in vivo firing patterns among DA neurons. In contrast, for DA neurons in the SNc, the higher irregularity of firing was related to a smaller dendritic domain, as measured by convex hull volumes. However, firing properties were also related to the specific regional distribution of the dendritic tree. Thus, VTA DA neurons with a larger extension of their dendritic tree within the parabrachial pigmented (PBP) nucleus fired more regularly compared with those with relatively more dendrites extending outside the PBP. For DA neurons in the SNc, enhanced firing irregularity was associated with a smaller proportion of dendrites penetrating the substantia nigra pars reticulata. These results suggest that differences in dendritic morphology contribute to the in vivo firing properties of individual DA neurons, and that the existence of region-specific synaptic connectivity rules that shape firing diversity.

The low-threshold L-type calcium channel Ca v 1.3 accelerates the pacemaker rate in the heart, but its functional role for the extended dynamic range of neuronal firing is still unresolved. Here, we show that Ca v 1.3 calcium channels act as unexpectedly simple, full-range linear amplifiers of firing rates for lateral dopamine substantia nigra (DA SN) neurons in mice. This means that they boost in vitro or in vivo firing frequencies between 2 and 50 hertz by about 30%. Furthermore, we demonstrate that clinically relevant, low nanomolar concentrations of the L-type channel inhibitor isradipine selectively reduce the in vivo firing activity of these nigrostriatal DA SN neurons at therapeutic plasma concentrations. Thus, our study identifies the pacemaker function of neuronal Ca v 1.3 channels and provides direct evidence that repurposing dihydropyridines such as isradipine is feasible to selectively modulate the in vivo activity of highly vulnerable DA SN subpopulations in Parkinson’s disease.

Background To date, only four cases of ocular spiroplasma infection have been reported in the entire ophthalmic literature. We add two more cases to raise awareness of this sight-threatening congenital disease that manifests as cataract with ocular inflammation. Case presentation Both infants were referred for cataracts associated with ocular inflammation. Case 1, a 3-week-old neonate presented with unilateral cataract, ocular inflammation and elevated intraocular pressure. Case 2 was a 3-month-old infant with bilateral cataract and panuveitis. Lensectomies with or without vitrectomy and subsequent analyses of the specimens were performed. Transmission electron microscopy and multiplex polymerase chain reaction or 16 s rRNA gene polymerase chain reaction revealed spiroplasma species. Conclusions Spiroplasma as a very rare cause for congenital cataract might be underdiagnosed. We recommend performing polymerase chain reaction to probe for spiroplasma species in congenital cataracts with an inflammatory component.