A Direct Projection from Mouse Primary Visual Cortex to Dorsomedial Striatum

The mammalian striatum receives inputs from many cortical areas, but the existence of a direct axonal projection from the primary visual cortex (V1) is controversial. In this study we use anterograde and retrograde tracing techniques to demonstrate that V1 directly innervates a topographically defined longitudinal strip of dorsomedial striatum in mice. We find that this projection forms functional excitatory synapses with direct and indirect pathway striatal projection neurons (SPNs) and engages feed-forward inhibition onto these cells. Importantly, stimulation of V1 afferents is sufficient to evoke phasic firing in SPNs. These findings therefore identify a striatal region that is functionally innervated by V1 and suggest that early visual processing may play an important role in striatal-based behaviors

Dopaminergic neurons inhibit striatal output via non-canonical release of GABA

The substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) contain the two largest populations of dopamine (DA)-releasing neurons in the mammalian brain. These neurons extend elaborate projections in striatum, a large subcortical structure implicated in motor planning and reward-based learning. Phasic activation of dopaminergic neurons in response to salient or reward-predicting stimuli is thought to modulate striatal output via the release of DA to promote and reinforce motor action1–4. Here we show that activation of DA neurons in striatal slices rapidly inhibits action potential firing in both direct-and indirect-pathway striatal projection neurons (SPNs) through vesicular release of the inhibitory transmitter γ-aminobutyric acid (GABA). GABA is released directly from dopaminergic axons but in a manner that is independent of the vesicular GABA transporter VGAT. Instead GABA release requires activity of the vesicular monoamine transporter VMAT2, which is the vesicular transporter for DA. Furthermore, VMAT2 expression in GABAergic neurons lacking VGAT is sufficient to sustain GABA release. Thus, these findings expand the repertoire of synaptic mechanisms employed by DA neurons to influence basal ganglia circuits, reveal a novel substrate whose transport is dependent on VMAT2, and demonstrate that GABA can function as a bona fide co-transmitter in monoaminergic neurons

Midbrain dopamine neurons sustain inhibitory transmission using plasma membrane uptake of GABA, not synthesis

Synaptic transmission between midbrain dopamine neurons and target neurons in the striatum is essential for the selection and reinforcement of movements. Recent evidence indicates that nigrostriatal dopamine neurons inhibit striatal projection neurons by releasing a neurotransmitter that activates GABAA receptors. Here, we demonstrate that this phenomenon extends to mesolimbic afferents, and confirm that the released neurotransmitter is GABA. However, the GABA synthetic enzymes GAD65 and GAD67 are not detected in midbrain dopamine neurons. Instead, these cells express the membrane GABA transporters mGAT1 (Slc6a1) and mGAT4 (Slc6a11) and inhibition of these transporters prevents GABA co-release. These findings therefore indicate that GABA co-release is a general feature of midbrain dopaminergic neurons that relies on GABA uptake from the extracellular milieu as opposed to de novo synthesis. This atypical mechanism may confer dopaminergic neurons the flexibility to differentially control GABAergic transmission in a target-dependent manner across their extensive axonal arbors. DOI: http://dx.doi.org/10.7554/eLife.01936.00

Pathway-specific action of gamma-hydroxybutyric acid in sensory thalamus and its relevance to absence seizures

The systemic injection of -hydroxybutyric acid (GHB) elicits spike and wave discharges (SWDs), the EEG hallmark of absence seizures, and represents a well established, widely used pharmacological model of this nonconvulsive epilepsy. Despite this experimental use of GHB, as well as its therapeutic use in narcolepsy and its increasing abuse, however, the precise cellular mechanisms underlying the different pharmacological actions of this drug are still unclear. Because sensory thalamic nuclei play a key role in the generation of SWDs and sleep rhythms, and because direct injection of GHB in the ventrobasal (VB) thalamus elicits SWDs, we investigated GHB effects on corticothalamic EPSCs and GABAergic IPSCs in VB thalamocortical (TC) neurons. GHB (25

