SummaryDifferent striatal projection neurons are the origin of a dual organization essential for basal ganglia function. We have defined an analogous division of labor in the external globus pallidus (GPe) of Parkinsonian rats, showing that the distinct temporal activities of two populations of GPe neuron in vivo are underpinned by distinct molecular profiles and axonal connectivities. A first population of prototypic GABAergic GPe neurons fire antiphase to subthalamic nucleus (STN) neurons, often express parvalbumin, and target downstream basal ganglia nuclei, including STN. In contrast, a second population (arkypallidal neurons) fire in-phase with STN neurons, express preproenkephalin, and only innervate the striatum. This novel cell type provides the largest extrinsic GABAergic innervation of striatum, targeting both projection neurons and interneurons. We conclude that GPe exhibits several core components of a dichotomous organization as fundamental as that in striatum. Thus, two populations of GPe neuron together orchestrate activities across all basal ganglia nuclei in a cell-type-specific manner.

Objective: The impact on mood and memory of consuming a probiotic containing milk drink, or a placebo, was examined as, previously, a poor mood has been found to correlate with the frequency of constipation. Design: A double-blind placebo-controlled trial with random allocation of subjects. Setting: Subjects went about their normal life in the community apart from three visits to the laboratory. Subjects: One hundred and thirty-two healthy members of general population, mean age 61.8 years, volunteered in response to local media coverage. One hundred and twenty-four finished the trial. Intervention: For a 3-week period, either a probiotic containing milk drink, or a placebo, were consumed daily. Mood and cognition were measured at baseline, and after 10 and 20 days of consumption. Results: At baseline those who reported themselves to be less frequently constipated were more clearheaded, confident and elated. Although the taking of the probiotic did not generally change the mood, this appeared to be a reflection of the generally good mood in this sample. When those in the bottom third of the depressed/elated dimension at baseline were considered, they selectively responded by reporting themselves as happy rather than depressed after taking the probiotic. The intervention did not, however, influence the reported frequency of defaecation, probably a reflection of the initially low incidence of constipation. An unexpected and possibly chance finding was that the consumption of probiotics resulted in a slightly-poorer performance on two measures of memory. Conclusions: The consumption of a probiotic-containing yoghurt improved the mood of those whose mood was initially poor. This improvement in mood was not, however, associated with an increased frequency of defaecation. Sponsorship: Funded by Yakult, Japan.

Cannabis sativa has been used for recreational, therapeutic and other uses for thousands of years. The plant contains more than 120 C terpenophenolic constituents named phytocannabinoids. The Δ-tetrahydrocannabinol type class of phytocannabinoids comprises the largest proportion of the phytocannabinoid content. Δ-tetrahydrocannabinol was first discovered in 1971. This led to the discovery of the endocannabinoid system in mammals, including the cannabinoid receptors CB and CB. Δ-Tetrahydrocannabinol exerts its well-known psychotropic effects through the CB receptor but this effect of Δ-tetrahydrocannabinol has limited the use of cannabis medicinally, despite the therapeutic benefits of this phytocannabinoid. This has driven research into other targets outside the endocannabinoid system and has also driven research into the other non-psychotropic phytocannabinoids present in cannabis. This chapter presents an overview of the molecular pharmacology of the seven most thoroughly investigated phytocannabinoids, namely Δ-tetrahydrocannabinol, Δ-tetrahydrocannabivarin, cannabinol, cannabidiol, cannabidivarin, cannabigerol, and cannabichromene. The targets of these phytocannabinoids are defined both within the endocannabinoid system and beyond. The pharmacological effect of each individual phytocannabinoid is important in the overall therapeutic and recreational effect of cannabis and slight structural differences can elicit diverse and competing physiological effects. The proportion of each phytocannabinoid can be influenced by various factors such as growing conditions and extraction methods. It is therefore important to investigate the pharmacology of these seven phytocannabinoids further, and characterise the large number of other phytocannabinoids in order to better understand their contributions to the therapeutic and recreational effects claimed for the whole cannabis plant and its extracts.