A Selective Projection from the Subthalamic Nucleus to Parvalbumin-Expressing Interneurons of the Striatum.

The striatum and subthalamic nucleus (STN) are considered to be the primary input nuclei of the basal ganglia. Projection neurons of both striatum and STN can extensively interact with other basal ganglia nuclei, and there is growing anatomic evidence of direct axonal connections from the STN to striatum. There remains, however, a pressing need to elucidate the organization and impact of these subthalamostriatal projections in the context of the diverse cell types constituting the striatum. To address this, we conducted monosynaptic retrograde tracing from genetically-defined populations of dorsal striatal neurons in adult male and female mice, quantifying the connectivity from STN neurons to spiny projection neurons, GABAergic interneurons, and cholinergic interneurons. In parallel, we used a combination of ex vivo electrophysiology and optogenetics to characterize the responses of a complementary range of dorsal striatal neuron types to activation of STN axons. Our tracing studies showed that the connectivity from STN neurons to striatal parvalbumin-expressing interneurons is significantly higher (∼4- to 8-fold) than that from STN to any of the four other striatal cell types examined. In agreement, our recording experiments showed that parvalbumin-expressing interneurons, but not the other cell types tested, commonly exhibited robust monosynaptic excitatory responses to subthalamostriatal inputs. Taken together, our data collectively demonstrate that the subthalamostriatal projection is highly selective for target cell type. We conclude that glutamatergic STN neurons are positioned to directly and powerfully influence striatal activity dynamics by virtue of their enriched innervation of GABAergic parvalbumin-expressing interneurons.

Varsity Medical Ethics Debate 2015: should nootropic drugs be available under prescription on the NHS?

The 2015 Varsity Medical Ethics debate convened upon the motion: "This house believes nootropic drugs should be available under prescription". This annual debate between students from the Universities of Oxford and Cambridge, now in its seventh year, provided the starting point for arguments on the subject. The present article brings together and extends many of the arguments put forward during the debate. We explore the current usage of nootropic drugs, their safety and whether it would be beneficial to individuals and society as a whole for them to be available under prescription. The Varsity Medical Debate was first held in 2008 with the aim of allowing students to engage in discussion about ethics and policy within healthcare. The event is held annually and it is hoped that this will allow future leaders to voice a perspective on the arguments behind topics that will feature heavily in future healthcare and science policy. This year the Oxford University Medical Society at the Oxford Union hosted the debate.