EuReCa ONE—27 Nations, ONE Europe, ONE Registry A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe

AbstractIntroductionThe aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.MethodsThis was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.ResultsData on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.ConclusionThe results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe.EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events

Dynamique spatio-temporelle et régulation de l'activité de la protéine kinase activée par l'adénosine monophosphate cyclique dans des préparations de neurones en tranche, et les mécanismes cellulaires d'action du GHB dans le thalamus ventrobasal

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Land use sustainability on the South-Eastern Amazon agricultural frontier: Recent progress and the challenges ahead

International audienceThe recent decoupling of deforestation and soybean production has raised optimistic expectations towards enhanced land use sustainability in the SouthEastern Amazon agricultural frontier. Nonetheless , assessing land use sustainability implies not only the consideration of how agricultural activities affect natural ecosystems but also how they impact on society and how society can cope with them. We review some of the forthcoming challenges that the agricultural sector should address to confirm its significant progress towards land use sustainability. Firstly, we assess the recent efforts to adopt environmentally friendly practices with regard to the ongoing intensification process mainly based on double cropping systems. Secondly, while rapid agricultural development has brought major social advances, we evidence a recent trend towards a decoupling of soy production and the Human Development Index at municipality level. We then put this result into perspective considering that the trend towards agricultural intensification based on the use of large amounts of agrochemicals could lead to major health concerns which are still too rarely considered. Finally, we discuss how the recent efficient policies to contain deforestation in the Amazon can cause indirect land use changes in the Brazilian Cerrados and in African Savannas, thus potentially leading to an "illusion of preservation" at global scale. We conclude that new indicators involving social sciences are necessary to better address the complexity of land use sustainability on the still very dynamic agricultural frontier in the SouthEastern Amazon

Data from: Acetylcholine waves and dopamine release in the striatum

<p>Striatal dopamine encodes reward, with recent work showing that dopamine release occurs in spatiotemporal waves. However, the mechanism of dopamine waves is unknown. Here we report that acetylcholine release in mouse striatum also exhibits wave activity, and that the spatial scale of striatal dopamine release is extended by nicotinic acetylcholine receptors. Based on these findings, and on our demonstration that single cholinergic interneurons can induce dopamine release, we hypothesized that the local reciprocal interaction between cholinergic interneurons and dopamine axons suffices to drive endogenous traveling waves. We show that the morphological and physiological properties of cholinergic interneuron – dopamine axon interactions can be modeled as a reaction-diffusion system that gives rise to traveling waves. Analytically-tractable versions of the model show that the structure and the nature of propagation of acetylcholine and dopamine traveling waves depend on their coupling, and that traveling waves can give rise to empirically observed correlations between these signals. Thus, our study provides evidence for striatal acetylcholine waves <em>in vivo</em>, and proposes a testable theoretical framework that predicts that the observed dopamine and acetylcholine waves are strongly coupled phenomena.</p><p>Funding provided by: International Human Frontier Science Program Organization<br>Crossref Funder Registry ID: https://ror.org/02ebx7v45<br>Award Number: RGP0062/2019</p><p>Funding provided by: European Research Council<br>Crossref Funder Registry ID: https://ror.org/0472cxd90<br>Award Number: 646886</p><p>Funding provided by: National Institutes of Health<br>Crossref Funder Registry ID: https://ror.org/01cwqze88<br>Award Number: DP2NS105553</p><p>Funding provided by: National Institutes of Health<br>Crossref Funder Registry ID: https://ror.org/01cwqze88<br>Award Number: R01MH130658</p><p>Funding provided by: Dana Foundation<br>Crossref Funder Registry ID: https://ror.org/01wt3vs82<br>Award Number: </p><p>Funding provided by: Whitehall Foundation<br>Crossref Funder Registry ID: https://ror.org/00her7k05<br>Award Number: </p&gt