Dopamine transmission is involved in reward processing and motor control, and its impairment plays a central role in numerous neurological disorders. Despite its strong pathophysiological relevance, the molecular and structural organization of the dopaminergic synapse remains to be established. Here, we used targeted labelling and fluorescence activated sorting to purify striatal dopaminergic synaptosomes. We provide the proteome of dopaminergic synapses with 57 proteins specifically enriched. Beyond canonical markers of dopamine neurotransmission such as dopamine biosynthetic enzymes and cognate receptors, we validated 6 proteins not previously described as enriched. Moreover, our data reveal the adhesion of dopaminergic synapses to glutamatergic, GABAergic or cholinergic synapses in structures we named “dopamine hub synapses”. At glutamatergic synapses, pre- and postsynaptic markers are significantly increased upon association with dopamine synapses. Dopamine hub synapses may thus support local dopaminergic signalling, complementing volume transmission thought to be the major mechanism by which monoamines modulate network activity. The neurotransmitter dopamine is an important regulator of brain function. Here the authors describe “dopamine hub synapses”, where dopamine transmission may act in synergy with other neurotransmitters.
Hardware performance monitoring counters have recently received a lot of attention. They have been used by diverse communities to understand and improve the quality of computing systems: for example, architects use them to extract application characteristics and propose new hardware mechanisms; compiler writers study how generated code behaves on particular hardware; software developers identify critical regions of their applications and evaluate design choices to select the best performing implementation. In this paper, we propose that counters be used by all categories of users, in particular non-experts, and we advocate that a few simple metrics derived from these counters are relevant and useful. For example, a low IPC (number of executed instructions per cycle) indicates that the hardware is not performing at its best; a high cache miss ratio can suggest several causes, such as conflicts between processes in a multicore environment. We also introduce a new simple and flexible user-level tool that collects these data on Linux platforms, and we illustrate its practical benefits through several use cases.
Every other week I explain basics in software testing, one of them is exploratory testing. It depends from group to group, but sometimes I have only 5-10 minutes on the topic. I love challenges! But I am also aware that I am still learning myself. This is why I asked my peers during Exploratory Testing…
Some people believe that nudges are an insult to human agency; that nudges are based on excessive trust in government; that nudges are covert; that nudges are m
The most critical intervention point to affect design at and across all physical scales (see graphic below) is to pay attention to the processes and patterns underlying their physical manifestations…
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